Introduction - McMaster University - Abbott nutrition free ceu

Genetic diversity and the risk for dysglycemia Genetic diversity and the risk for dysglycemia: a study of South Asian and white Caucasian populations.ByZahra Naurish Sohani, B.H.Sc., M.Sc.A thesis submitted to the School of Graduate Studies in partial fulfilment of the requirements for the degree Doctor of PhilosophyDepartment of Clinical Epidemiology and BiostatisticsHealth Research Methodology ProgramMcMaster University ? Copyright by Zahra N. Sohani, June 2015DOCTOR OF PHILOSOPHY (2015)McMaster UniversityHamilton, Ontario, Canada(Department of Clinical Epidemiology and Biostatistics, Health Research Methodology Program)TITLE: Genetic diversity and the risk for dysglycemia: a study of South Asian and white Caucasian populations.AUTHOR: Zahra Naurish Sohani, B.H.Sc., M.Sc.SUPERVISOR: Dr. Sonia AnandNUMBER OF PAGES: xvi, 153AbstractBackground: Type 2 diabetes affects approximately 8% of the world’s population. Individuals of South Asian ancestry tend to develop metabolic abnormalities, leading to diabetes, at lower measures of absolute obesity and approximately 10 years earlier than white Caucasians. Current literature is unclear on the source of this ethnic heterogeneity; the variation in risk cannot be explained by lifestyle factors alone. The overarching aim of this thesis is to explore the role of genetic variants and epigenetic differences to explain the greater risk for type 2 diabetes among South Asians.Methods: We first conducted a systematic review of the literature to ascertain the genetic risk from known single nucleotide polymorphisms (SNPs) among South Asians. We then compared these risk estimates to those from white Caucasians in a cohort of 69,033 individuals. Second, using the EpiDREAM prospective cohort study of individuals at high-risk for diabetes, we assessed the impact of genetic burden for impaired pancreatic beta-cell function alone and together with abdominal obesity on glucose traits. Ethnic heterogeneity in this interaction was also studied. Lastly, using data from two Canadian birth cohorts of South Asian and white Caucasian ancestry, we investigated ethnic differences in the epigenetic architecture for genes known to be implicated birth weight and length, as both are associated with the future risk of adult diabetes. Results: The systematic review identified 15 SNPs robustly associated with type 2 diabetes in both South Asians and white Caucasians. The magnitude of risk and allele frequency of these genetic variants did not differ between the ethnic groups. Additionally, we identified 8 novel polymorphisms implicated in diabetes only among South Asians. Second, using data from the EpiDREAM study, we identified an interaction between cumulative genetic burden of beta-cell impairment, measured using an un-weighted genotype score, and abdominal obesity on glucose traits in South Asians, but not white Caucasians. Third, our investigation of differential DNA methylation between the ethnic groups revealed seven CpG sites for which changes in methylation corresponded to alterations in birth weight among white Caucasians, but not South Asians. An independent agnostic genome-wide search identified methylation levels at three CpG sites that appear to uniquely modulate birth weight in South Asians. Conclusions: Overall, our results indicate that the greater risk for metabolic traits in South Asians likely does not result from common genetic variants shared by both South Asians and white Caucasians. Rather, differences in risk may be additionally influenced by unique risk variants in South Asians. Furthermore, it appears that the risk from a genetic impairment in South Asians may be magnified by abdominal obesity.AcknowledgementsI would first and foremost like to sincerely thank my supervisor, Dr. Sonia Anand, for her mentorship, guidance, and support over the years. She has been an exceptional role model and has given me the confidence to explore my hypotheses and the tools to explore them well. I also thank her for extensively reviewing this thesis.To my committee members, Dr. Hertzel Gerstein, Dr. David Meyre, and Dr. Guillaume Paré, I extend my gratitude for their direction, patience, and feedback. Additionally, I thank Dr. Gerstein for his guidance and mentorship during my Comprehensive Exams. The systematic review included in this thesis would not have been possible without the substantial efforts and collaborative work of the co-authors, Wei Deng, Dr. Paré, Dr. Meyre, Dr. Gerstein, and Dr. Anand. Furthermore, I want to express my gratitude to the study teams at the Chanchalani Research Centre and Population Health Research Institute. Dr. Senay Asma, Dr. Philip Joseph, Dipika Desai, Dr. Sebastien Robiou-du-Pont, Natalie Campbell, Randa Stringer, Dr. Michael Zulyniak, and Dr. Russell de Souza, I thank you for coordinating and facilitating use of the study data, teaching me new skills, and patiently answering my many questions. I am grateful to the Canadian Diabetes Association and Ontario Graduate Scholarship program for providing me with funding to pursue my research. Additionally, I thank the faculty and students in the Department of Clinical Epidemiology & Biostatistics for enriching my learning. Most of all, I thank my parents, Naseem and Naushad, and siblings, Nida and Nauman, for their continuous and unconditional faith in me. And to Mandark, thank you for inspiring me to pursue my dreams and for your unwavering support in this pursuit.Table of Contents TOC \o "1-3" Chapter 1: Introduction PAGEREF _Toc301524387 \h 11.1 Overview of knowledge to date PAGEREF _Toc301524388 \h 11.2 Aims of this thesis PAGEREF _Toc301524389 \h 51.3 Potential impact PAGEREF _Toc301524390 \h 6Chapter 2: Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white Caucasian populations? PAGEREF _Toc301524391 \h 82.1 Background PAGEREF _Toc301524392 \h 92.2 Methods PAGEREF _Toc301524393 \h 92.2.1 Systematic review of studies assessing genetic risk of type 2 diabetes in South Asians PAGEREF _Toc301524394 \h 92.2.2 Comparison of meta-analysed SNPs in South Asians with white Caucasians PAGEREF _Toc301524395 \h 112.2.3 Testing novel SNPs discovered from South Asians GWA-studies in white Caucasians PAGEREF _Toc301524396 \h 122.3 Results PAGEREF _Toc301524397 \h 152.3.1 Systematic review and meta-analysis PAGEREF _Toc301524398 \h 152.3.2 Comparison of effect sizes, RAF, and risk alleles between South Asians and white Caucasians PAGEREF _Toc301524399 \h 172.3.3 Testing novel SNPs discovered from South Asian GWA-studies in white Caucasians PAGEREF _Toc301524400 \h 192.3.4 Population burden PAGEREF _Toc301524401 \h 222.4 Discussion PAGEREF _Toc301524402 \h 232.4.1 SNPs associated with type 2 diabetes from meta-analysis of South Asian studies PAGEREF _Toc301524403 \h 232.4.2 Comparison of effect sizes, RAF and risk alleles between South Asians and white Caucasians PAGEREF _Toc301524404 \h 242.4.3 Testing novel SNPs discovered from South Asians GWA-studies in white Caucasians PAGEREF _Toc301524405 \h 262.4.4 Population burden PAGEREF _Toc301524406 \h 272.4.5 Strengths and limitations PAGEREF _Toc301524407 \h 282.4.6 Future directions PAGEREF _Toc301524408 \h 292.5 Conclusions PAGEREF _Toc301524409 \h 29Chapter 3: Dysglycemia from genetic pancreatic beta-cell failure is worsened by abdominal obesity PAGEREF _Toc301524410 \h 313.1 Background PAGEREF _Toc301524411 \h 313.2 Methods PAGEREF _Toc301524412 \h 323.2.1 Participants PAGEREF _Toc301524413 \h 323.2.2 SNP selection and genotype score PAGEREF _Toc301524414 \h 333.2.3 Genotyping and sample quality control PAGEREF _Toc301524415 \h 343.2.4 Population structure and inbreeding PAGEREF _Toc301524416 \h 353.2.5 Matching PAGEREF _Toc301524417 \h 353.2.6 Outcomes PAGEREF _Toc301524418 \h 363.2.8 Statistical analyses PAGEREF _Toc301524419 \h 373.3 Results PAGEREF _Toc301524420 \h 373.3.1 Association of beta-cell genotype score with glucose traits PAGEREF _Toc301524421 \h 383.3.2 Ethnic heterogeneity in interaction of beta-cell genotype score with abdominal obesity PAGEREF _Toc301524422 \h 403.3.3 Population structure and inbreeding PAGEREF _Toc301524423 \h 413.4 Discussion PAGEREF _Toc301524424 \h 413.4.1 Association of beta-cell genotype score with glucose traits PAGEREF _Toc301524425 \h 413.4.2 Ethnic heterogeneity in interaction of beta-cell genotype score with abdominal obesity PAGEREF _Toc301524426 \h 433.4.3 Population stratification and inbreeding PAGEREF _Toc301524427 \h 443.4.4 Strengths and limitations PAGEREF _Toc301524428 \h 453.5 Conclusions PAGEREF _Toc301524429 \h 46Chapter 4: Ethnic heterogeneity in DNA Methylation for birth weight and length PAGEREF _Toc301524430 \h 474.1 Background PAGEREF _Toc301524431 \h 474.2 Methods PAGEREF _Toc301524432 \h 494.2.1 Participants PAGEREF _Toc301524433 \h 494.2.3 Quality control procedures PAGEREF _Toc301524434 \h 494.2.4 Ethnic heterogeneity in methylation of known birth weight and length genes PAGEREF _Toc301524435 \h 514.2.5 Regional analysis of significant sites PAGEREF _Toc301524436 \h 544.2.6 Genome-wide methylation for birth weight in South Asians PAGEREF _Toc301524437 \h 544.3 Results PAGEREF _Toc301524438 \h 554.3.1 Ethnic heterogeneity in methylation at known birth weight and length genes PAGEREF _Toc301524439 \h 564.3.2 Regional analysis of significant sites PAGEREF _Toc301524440 \h 654.3.3 Genome-wide methylation for birth weight in South Asians PAGEREF _Toc301524441 \h 674.4 Discussion PAGEREF _Toc301524442 \h 694.4.1 Ethnic heterogeneity in methylation at known birth weight genes PAGEREF _Toc301524443 \h 704.4.3 Regional analysis of significant sites PAGEREF _Toc301524444 \h 724.3.4 Genome-wide methylation for birth weight in South Asians PAGEREF _Toc301524445 \h 734.4.5 Strengths and limitations PAGEREF _Toc301524446 \h 744.5 Conclusions PAGEREF _Toc301524447 \h 75Chapter 5: Discussion PAGEREF _Toc301524448 \h 765.1 Overview of findings PAGEREF _Toc301524449 \h 765.2 Methodological considerations PAGEREF _Toc301524450 \h 795.2.1 Internal validity PAGEREF _Toc301524451 \h 795.2.2 External validity PAGEREF _Toc301524452 \h 865.3 Other considerations for trans-ethnic genetic studies PAGEREF _Toc301524453 \h 875.3.1 Population stratification PAGEREF _Toc301524454 \h 875.3.2 Linkage disequilibrium PAGEREF _Toc301524455 \h 885.4 Future directions and Conclusions PAGEREF _Toc301524456 \h 89References PAGEREF _Toc301524457 \h 90Appendices PAGEREF _Toc301524458 \h 115List of FiguresChapter 1: No figures.Chapter 2: TOC \c "Figure" Figure 2.1 Overview of the study design PAGEREF _Toc301524459 \h 13Figure 2.2 Flow diagram of the systematic review of South Asian literature investigating genetic variants predisposing to type 2 diabetes PAGEREF _Toc301524460 \h 14Figure 2.3 Forest plot of SNPs associated with type 2 diabetes in South Asians from systematic review and white Caucasians from DIAGRAM. Chr: Chromosome; RAF: risk allele frequency; P het: P-value for heterogeneity. SNPs are ordered by level of significance in South Asian meta-analysis. PAGEREF _Toc301524461 \h 18Figure 2.4 Venn diagram of SNPs common to South Asians and white Caucasians and SNPs unique to both groups. CENTD2 is also known as ARAP1; TMEM195 is also known as AGMO. The green box includes genes with GWAS evidence for association with type 2 diabetes; the pink box includes genes with GWAS evidence in whites and association with type 2 diabetes in this meta-analysis; and yellow with genes identified from a trans-ethnic meta-analysis of South Asians and white Caucasians. PAGEREF _Toc301524462 \h 19Figure 2.5 Genotype score (with 95% confidence intervals) of SNPs in South Asians and white Caucasians. The genotype score was constructed using effect estimates and RAFs from SNPs common to both groups PAGEREF _Toc301524463 \h 22Chapter 3: TOC \c "Figure 3.1" Figure 3.1 Criteria for selection and inclusion of SNPs implicated in beta-cell function PAGEREF _Toc301524464 \h 34Figure 3.2 Interaction between beta-cell genotype score and abdominal obesity stratified by ethnic group PAGEREF _Toc301524465 \h 40Chapter 4: TOC \c "Figure 4." Figure 4.1 Plots of Pearson’s r correlations for CpG sites on TCF7L2 and CALCR in white Caucasians and South Asians PAGEREF _Toc301524466 \h 66Figure 4.2 Manhattan plot showing the distribution of P values of the association between methylation probes and birth weight in South Asians PAGEREF _Toc301524467 \h 68Figure 4.3 Q-Q plot of P-values acquired from GWA-studies of CpG sites PAGEREF _Toc301524468 \h 69Chapter 5: TOC \c "Figure 5." Figure 5.1 Power calculations for case-control association studies of unrelated individuals. Curves represent the number of individuals, at a case-control ratio of 1:1, required to achieve 80% power for a disease prevalence of 10% at α = 0.05. PAGEREF _Toc301522691 \h 83List of TablesChapter 1: No Tables.Chapter 2: TOC \c "Table 2." Table 2.1 Comparison of SNPs discovered from South Asian GWA-studies with white Caucasian estimates from the DIAGRAM Consortium PAGEREF _Toc301524469 \h 21Table 2.2 SNPs associated with type 2 diabetes in published GWA-studies from white Caucasians but not replicated in South Asian meta-analysis PAGEREF _Toc301524470 \h 25Chapter 3: TOC \c "Table 3." Table 3.1 Summary characteristics of included participants from the EpiDREAM cohort PAGEREF _Toc301524471 \h 39Table 3.2 Effect of the genotype score on glucose traits stratified by ethnicity PAGEREF _Toc301524472 \h 39Chapter 4: TOC \c "Table 4." Table 4.1 Descriptive characteristics of included participants stratified by ethnicity PAGEREF _Toc301524484 \h 56Table 4.2 Association between percent methylation at sites showing ethnic variation for birth weight in cord-blood DNA PAGEREF _Toc301524485 \h 58Table 4.3 Percent methylation at the seven sites showing ethnic heterogeneity in the primary analysis PAGEREF _Toc301524486 \h 59Table 4.4 Association between methylation level and SNP on birth weight genes PAGEREF _Toc301524487 \h 64Table 4.5 Regional analysis of significant CpG sites in South Asians and white Caucasians PAGEREF _Toc301524488 \h 67Table 4.6 Association between percent methylation on CpG sites associated at P<1x10-5 with birth weight in South Asians PAGEREF _Toc301524489 \h 68Chapter 5: No Tables.List of AppendicesChapter 1: No appendices.Chapter 2: TOC \c "Supplementary Table 2." Supplementary Table 2.1 Full search strategy for systematic review PAGEREF _Toc301524494 \h 115Supplementary Table 2.2 Reported SNPs and their proxies in LD (r2 > 0.8) determined using SNAP PAGEREF _Toc301524495 \h 117Supplementary Table 2.3 Characteristics of studies included in the systematic review PAGEREF _Toc301524496 \h 118Supplementary Table 2.4 Risk of bias assessment for studies included in the systematic review PAGEREF _Toc301524497 \h 124Chapter 3: TOC \c "Supplementary Table 3." Supplementary Table 3.1 Risk allele frequencies and HWE-P values for SNPs available in the EpiDREAM cohort PAGEREF _Toc301524505 \h 132Supplementary Table 3.2 Effect of 11 SNPs included in the genotype score on fasting glucose from GWA-studies PAGEREF _Toc301524506 \h 133 TOC \c "Supplementary Figure 3." Supplementary Figure 3.1 Histograms of AUC glucose (a) and fasting glucose (b) PAGEREF _Toc301524658 \h 135Supplementary Figure 3.2 First three principle components for (a) South Asians and (b) white Caucasians PAGEREF _Toc301524659 \h 136Supplementary Figure 3.3 Histogram of Inbreeding coefficients in (a) South Asians and (b) white Caucasians PAGEREF _Toc301524660 \h 138Chapter 4: TOC \c "Supplementary Table 4." Supplementary Table 4.1 Inclusion and exclusion criteria for the START and CHILD cohorts PAGEREF _Toc301524511 \h 140Supplementary Table 4.2 Allele frequencies and HWE-P values for SNPs available in the START and CHILD cohorts. PAGEREF _Toc301524512 \h 141Supplementary Table 4.3 Genes (and SNPs) chosen for investigation in the primary analysis from a literature search PAGEREF _Toc301524513 \h 142Supplementary Table 4.4 Global methylation differences between START and CHILD cohorts PAGEREF _Toc301524514 \h 143Supplementary Table 4.5 SNP associations for birth weight genes in South Asians and white Caucasian newborns PAGEREF _Toc301524515 \h 144Supplementary Table 4.6 SNP associations for birth length genes in South Asian and white Caucasian newborns PAGEREF _Toc301524516 \h 145Supplementary Table 4.7 Overview of key differences in blood collection protocols of the START and CHILD cohorts PAGEREF _Toc301524517 \h 146Supplementary Table 4.8 Variation in leukocyte and erythrocyte cell type composition between South Asians and white Caucasians from the CHILD cohort PAGEREF _Toc301524518 \h 147Supplementary Table 4.9 Association between CpG sites showing ethnic heterogeneity for birth weight in South Asians from the CHILD cohort (n=18) PAGEREF _Toc301524519 \h 148Supplementary Table 4.10 Effect of processing time on methylation level in the CHILD cohort PAGEREF _Toc301524520 \h 149Supplementary Table 4.11 Effect of processing time on methylation level in the CHILD cohort PAGEREF _Toc301524521 \h 150Supplementary Table 4.12 Percent of variance explained by clinical variables and CpG sites on birth weight in white Caucasians PAGEREF _Toc301524522 \h 151 TOC \c "Supplementary Figure 4." Supplementary Figure 4.1 Histograms of birth weight in South Asians (a) and white Caucasians (b); birth length in South Asians (c) and and fasting glucose (d) PAGEREF _Toc301524603 \h 152Chapter 5: No appendices.List of Abbreviations2hGluTwo hour GlucoseAFAllele FrequencyAGENAsian Genetic Epidemiology Network Type 2 DiabetesAUCArea Under CurveBMIBody Mass IndexCGICpG IslandChr.ChromosomeCHILDCaucasian newborns from the Canadian Healthy Infant Longitudinal DevelopmentCpGCytosine – Guanine dinucleotideDIAGRAMDIAbetes Genetics Replication And Meta-analysisDNADeoxyribo-Nucleic AcidDSATDeep Subcutaneous Adipose TissueEpiDREAMEpi-Diabetes REduction Assessment With Ramipril and Rosiglitazone MedicationFDRFalse Discovery RateFPGFasting Plasma GlucoseGWAGenome Wide AssociationHCHip CircumferenceHOMAHomeostatic Model of AssessmentHWEHardy-Weinberg EquilibriumICAM-1Intercellular Adhesion Molecule-1 IFGImpaired Fasting GlucoseIGTImpaired Glucose ToleranceLBWLow Birth WeightLDLinkage DisequilibriumMAGICMeta-Analyses of Glucose and Insulin-related traits ConsortiumMRIMagnetic Resonance ImagingNGTNormal Glucose ToleranceODIOral Disposition IndexOGTTOral Glucose Tolerance TestOROdds RatioRAFRisk Allele FrequencySAT2DSouth Asian Type 2 DiabetesSDStandard DeviationSNPSingle Nucleotide PolymorphismSSATSuperficial Subcutaneous Adipose TissueSTARTSouth Asian Birth Cohort SVDSingular Value DecompositionSWANSubset-quantile Within Array Normalization VATVisceral Adipose TissueWaistadjHipWaist Adjusted for HipWCWaist Circumference Declaration of Academic AchievementI am the primary author of the material included in this thesis. I contributed substantially to each chapter by taking a lead role in the conception, development, and analysis of the work discussed herein. Drs. Anand, Gerstein, Meyre, and Paré supervised me in the completion of this work. Lastly, contributions of co-authors for published work have been included as a note in the relevant chapters.Chapter 1Introduction1.1 Overview of knowledge to date1.1.1 Pathophysiology of diabetesType 2 diabetes is a heterogeneous disorder that affects approximately 8% of the world’s populationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "World Health Organization", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "publisher-place" : "Geneva, Switzerland", "title" : "Global status report on noncommunicable diseases 2014", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "1", "plainTextFormattedCitation" : "1", "previouslyFormattedCitation" : "1" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1. A triad of metabolic defects characterizes this disease: impairment in insulin secretion, ineffective sensitivity to insulin, and an increase in glucose production by the liver. While the specific contribution of each, and the primary defect needed for the development of type 2 diabetes is the subject of research and debate, it appears that overt diabetes is preceded by failure of the pancreatic beta-cells to compensate for ineffective insulin actionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(05)61032-X", "ISSN" : "1474-547X", "PMID" : "15823385", "abstract" : "Type 2 diabetes mellitus has become an epidemic, and virtually no physician is without patients who have the disease. Whereas insulin insensitivity is an early phenomenon partly related to obesity, pancreas beta-cell function declines gradually over time already before the onset of clinical hyperglycaemia. Several mechanisms have been proposed, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction for insulin resistance, and glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction. Moreover, the disease has a strong genetic component, but only a handful of genes have been identified so far: genes for calpain 10, potassium inward-rectifier 6.2, peroxisome proliferator-activated receptor gamma, insulin receptor substrate-1, and others. Management includes not only diet and exercise, but also combinations of anti-hyperglycaemic drug treatment with lipid-lowering, antihypertensive, and anti platelet therapy.", "author" : [ { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldstein", "given" : "Barry J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haeften", "given" : "Timon W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9467", "issued" : { "date-parts" : [ [ "0" ] ] }, "page" : "1333-46", "title" : "Type 2 diabetes: principles of pathogenesis and therapy.", "type" : "article-journal", "volume" : "365" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00125-002-1009-0", "ISSN" : "0012-186X", "PMID" : "12637977", "abstract" : "The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes have been debated extensively. The concept that a feedback loop governs the interaction of the insulin-sensitive tissues and the beta cell as well as the elucidation of the hyperbolic relationship between insulin sensitivity and insulin secretion explains why insulin-resistant subjects exhibit markedly increased insulin responses while those who are insulin-sensitive have low responses. Consideration of this hyperbolic relationship has helped identify the critical role of beta-cell dysfunction in the development of Type 2 diabetes and the demonstration of reduced beta-cell function in high risk subjects. Furthermore, assessments in a number of ethnic groups emphasise that beta-cell function is a major determinant of oral glucose tolerance in subjects with normal and reduced glucose tolerance and that in all populations the progression from normal to impaired glucose tolerance and subsequently to Type 2 diabetes is associated with declining insulin sensitivity and beta-cell function. The genetic and molecular basis for these reductions in insulin sensitivity and beta-cell function are not fully understood but it does seem that body-fat distribution and especially intra-abdominal fat are major determinants of insulin resistance while reductions in beta-cell mass contribute to beta-cell dysfunction. Based on our greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes, we can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Kahn", "given" : "S E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2003", "1" ] ] }, "page" : "3-19", "title" : "The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "2,3", "plainTextFormattedCitation" : "2,3", "previouslyFormattedCitation" : "2,3" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2,3. Reduced insulin secretion may be due to genetically mediated beta-cell dysfunction or result from hypothesized damage to the beta-cell from chronic exposure to hyperglycemia and/or free fatty acids. Under normal conditions, presence of insulin in the blood suppresses glucose secretion from the liver. However, with declining insulin levels, this suppression is inhibited, and in turn leads to hepatic glucose production, continuing to worsen dysglycemia in the course of diabetesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0149-5992", "PMID" : "11194248", "abstract" : "OBJECTIVE: Although prospective studies indicate that insulin resistance and insulin secretory dysfunction predict type 2 diabetes, they provide limited information on the relative contributions of both abnormalities to worsening glucose tolerance at different developmental stages of the disease. We therefore assessed the predictive effect of insulin resistance and insulin secretory dysfunction separately for the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and from IGT to diabetes.\n\nRESEARCH DESIGN AND METHODS: Insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp), acute insulin secretory response (AIR) (25-g intravenous glucose tolerance test), and body composition (hydrodensitometry or dual-energy X-ray absorptiometry) were measured in 254 Pima Indians with NGT and in 145 Pima Indians with IGT, who were then followed for 0.5-13 years.\n\nRESULTS: After follow-ups of 4.4 +/- 3.1 and 5.5 +/- 3.4 years, 79 (31%) of the subjects with initial NGT had developed IGT, and 64 (44%) of the subjects with initial IGT had developed diabetes. In proportional-hazards analyses with adjustment for age, sex, and percent body fat, low M and low AIR were independent predictors of both the progression from NGT to IGT (relative hazards [95% CI] for 10th vs. 90th percentile: M 2.4 [1.2-4.7], P < 0.02; AIR 2.1 [1.1-4.1], P < 0.04) and from IGT to diabetes (M 2.5 [1.3-5.0], P < 0.01; AIR 1.8 [0.99-3.3], P = 0.055).\n\nCONCLUSIONS: During each stage of the development of type 2 diabetes, insulin resistance and insulin secretory dysfunction are independent predictors of worsening glucose tolerance and are, therefore, both targets for the primary prevention of the disease.", "author" : [ { "dropping-particle" : "", "family" : "Weyer", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tataranni", "given" : "P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bogardus", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pratley", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2001", "1" ] ] }, "page" : "89-94", "title" : "Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00125-002-1009-0", "ISSN" : "0012-186X", "PMID" : "12637977", "abstract" : "The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes have been debated extensively. The concept that a feedback loop governs the interaction of the insulin-sensitive tissues and the beta cell as well as the elucidation of the hyperbolic relationship between insulin sensitivity and insulin secretion explains why insulin-resistant subjects exhibit markedly increased insulin responses while those who are insulin-sensitive have low responses. Consideration of this hyperbolic relationship has helped identify the critical role of beta-cell dysfunction in the development of Type 2 diabetes and the demonstration of reduced beta-cell function in high risk subjects. Furthermore, assessments in a number of ethnic groups emphasise that beta-cell function is a major determinant of oral glucose tolerance in subjects with normal and reduced glucose tolerance and that in all populations the progression from normal to impaired glucose tolerance and subsequently to Type 2 diabetes is associated with declining insulin sensitivity and beta-cell function. The genetic and molecular basis for these reductions in insulin sensitivity and beta-cell function are not fully understood but it does seem that body-fat distribution and especially intra-abdominal fat are major determinants of insulin resistance while reductions in beta-cell mass contribute to beta-cell dysfunction. Based on our greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes, we can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Kahn", "given" : "S E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2003", "1" ] ] }, "page" : "3-19", "title" : "The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/S0140-6736(05)61032-X", "ISSN" : "1474-547X", "PMID" : "15823385", "abstract" : "Type 2 diabetes mellitus has become an epidemic, and virtually no physician is without patients who have the disease. Whereas insulin insensitivity is an early phenomenon partly related to obesity, pancreas beta-cell function declines gradually over time already before the onset of clinical hyperglycaemia. Several mechanisms have been proposed, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction for insulin resistance, and glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction. Moreover, the disease has a strong genetic component, but only a handful of genes have been identified so far: genes for calpain 10, potassium inward-rectifier 6.2, peroxisome proliferator-activated receptor gamma, insulin receptor substrate-1, and others. Management includes not only diet and exercise, but also combinations of anti-hyperglycaemic drug treatment with lipid-lowering, antihypertensive, and anti platelet therapy.", "author" : [ { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldstein", "given" : "Barry J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haeften", "given" : "Timon W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-3", "issue" : "9467", "issued" : { "date-parts" : [ [ "0" ] ] }, "page" : "1333-46", "title" : "Type 2 diabetes: principles of pathogenesis and therapy.", "type" : "article-journal", "volume" : "365" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "2\u20134", "plainTextFormattedCitation" : "2\u20134", "previouslyFormattedCitation" : "2\u20134" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2–4. 1.1.2 Genetic basis of the diseaseAlthough type 2 diabetes is typically discussed as a product of obesity-prone lifestyles, the disease has a genetic basis. Family studies show that as high as 69% of the trait is attributed to genetic factors2. Additionally, Elbein et al. examined the heritability of beta-cell function, assessed as insulin response relative to sensitivity, and found heritability of this trait to be 67% in 120 participants who had either impaired glucose tolerance (IGT) or normal glucose tolerance (NGT). This estimate increased to 70% when only participants with IGT were consideredADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jcem.84.4.5604", "ISSN" : "0021-972X", "PMID" : "10199785", "abstract" : "Both defective insulin secretion and insulin resistance have been reported in relatives of type 2 diabetic subjects. We tested 120 members of 26 families with a type 2 diabetic sibling pair with a tolbutamide-modified, frequently sampled i.v. glucose tolerance test to determine the insulin sensitivity index (S(I)) and acute insulin response to glucose (AIRglucose). A measure of beta-cell compensation for insulin sensitivity was calculated as the product S(I) x AIRglucose, based on the demonstrated hyperbolic relationship between insulin sensitivity and insulin secretion. A percentile score for this compensation was assigned based on published values. Of the 120 family members, 26 had previously diagnosed impaired glucose tolerance on oral testing, and 94 had normal glucose tolerance tests. As a group, family members showed a significantly lower S(I) x AIRglucose than a similar, previously reported, control population, even when impaired glucose tolerance members were excluded. We performed a multivariate analysis of diabetes status, S(I), AIRglucose and to estimate the heritability of each trait and the genetic and environmental correlations between traits. We estimated the heritability of S(I) x AIRglucose to be 67 +/- 3% when all members were included and 70 +/- 4% when only normal glucose tolerance members were considered. Both AIRglucose and S(I) were also familial, albeit with lower heritabilities (38 +/- 1% and 38 +/- 2%, respectively, for all family members). Both S(I) x AIRglucose and S(I) showed strong negative genetic correlations with diabetes (-85 +/- 3% and -87 +/- 2%, respectively, all family members), whereas AIRglucose did not correlate with diabetes. We conclude that insulin secretion, as measured by S(I) x AIRglucose, is decreased in nondiabetic members of familial type 2 diabetic kindreds, that S(I) x AIRglucose in these high risk families is highly heritable, and that the same polygenes may determine diabetes status and a low S(I) x AIRglucose. Our data suggest that insulin secretion, when expressed as an index normalized for insulin sensitivity, is more familial than either insulin sensitivity or first phase insulin secretion alone and may be a very useful trait for identifying genetic predisposition to type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Elbein", "given" : "S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasstedt", "given" : "S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wegner", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "S E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1999", "4" ] ] }, "page" : "1398-403", "title" : "Heritability of pancreatic beta-cell function among nondiabetic members of Caucasian familial type 2 diabetic kindreds.", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "5", "plainTextFormattedCitation" : "5", "previouslyFormattedCitation" : "5" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }5. Lastly, heritability estimates for fasting plasma glucose (FPG) range from 38% to 51% according to studies of twins between 18 and 67 years of ageADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-003-1165-x", "ISSN" : "0012-186X", "PMID" : "12898014", "abstract" : "AIMS/HYPOTHESIS: Family and twin studies have reported different estimates of the relative contribution of genetic and environmental factors to the quantitative traits glucose tolerance, insulin secretion, and insulin sensitivity. Our aims were to estimate these relative influences in a large sample of twins from the population and to assess the effect of age.\n\nMETHODS: In this population-based, cross-sectional study we gave an oral glucose tolerance test to 317 women and 290 men who were same-sex healthy twin pairs between 18 to 67 years of age. The genetic, common environmental and individual environmental variance components for fasting and 120-min glucose and for fasting and 30-min insulin as well as the linear effects of age on these components were estimated by multivariate analysis (using the software FISHER).\n\nRESULTS: In women and men the heritability for fasting glucose was 12 and 38%, for 120-min glucose it was 38 and 43%, for fasting insulin it was 54 and 37%, and for 30-min insulin it was 57 and 47%, respectively. Under the assumption of no non-additive genetic effects (no intra- or inter-gene interaction) there was no strong evidence for common environmental effects, barring significant effects for fasting glucose in women. Heritability decreased with age for 120-min glucose in women and fasting insulin in men, whereas it increased for 120-min glucose in men.\n\nCONCLUSION/INTERPRETATION: This study indicates a limited additive genetic influence on the result of an OGTT, possibly with sex-specific age effects, and generally little or no influence of the common environment. Accordingly, there is a considerable individual environmental variation.", "author" : [ { "dropping-particle" : "", "family" : "Schousboe", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visscher", "given" : "P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henriksen", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopper", "given" : "J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "T I A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "K O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "1276-83", "title" : "Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2004-2471", "ISSN" : "0021-972X", "PMID" : "15728197", "abstract" : "The aim of this study was to evaluate genetic and environmental effects on plasma glucose, insulin secretion, and resistance in Finnish twins. Altogether 151 randomly selected twin pairs were examined by the oral glucose tolerance test; 66 twin pairs were monozygotic and 85 like-sexed dizygotic. We estimated the intraclass correlation coefficients and variance components of genetic and environmental effects on waist circumference, plasma glucose, and serum insulin. For fasting insulin, the proportion of total variation accounted for by additive genetic effects (A) and nonshared environmental effects (E) were 43 and 57%, respectively. As to postchallenge insulin and waist circumference, A effects were stronger in female twins (51 and 70%, respectively) than male twins in whom no significant evidence for genetic variance was found. Of the variation in fasting glucose, A and E effects accounted for 45 and 55%, respectively. Of the variation in postchallenge glucose, E effects had a greater role (65%), compared with A effects (35%); A effects on pre- and postchallenge insulin levels were highly correlated (genetic correlation coefficient = 0.81). In conclusion, additive genetic effects are important for the insulin secretion, whereas nonshared environmental effects contribute strongly to peripheral insulin resistance.", "author" : [ { "dropping-particle" : "", "family" : "Katoh", "given" : "Shuichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtovirta", "given" : "Mikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harjutsalo", "given" : "Valma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskenvuo", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tajima", "given" : "Naoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "5", "2" ] ] }, "language" : "en", "page" : "2642-7", "publisher" : "Endocrine Society", "title" : "Genetic and environmental effects on fasting and postchallenge plasma glucose and serum insulin values in Finnish twins.", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "6,7", "plainTextFormattedCitation" : "6,7", "previouslyFormattedCitation" : "6,7" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }6,7. Genome wide association (GWA) studies investigating genetic origins of type 2 diabetes have found around 100 base pair polymorphisms in the DNA (single nucleotide polymorphisms; SNPs) to date. Similarly, 43 SNPs have been implicated in fasting glucoseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2385", "ISSN" : "1546-1718", "PMID" : "22885924", "abstract" : "Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.", "author" : [ { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "Ryan P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montasser", "given" : "May E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gustafsson", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasmussen-Torvik", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shungin", "given" : "Dmitry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sidore", "given" : "Carlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Paul C D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jukema", "given" : "J Wouter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verweij", "given" : "Niek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Smith", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salo", "given" : "Perttu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pourcain", "given" : "Beate St", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Jeanette S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bielak", "given" : "Lawrence F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horikoshi", "given" : "Momoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isaacs", "given" : "Aaron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esko", "given" : "T\u00f5nu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mihailov", "given" : "Evelin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraser", "given" : "Ross M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fall", "given" : "Tove", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beckmann", "given" : "Jacques S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willems", "given" : "Sara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Hyun Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller-Nurasyid", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franco-Cereceda", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Folkersen", "given" : "Lasse", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marullo", "given" : "Letizia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jansen", "given" : "Hanneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oldehinkel", "given" : "Albertine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruinenberg", "given" : "Marcel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edkins", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Varga", "given" : "Tibor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oksa", "given" : "Heikki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antonella", "given" : "Mulas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagaraja", "given" : "Ramaiah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trompet", "given" : "Stella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ford", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Stephan J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munroe", "given" : "Patricia B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Antti", "given" : "Jula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miljkovic", "given" : "Iva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yongmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiess", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Alan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smit", "given" : "Johannes H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitriou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bolton", "given" : "Jennifer L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fowkes", "given" : "Gerard R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindstr\u00f6m", "given" : "Jaana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zemunik", "given" : "Tatijana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandinelli", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Basart", "given" : "Hanneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maerz", "given" : "Winfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kleber", "given" : "Marcus E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hastie", "given" : "Nicholas D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farrall", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hovingh", "given" : "G Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metspalu", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uusitupa", "given" : "Matti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Jackie F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Toenjes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peyser", "given" : "Patricia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6rner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter E H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adair", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Tim D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudnason", "given" : "Vilmundur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harst", "given" : "Pim", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sattar", "given" : "Naveed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Tamara B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cucca", "given" : "Francesco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teslovich", "given" : "Tanya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "page" : "991-1005", "title" : "Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.2274", "ISSN" : "1546-1718", "PMID" : "22581228", "abstract" : "Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and \u03b2-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 \u00d7 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.", "author" : [ { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hivert", "given" : "Marie-France", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grimsby", "given" : "Jonna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bielak", "given" : "Lawrence F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amin", "given" : "Najaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnes", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cadby", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladenvall", "given" : "Claes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lahti", "given" : "Jari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yongmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martinez-Larrad", "given" : "Maria Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montasser", "given" : "May E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasmussen-Torvik", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salo", "given" : "Perttu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sattar", "given" : "Naveed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shungin", "given" : "Dmitry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrade", "given" : "Mariza", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Jeanette S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aspelund", "given" : "Thor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandinelli", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beckmann", "given" : "Jacques S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellis", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blangero", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boban", "given" : "Mladen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouchard", "given" : "Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budimir", "given" : "Danijela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlson", "given" : "Olga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corbat\u00f3n-Anchuelo", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitriou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiriksdottir", "given" : "Gudny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eury", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ford", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudnason", "given" : "Vilmundur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansson", "given" : "Ola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Tamara B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jhun", "given" : "Min A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Paul C D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jukema", "given" : "J Wouter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kardia", "given" : "Sharon L R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolcic", "given" : "Ivana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lannfelt", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launer", "given" : "Lenore J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leander", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Guo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindstrom", "given" : "Jaana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miljkovic", "given" : "Iva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeff", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Ken K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palotie", "given" : "Aarno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pehlic", "given" : "Marina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pericic", "given" : "Marijana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perusse", "given" : "Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peyser", "given" : "Patricia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00e4ikk\u00f6nen", "given" : "Katri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sabater-Lleal", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Savage", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-Rios", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smit", "given" : "Johannes H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Albert Vernon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stan\u010d\u00e1kov\u00e1", "given" : "Alena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Sun", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trompet", "given" : "Stella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uusitupa", "given" : "Matti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vikstr\u00f6m", "given" : "Max", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vohl", "given" : "Marie-Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "Gerard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Widen", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willems", "given" : "Sara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jacqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yaghootkar", "given" : "Hanieh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zemunik", "given" : "Tatijana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zgaga", "given" : "Lina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "7" ] ] }, "page" : "659-69", "title" : "A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/ng.520", "ISSN" : "1546-1718", "PMID" : "20081858", "abstract" : "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henneman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dehghan", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lajunen", "given" : "Taina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabena", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sethupathy", "given" : "Praveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariyurek", "given" : "Yavuz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barter", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochud", "given" : "Murielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crisponi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Ian N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fedson", "given" : "Annette C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Rosinsky", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frants", "given" : "Rune", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwilliam", "given" : "Rhian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xijing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hillman", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesaniemi", "given" : "Y Antero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskinen", "given" : "Seppo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahley", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Larrad", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukherjee", "given" : "Sutapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naitza", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00f9", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paolisso", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattaro", "given" : "Cristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Andreas F H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posthuma", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolandsson", "given" : "Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurethsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Laila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijk", "given" : "Ko Willems", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visvikis-Siest", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogelzangs", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "Kim L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jaqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnell", "given" : "John W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zethelius", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spranger", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-R\u00edos", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "105-16", "title" : "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "8\u201310", "plainTextFormattedCitation" : "8\u201310", "previouslyFormattedCitation" : "8\u201310" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }8–10 and 5 in 2-hour glucose measurements from an oral glucose tolerance test (OGTT)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.521", "ISSN" : "1546-1718", "PMID" : "20081857", "abstract" : "Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).", "author" : [ { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hivert", "given" : "Marie-France", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boesgaard", "given" : "Trine W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andreasen", "given" : "Camilla H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6ttgen", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taneera", "given" : "Jalal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bielinski", "given" : "Suzette J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Amelie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J Crawford", "given" : "Gabriel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Firmann", "given" : "Mathieu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krohn", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "L\u00e9vy-Marchal", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayor", "given" : "Vladimir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pascoe", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "142-8", "title" : "Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "11", "plainTextFormattedCitation" : "11", "previouslyFormattedCitation" : "11" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }11. A vast majority of these SNPs are associated with differences in pancreatic function through impaired insulin processing or secretion3. Cumulatively, regression models with SNPs from GWA-studies account for only <10% of variation in the traitsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajhg.2011.11.029", "ISSN" : "1537-6605", "PMID" : "22243964", "abstract" : "The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs). These studies were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders. We start by giving a number of quotes from scientists and journalists about perceived problems with GWASs. We will then briefly give the history of GWASs and focus on the discoveries made through this experimental design, what those discoveries tell us and do not tell us about the genetics and biology of complex traits, and what immediate utility has come out of these studies. Rather than giving an exhaustive review of all reported findings for all diseases and other complex traits, we focus on the results for auto-immune diseases and metabolic diseases. We return to the perceived failure or disappointment about GWASs in the concluding section.", "author" : [ { "dropping-particle" : "", "family" : "Visscher", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Matthew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Jian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1", "13" ] ] }, "language" : "English", "page" : "7-24", "publisher" : "Elsevier", "title" : "Five years of GWAS discovery.", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "12", "plainTextFormattedCitation" : "12", "previouslyFormattedCitation" : "12" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }12. However, Bayesian approaches have found polygenic models with hundreds of SNPs explain approximately 50% of heritability for type 2 diabetesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2232", "ISSN" : "1546-1718", "PMID" : "22446960", "abstract" : "The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases.", "author" : [ { "dropping-particle" : "", "family" : "Stahl", "given" : "Eli A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wegmann", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trynka", "given" : "Gosia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutierrez-Achury", "given" : "Javier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Do", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallberg", "given" : "Henrik J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurreeman", "given" : "Fina A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregersen", "given" : "Peter K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alfredsson", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siminovitch", "given" : "Katherine A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Worthington", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plenge", "given" : "Robert M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "page" : "483-9", "title" : "Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "13", "plainTextFormattedCitation" : "13", "previouslyFormattedCitation" : "13" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }13. Various propositions attempt to account for this ‘missing heritability’, including consideration of epigenetic inheritance and parent of origin effects, among othersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/456018a", "ISSN" : "1476-4687", "PMID" : "18987709", "author" : [ { "dropping-particle" : "", "family" : "Maher", "given" : "Brendan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "7218", "issued" : { "date-parts" : [ [ "2008", "11", "6" ] ] }, "page" : "18-21", "title" : "Personal genomes: The case of the missing heritability.", "type" : "article-journal", "volume" : "456" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/nature08494", "ISSN" : "1476-4687", "PMID" : "19812666", "abstract" : "Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.", "author" : [ { "dropping-particle" : "", "family" : "Manolio", "given" : "Teri A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Nancy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldstein", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hindorff", "given" : "Lucia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos", "given" : "Erin M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cardon", "given" : "Lon R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakravarti", "given" : "Aravinda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Judy H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guttmacher", "given" : "Alan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruglyak", "given" : "Leonid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mardis", "given" : "Elaine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotimi", "given" : "Charles N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slatkin", "given" : "Montgomery", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whittemore", "given" : "Alice S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clark", "given" : "Andrew G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eichler", "given" : "Evan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gibson", "given" : "Greg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haines", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mackay", "given" : "Trudy F C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visscher", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-2", "issue" : "7265", "issued" : { "date-parts" : [ [ "2009", "10", "8" ] ] }, "page" : "747-53", "title" : "Finding the missing heritability of complex diseases.", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "14,15", "plainTextFormattedCitation" : "14,15", "previouslyFormattedCitation" : "14,15" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14,15.1.1.3 Risk profile for South AsiansObservational studies and systematic reviews have emphasized the greater risk of type 2 diabetes in people of South Asian ancestry compared to white CaucasiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(00)02502-2", "ISSN" : "01406736", "PMID" : "11071182", "abstract" : "BACKGROUND: Cardiovascular disease rates vary greatly between ethnic groups in Canada. To establish whether this variation can be explained by differences in disease risk factors and subclinical atherosclerosis, we undertook a population-based study of three ethnic groups in Canada: South Asians, Chinese, and Europeans.\n\nMETHODS: 985 participants were recruited from three cities (Hamilton, Toronto, and Edmonton) by stratified random sampling. Clinical cardiovascular disease was defined by history or electrocardiographic findings. Carotid atherosclerosis was measured with B-mode ultrasonography. Conventional (smoking, hypertension, diabetes, raised cholesterol) and novel risk factors (markers of a prothrombotic state) were measured.\n\nFINDINGS: Within each ethnic group and overall, the degree of carotid atherosclerosis was associated with a higher prevalence of cardiovascular disease. South Asians had the highest prevalence of this condition compared with Europeans and Chinese (11%, 5%, and 2%, respectively, p=0.0004). Despite this finding, Europeans had more atherosclerosis (mean of the maximum intimal medial thickness 0.75 [0.16] mm) than South Asians (0.72 [0.15] mm), and Chinese (0.69 [0.16] mm). South Asians had an increased prevalence of glucose intolerance, higher total and LDL cholesterol, higher triglycerides, and lower HDL cholesterol, and much greater abnormalities in novel risk factors including higher concentrations of fibrinogen, homocysteine, lipoprotein (a), and plasminogen activator inhibitor-1.\n\nINTERPRETATION: Although there are differences in conventional and novel risk factors between ethnic groups, this variation and the degree of atherosclerosis only partly explains the higher rates of cardiovascular disease among South Asians compared with Europeans and Chinese. The increased risk of cardiovascular events could be due to factors affecting plaque rupture, the interaction between prothrombotic factors and atherosclerosis, or as yet undiscovered risk factors.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vuksan", "given" : "Vladmir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devanesen", "given" : "Sudarshan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Koon K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montague", "given" : "Patricia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelemen", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yi", "given" : "Cheelong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lonn", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hegele", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet", "id" : "ITEM-1", "issue" : "9226", "issued" : { "date-parts" : [ [ "2000", "7", "22" ] ] }, "language" : "English", "page" : "279-284", "publisher" : "Elsevier", "title" : "Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE)", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.9778/cmajo.20130064", "ISSN" : "2291-0026", "PMID" : "25295238", "abstract" : "BACKGROUND: South Asians represent about 3% of the Canadian population and have a higher burden of certain cardiovascular risk factors and cardiovascular disease (CVD) compared with white people. The objective of this study was to review the literature to compare cardiovascular risk factors and disease management practices among adult South Asian and white Canadians.\n\nMETHODS: We searched MEDLINE, Embase, Cochrane and Cumulative Index to Nursing and Allied Health Literature databases from their inception through Feb. 17, 2014 and the reference lists of the selected articles. English-language studies of interventions and observational studies of biological mechanisms underlying CVD risk in South Asians conducted in Canada were eligible for inclusion. Where appropriate, we used random-effects meta-analyses to integrate results comparing the CVD risk profiles of South Asian and white Canadians.\n\nRESULTS: We included 50 articles (n = 5\u00a0805\u00a0313 individuals) in this review. Compared with white Canadians, South Asian Canadians had a higher prevalence and incidence of CVD, an increased prevalence of diabetes (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.81 to 2.80, p\u00a0<\u00a00.001) and hypertension (OR 1.11, 95% CI 1.02 to 1.22, p\u00a0=\u00a00.02), lower high-density lipoprotein cholesterol levels (mean difference -0.19\u00a0mmol/L, 95% CI -0.25 to -0.13 mmol/L, p\u00a0<\u00a00.001) and a higher percentage of body fat (men: absolute mean difference 3.23%, 95% CI 0.83% to 5.62%, p\u00a0=\u00a00.008; women: absolute mean difference 4.09%, 95% CI 3.46% to 4.72%, p\u00a0<\u00a00.001). South Asian people are also more sedentary, consume higher levels of carbohydrates and are less likely to smoke tobacco (OR 0.38, 95% CI 0.24 to 0.60, p\u00a0<\u00a00.001]) than white Canadians. No differences in access to diagnostic tests, outcomes following cardiovascular surgery or use of cardiac rehabilitation programs were apparent.\n\nINTERPRETATION: Compared with white people, South Asian people living in Canada have a higher prevalence and incidence of CVD and possess a unique cardiovascular risk profile.", "author" : [ { "dropping-particle" : "", "family" : "Rana", "given" : "Ayesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Russell J", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kandasamy", "given" : "Sujane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lear", "given" : "Scott A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CMAJ open", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "7" ] ] }, "page" : "E183-91", "title" : "Cardiovascular risk among South Asians living in Canada: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.cjca.2014.10.005", "ISSN" : "0828-282X", "author" : [ { "dropping-particle" : "", "family" : "Valera", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sohani", "given" : "Z.N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rana", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poirier", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "S.S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian Journal of Cardiology", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "language" : "English", "publisher" : "Elsevier", "title" : "The ethno-epidemiology of obesity", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "16\u201318", "plainTextFormattedCitation" : "16\u201318", "previouslyFormattedCitation" : "16\u201318" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16–18. White Caucasians are broadly defined as those individuals from the European continentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2119/molmed.2009.00094", "ISSN" : "1528-3658", "PMID" : "19707526", "abstract" : "The definition of European population genetic substructure and its application to understanding complex phenotypes is becoming increasingly important. In the current study using over 4,000 subjects genotyped for 300,000 single-nucleotide polymorphisms (SNPs), we provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs) for application in genetic studies. In general, the graphical description of these principal components analyses (PCA) of diverse European subjects showed a strong correspondence to the geographical relationships of specific countries or regions of origin. Clearer separation of different ethnic and regional populations was observed when northern and southern European groups were considered separately and the PCA results were influenced by the inclusion or exclusion of different self-identified population groups including Ashkenazi Jewish, Sardinian, and Orcadian ethnic groups. SNP AIM sets were identified that could distinguish the regional and ethnic population groups. Moreover, the studies demonstrated that most allele frequency differences between different European groups could be controlled effectively in analyses using these AIM sets. The European substructure AIMs should be widely applicable to ongoing studies to confirm and delineate specific disease susceptibility candidate regions without the necessity of performing additional genome-wide SNP studies in additional subject sets.", "author" : [ { "dropping-particle" : "", "family" : "Tian", "given" : "Chao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kosoy", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nassir", "given" : "Rami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Villoslada", "given" : "Pablo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klareskog", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammarstr\u00f6m", "given" : "Lennart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garchon", "given" : "Henri-Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pulver", "given" : "Ann E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ransom", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregersen", "given" : "Peter K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seldin", "given" : "Michael F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular medicine (Cambridge, Mass.)", "id" : "ITEM-1", "issue" : "11-12", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "371-83", "title" : "European population genetic substructure: further definition of ancestry informative markers for distinguishing among diverse European ethnic groups.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "19", "plainTextFormattedCitation" : "19", "previouslyFormattedCitation" : "19" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19. Similarly, South Asians are people originating from the Indian subcontinent, falling largely within two linguistic groups – Indo-Aryan and DravidianADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nature08365", "ISSN" : "1476-4687", "PMID" : "19779445", "abstract" : "India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' (ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.", "author" : [ { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "7263", "issued" : { "date-parts" : [ [ "2009", "9", "24" ] ] }, "page" : "489-94", "title" : "Reconstructing Indian population history.", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ajhg.2013.07.006", "ISSN" : "1537-6605", "PMID" : "23932107", "abstract" : "Most Indian groups descend from a mixture of two genetically divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians (ASI) not closely related to groups outside the subcontinent. The date of mixture is unknown but has implications for understanding Indian history. We report genome-wide data from 73 groups from the Indian subcontinent and analyze linkage disequilibrium to estimate ANI-ASI mixture dates ranging from about 1,900 to 4,200 years ago. In a subset of groups, 100% of the mixture is consistent with having occurred during this period. These results show that India experienced a demographic transformation several thousand years ago, from a region in which major population mixture was common to one in which mixture even between closely related groups became rare because of a shift to endogamy.", "author" : [ { "dropping-particle" : "", "family" : "Moorjani", "given" : "Priya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lipson", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Po-Ru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Govindaraj", "given" : "Periyasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Bonnie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "9", "5" ] ] }, "page" : "422-38", "title" : "Genetic evidence for recent population mixture in India.", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "20,21", "plainTextFormattedCitation" : "20,21", "previouslyFormattedCitation" : "20,21" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20,21. This includes individuals who originate from India, Pakistan, Sri Lanka, Bangladesh, Bhutan, Nepal, and Maldives. Estimates of type 2 diabetes demonstrate a 2-5 fold higher risk in this group compared to white CaucasiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-006-0325-1", "ISSN" : "0012-186X", "PMID" : "16847701", "abstract" : "A popular hypothesis for the greater prevalence of type 2 diabetes and cardiovascular disease in UK south Asians is that they have an increased susceptibility of developing insulin resistance in response to certain environmental factors, including obesity and adoption of a sedentary lifestyle. Insulin resistance is postulated as a central feature of the metabolic syndrome, culminating in type 2 diabetes, atherosclerotic vascular disease and CHD; a pathway potentially accelerated by migration/urbanisation. We describe and compare the prevalence of type 2 diabetes, cardiovascular disease and their associated risk factors in UK south Asian and white Caucasian populations to determine possible reasons for the increased preponderance of these diseases in south Asians, and highlight key evidence for optimal risk factor management. Finally, we describe a UK community-based programme that attempts to reduce the morbidity and mortality from type 2 diabetes and cardiovascular disease in south Asians through a new approach to management.", "author" : [ { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dixon", "given" : "A N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellary", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanif", "given" : "M W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raymond", "given" : "N T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2006", "10" ] ] }, "page" : "2234-46", "title" : "Type 2 diabetes and cardiovascular risk in the UK south Asian community.", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.9778/cmajo.20130064", "ISSN" : "2291-0026", "PMID" : "25295238", "abstract" : "BACKGROUND: South Asians represent about 3% of the Canadian population and have a higher burden of certain cardiovascular risk factors and cardiovascular disease (CVD) compared with white people. The objective of this study was to review the literature to compare cardiovascular risk factors and disease management practices among adult South Asian and white Canadians.\n\nMETHODS: We searched MEDLINE, Embase, Cochrane and Cumulative Index to Nursing and Allied Health Literature databases from their inception through Feb. 17, 2014 and the reference lists of the selected articles. English-language studies of interventions and observational studies of biological mechanisms underlying CVD risk in South Asians conducted in Canada were eligible for inclusion. Where appropriate, we used random-effects meta-analyses to integrate results comparing the CVD risk profiles of South Asian and white Canadians.\n\nRESULTS: We included 50 articles (n = 5\u00a0805\u00a0313 individuals) in this review. Compared with white Canadians, South Asian Canadians had a higher prevalence and incidence of CVD, an increased prevalence of diabetes (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.81 to 2.80, p\u00a0<\u00a00.001) and hypertension (OR 1.11, 95% CI 1.02 to 1.22, p\u00a0=\u00a00.02), lower high-density lipoprotein cholesterol levels (mean difference -0.19\u00a0mmol/L, 95% CI -0.25 to -0.13 mmol/L, p\u00a0<\u00a00.001) and a higher percentage of body fat (men: absolute mean difference 3.23%, 95% CI 0.83% to 5.62%, p\u00a0=\u00a00.008; women: absolute mean difference 4.09%, 95% CI 3.46% to 4.72%, p\u00a0<\u00a00.001). South Asian people are also more sedentary, consume higher levels of carbohydrates and are less likely to smoke tobacco (OR 0.38, 95% CI 0.24 to 0.60, p\u00a0<\u00a00.001]) than white Canadians. No differences in access to diagnostic tests, outcomes following cardiovascular surgery or use of cardiac rehabilitation programs were apparent.\n\nINTERPRETATION: Compared with white people, South Asian people living in Canada have a higher prevalence and incidence of CVD and possess a unique cardiovascular risk profile.", "author" : [ { "dropping-particle" : "", "family" : "Rana", "given" : "Ayesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Russell J", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kandasamy", "given" : "Sujane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lear", "given" : "Scott A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CMAJ open", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "7" ] ] }, "page" : "E183-91", "title" : "Cardiovascular risk among South Asians living in Canada: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "17,22", "plainTextFormattedCitation" : "17,22", "previouslyFormattedCitation" : "22,17" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }17,22. Furthermore, once diagnosed with diabetes, South Asians have a greater predisposition to cardiovascular diseaseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/hc4601.099487", "ISSN" : "0009-7322", "abstract" : "This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiologic transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.", "author" : [ { "dropping-particle" : "", "family" : "Yusuf", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ounpuu", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2001", "11", "27" ] ] }, "page" : "2746-2753", "title" : "Global Burden of Cardiovascular Diseases: Part I: General Considerations, the Epidemiologic Transition, Risk Factors, and Impact of Urbanization", "type" : "article-journal", "volume" : "104" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1161/hc4701.099488", "ISSN" : "0009-7322", "abstract" : "This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiological transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.", "author" : [ { "dropping-particle" : "", "family" : "Yusuf", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ounpuu", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation", "id" : "ITEM-2", "issue" : "23", "issued" : { "date-parts" : [ [ "2001", "12", "4" ] ] }, "page" : "2855-2864", "title" : "Global Burden of Cardiovascular Diseases: Part II: Variations in Cardiovascular Disease by Specific Ethnic Groups and Geographic Regions and Prevention Strategies", "type" : "article-journal", "volume" : "104" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/S0140-6736(00)02502-2", "ISSN" : "01406736", "PMID" : "11071182", "abstract" : "BACKGROUND: Cardiovascular disease rates vary greatly between ethnic groups in Canada. To establish whether this variation can be explained by differences in disease risk factors and subclinical atherosclerosis, we undertook a population-based study of three ethnic groups in Canada: South Asians, Chinese, and Europeans.\n\nMETHODS: 985 participants were recruited from three cities (Hamilton, Toronto, and Edmonton) by stratified random sampling. Clinical cardiovascular disease was defined by history or electrocardiographic findings. Carotid atherosclerosis was measured with B-mode ultrasonography. Conventional (smoking, hypertension, diabetes, raised cholesterol) and novel risk factors (markers of a prothrombotic state) were measured.\n\nFINDINGS: Within each ethnic group and overall, the degree of carotid atherosclerosis was associated with a higher prevalence of cardiovascular disease. South Asians had the highest prevalence of this condition compared with Europeans and Chinese (11%, 5%, and 2%, respectively, p=0.0004). Despite this finding, Europeans had more atherosclerosis (mean of the maximum intimal medial thickness 0.75 [0.16] mm) than South Asians (0.72 [0.15] mm), and Chinese (0.69 [0.16] mm). South Asians had an increased prevalence of glucose intolerance, higher total and LDL cholesterol, higher triglycerides, and lower HDL cholesterol, and much greater abnormalities in novel risk factors including higher concentrations of fibrinogen, homocysteine, lipoprotein (a), and plasminogen activator inhibitor-1.\n\nINTERPRETATION: Although there are differences in conventional and novel risk factors between ethnic groups, this variation and the degree of atherosclerosis only partly explains the higher rates of cardiovascular disease among South Asians compared with Europeans and Chinese. The increased risk of cardiovascular events could be due to factors affecting plaque rupture, the interaction between prothrombotic factors and atherosclerosis, or as yet undiscovered risk factors.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vuksan", "given" : "Vladmir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devanesen", "given" : "Sudarshan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Koon K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montague", "given" : "Patricia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelemen", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yi", "given" : "Cheelong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lonn", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hegele", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet", "id" : "ITEM-3", "issue" : "9226", "issued" : { "date-parts" : [ [ "2000", "7", "22" ] ] }, "language" : "English", "page" : "279-284", "publisher" : "Elsevier", "title" : "Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE)", "type" : "article-journal", "volume" : "356" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "16,23,24", "plainTextFormattedCitation" : "16,23,24", "previouslyFormattedCitation" : "23,24,16" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }16,23,24 compared to Caucasians. A comparison between South Asians and whites over a follow-up period of 11 years found that the former were twice as likely to die from heart and circulatory disease in those aged 30–64 years at baseline. Lastly, among South Asians in the surviving cohort, there was a 3.8 times greater likelihood of myocardial infarction than white CaucasiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/(SICI)1096-9136(199801)15:1<53::AID-DIA521>3.0.CO;2-V", "ISSN" : "0742-3071", "PMID" : "9472864", "abstract" : "Over 20% of middle aged and elderly South Asian people throughout the world have diabetes. The associated mortality and morbidity risks are unclear. We compared mortality and morbidity in a cohort of South Asian and European people with diabetes in London, UK, in an 11-year follow-up of a population-based sample of 730 South Asians (mean age 55 in 1984) and 304 Europeans (mean age 67 in 1984) with diabetes aged 30 years and above in 1984. By 1995, 242 (33%) of South Asians, and 172 (57%) of Europeans had died. The all-cause mortality rate ratio (South Asian versus European) was 1.50 (95% CI 0.72-3.12) for those aged 30-54 years at baseline. Ethnic differences in mortality rates were abolished or reversed in people aged 65 years and above at baseline. The mortality rate ratio for circulatory deaths was 1.80 (95% CI 1.03-3.16, p < 0.05) and for heart disease was 2.02 (95% CI 1.04-3.92, p < 0.05) in those aged 30-64 years at baseline. Seventy-seven per cent of South Asian deaths were caused by circulatory disease, compared with 46% of European deaths. South Asian survivors were 3.8 times (95% CI 1.8-8.0, p = 0.001) more likely to report a history of myocardial infarction than Europeans. South Asian adults with diabetes show a markedly increased predisposition to cardiovascular disease compared with Europeans, especially in younger people. This emphasizes the urgent need to reduce cardiovascular risk in this vulnerable group.", "author" : [ { "dropping-particle" : "", "family" : "Mather", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fuller", "given" : "J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1998", "1" ] ] }, "page" : "53-9", "title" : "Mortality and morbidity from diabetes in South Asians and Europeans: 11-year follow-up of the Southall Diabetes Survey, London, UK.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "25", "plainTextFormattedCitation" : "25", "previouslyFormattedCitation" : "25" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }25. Various metabolic abnormalities likely lead to this increased risk; a cross-sectional study of 1,711 South Asians and 2,346 Caucasians found a higher prevalence of dyslipidemia, impaired glucose homeostasis, proportion of diagnosed diabetes, and central obesity in South Asians. The age-standardized prevalence of metabolic syndrome was 46.3% in South Asian men and 30.8% in women compared to only 18.8% in white Caucasian men and 9.1% in womenADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-005-1689-3", "ISSN" : "0012-186X", "PMID" : "15759110", "abstract" : "AIMS/HYPOTHESIS: The aim of this study was to study differences in the prevalence of the metabolic syndrome and its associations with prevalent CHD according to ethnicity and sex.\n\nMETHODS: We performed a combined analysis of two population-based cross-sectional studies conducted between 1988 and 1991 that followed identical protocols. Participants (aged 40-69 years) comprised 2,346 Europeans (76% male), 1,711 South Asians (83% male) and 803 African-Caribbeans (57% male) resident in west London. Fasting blood, overnight urine collection, clinical and anthropometric measurements were performed. Clinical history or major ECG changes defined prevalent CHD. The metabolic syndrome was defined according to the criteria recommended by the World Health Organization (WHO) and the National Cholesterol Education Programme (NCEP).\n\nRESULTS: The prevalence of the metabolic syndrome was highest in South Asians (WHO, men 46%, women 31%; NCEP, men 29%, women 32%) and lowest in European women (WHO, 9%; NCEP, 14%). The prevalence of CHD was 10% in South Asian men, 9% in European men, 5-6% in African-Caribbeans and European women, and 2% in South Asian women. The metabolic syndrome was associated with prevalent CHD in European men [NCEP, odds ratio (OR)=1.6, 95% CI 1.2-2.4; WHO, OR=1.7, 95% CI 1.2-2.5] and South Asian men (NCEP, OR=2.1, 95% CI 1.5-3.1; WHO, OR=1.6, 95% CI 1.1-2.3). Associations with CHD were weaker in African-Caribbeans and were inconsistent among European women.\n\nCONCLUSIONS/INTERPRETATION: The current definitions of the metabolic syndrome give an inconsistent picture of cardiovascular disease risk when applied to different ethnic groups within the UK. Prospective studies are needed to validate workable ethnic-specific definitions.", "author" : [ { "dropping-particle" : "", "family" : "Tillin", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeigue", "given" : "P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godsland", "given" : "I F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2005", "4" ] ] }, "page" : "649-56", "title" : "Metabolic syndrome and coronary heart disease in South Asians, African-Caribbeans and white Europeans: a UK population-based cross-sectional study.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "26", "plainTextFormattedCitation" : "26", "previouslyFormattedCitation" : "26" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }26. Studies from urban India report similar age-standardized prevalence of metabolic syndrome. Prasad et al found an overall prevalence of 33.5% (24.9 % in males and 42.3% in females)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4103/0975-3583.98895", "ISSN" : "0976-2833", "PMID" : "22923938", "abstract" : "OBJECTIVES: To determine the prevalence of metabolic syndrome and to identify predictors for the same, specific to an underdeveloped urban locale of Eastern India.\n\nMATERIALS AND METHODS: \n\nSTUDY DESIGN: Population-based cross-sectional study, with multistage random sampling technique.\n\nSETTING: Urban city-dwellers in Orissa one of the poorest states of Eastern India bordering a prosperous state of Andhra Pradesh of Southern India.\n\nPARTICIPANTS: 1178 adults of age 20-80 years randomly selected from 37 electoral wards of the urban city. Definition of Metabolic Syndrome: We followed a unified definition of the metabolic syndrome by joint interim statement of five major scientific organizations - the International Diabetes Federation, the National Heart, Lung, and Blood Institute, the American Heart Association, the World Heart Federation, the International Atherosclerosis Society, and the International Association of the Study of Obesity. Individuals who meet at least three of five clinical criteria of abdominal obesity, hypertriglyceredimia, low HDL, hypertension, and hyperglycemia are diagnosed as having the condition; presence of none of these criteria is mandatory. Explicit cut points are defined for all criteria, except elevated waist circumference, which must rely on population and country-specific definitions.\n\nMAIN OUTCOME MEASURE: Prevalence and significant predictors of metabolic syndrome.\n\nSTATISTICAL ANALYSIS: Both descriptive and multivariable logistic regression analyses.\n\nRESULTS: Age-standardized prevalence rates of metabolic syndrome were 33.5% overall, 24.9 % in males and 42.3% in females. Older age, female gender, general obesity, inadequate fruit intake, hypercholesterolemia, and middle-to-high socioeconomic status significantly contributed to increased risk of metabolic syndrome.\n\nCONCLUSION: Metabolic syndrome is a significant public health problem even in one of the poorest states of India that needs to be tackled with proven strategies.", "author" : [ { "dropping-particle" : "", "family" : "Prasad", "given" : "D S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kabir", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dash", "given" : "A K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "B C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of cardiovascular disease research", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "7" ] ] }, "page" : "204-11", "title" : "Prevalence and risk factors for metabolic syndrome in Asian Indians: A community study from urban Eastern India.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "27", "plainTextFormattedCitation" : "27", "previouslyFormattedCitation" : "27" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }27, though there is some variation between urban and rural regionsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1046/j.1464-5491.2001.00421.x", "ISSN" : "0742-3071", "author" : [ { "dropping-particle" : "", "family" : "Mohan", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shanthirani", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deepa", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Premalatha", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sastry", "given" : "N. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saroja", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic Medicine", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2001", "4" ] ] }, "page" : "280-287", "title" : "Intra-urban differences in the prevalence of the metabolic syndrome in southern India - the Chennai Urban Population Study (CUPS No. 4)", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/dmrr.658", "ISSN" : "1520-7552", "PMID" : "16752431", "abstract" : "AIM: To compare the prevalence of metabolic syndrome (MS) using the World Health Organisation (WHO), Adult Treatment Panel III (ATPIII) and International Diabetes Federation (IDF) criteria of MS in an urban south Indian population, and their ability to identify coronary artery disease (CAD) in males and females.\n\nMETHODS: Chennai Urban Rural Epidemiology Study (CURES) is one of the largest epidemiological studies on diabetes carried out in India, in which 26 001 individuals aged >or=20 years were screened using systematic random sampling method. Every tenth subject recruited in Phase 1 of CURES was requested to participate in Phase 3, and the response rate was 90.4%. An oral glucose tolerance test (OGTT) was performed in all individuals except self-reported diabetic subjects. Anthropometric measurements and lipid estimations were done in all subjects and the prevalence of MS estimated using the three criteria. Diagnosis of CAD, made by resting 12 lead ECG, was compared by the three criteria of MS.\n\nRESULTS: MS was identified in 546 subjects (23.2%) by WHO criteria, 430 subjects (18.3%) by ATPIII criteria and 607 subjects (25.8%) by IDF criteria. Only 224 of these subjects were identified by all the three criteria. There was an increased risk of probable CAD in MS subjects diagnosed by WHO criteria (odds ratio (OR) 3.86, 95% Confidence Interval (CI), 2.37-6.29, p < 0.001), compared to ATPIII criteria (OR 2.19, 95% CI 1.30-3.67, p < 0.05) and IDF criteria (OR 1.90, 95% CI 1.16-3.12, p < 0.05). The WHO criteria marked out a much higher population for CAD risk compared to ATPIII and IDF criteria in males, but not in females.\n\nCONCLUSION: In Asian Indians, the WHO, ATPIII and IDF criteria of MS identify different individuals. The WHO criteria identify a greater number of CAD subjects in males, but not in females.", "author" : [ { "dropping-particle" : "", "family" : "Deepa", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooq", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Datta", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deepa", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes/metabolism research and reviews", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "2" ] ] }, "page" : "127-34", "title" : "Prevalence of metabolic syndrome using WHO, ATPIII and IDF definitions in Asian Indians: the Chennai Urban Rural Epidemiology Study (CURES-34).", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "28,29", "plainTextFormattedCitation" : "28,29", "previouslyFormattedCitation" : "28,29" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }28,29.Detailed assessments in South Asians reveal that they possess a greater propensity for insulin resistance and beta-cell dysfunction. A comparison of South Asians and white Caucasians matched on lifestyle factors and body-mass index (BMI) found that while South Asians demonstrated a 30% increase in basal beta-cell responsiveness, this increased function was not sufficient to compensate for a greater degree of insulin resistance, as evidenced by a 60% reduction in disposition index, a measure of beta-cell response to insulin resistanceADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1073/pnas.0608537103", "ISSN" : "0027-8424", "PMID" : "17114290", "abstract" : "Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM and that insulin resistance is strongly associated with increases in hepatic (HTG) and/or intramyocellular lipid content, little is known about the prevalence of insulin resistance and potential differences in intracellular lipid distribution among healthy, young, lean individuals of different ethnic groups. To examine this question, 482 young, lean, healthy, sedentary, nonsmoking Eastern Asians (n = 49), Asian-Indians (n = 59), Blacks (n = 48), Caucasians (n = 292), and Hispanics (n = 34) underwent an oral glucose tolerance test to assess whole-body insulin sensitivity by an insulin sensitivity index. In addition, intramyocellular lipid and HTG contents were measured by using proton magnetic resonance spectroscopy. The prevalence of insulin resistance, defined as the lower quartile of insulin sensitivity index, was approximately 2- to 3-fold higher in the Asian-Indians compared with all other ethnic groups, and this could entirely be attributed to a 3- to 4-fold increased prevalence of insulin resistance in Asian-Indian men. This increased prevalence of insulin resistance in the Asian-Indian men was associated with an approximately 2-fold increase in HTG content and plasma IL-6 concentrations compared with Caucasian men. These data demonstrate important ethnic and gender differences in the pathogenesis of insulin resistance in Asian-Indian men and have important therapeutic implications for treatment of T2DM and for the development of steatosis-related liver disease in this ethnic group.", "author" : [ { "dropping-particle" : "", "family" : "Petersen", "given" : "Kitt Falk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dufour", "given" : "Sylvie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feng", "given" : "Jing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Befroy", "given" : "Douglas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dziura", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dalla Man", "given" : "Chiara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cobelli", "given" : "Claudio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shulman", "given" : "Gerald I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the National Academy of Sciences of the United States of America", "id" : "ITEM-1", "issue" : "48", "issued" : { "date-parts" : [ [ "2006", "11", "28" ] ] }, "page" : "18273-7", "title" : "Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men.", "type" : "article-journal", "volume" : "103" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "30", "plainTextFormattedCitation" : "30", "previouslyFormattedCitation" : "30" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }30. Similarly, using a 2-hour oral glucose challenge and 2-hour euglycemic hyperinsulinemic clamps, Raji et al show that South Asians exhibit fasting hyperinsulinemia, higher glucose and insulin levels during an OGTT, and reduced glucose disposal rate, despite having similar fasting glucose measurementsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jcem.86.11.7992", "ISSN" : "0021-972X", "PMID" : "11701707", "abstract" : "Previous studies have shown that Asian Indians (AIs) are insulin resistant and at high risk for developing diabetes and coronary heart disease, compared with Caucasians. To examine whether differences in body fat distribution contribute to this risk, 12 healthy AIs and 12 Caucasians matched for age and body mass index (BMI) underwent a 75-g oral glucose tolerance test, 2-h euglycemic hyperinsulinemic clamp, abdominal (L2-3) computed tomography scan, and fasting lipid and plasminogen activator inhibitor-1 (PAI-1) levels. Despite similar fasting plasma glucose levels, AIs exhibited fasting hyperinsulinemia (P = 0.001), higher glucose (P = 0.03) and insulin (P = 0.004) levels during the oral glucose tolerance test, and reduced glucose disposal rate (R(d)) (4.7 +/- 0.4 vs. 7.5 +/- 0.3 mg/kg per min, P < 0.0001) during the clamp. AIs had significantly lower high-density lipoprotein, higher low-density lipoprotein, and significantly higher PAI-1 levels (P = 0.01). Despite similar BMI, AIs had significantly greater total abdominal fat (P = 0.04) and visceral fat (P = 0.04). In all subjects, measures of fat mass were inversely correlated with R(d) during the clamp (r = -0.47 to -0.61, P < 0.01-0.001). Visceral fat mass was correlated with triglycerides, low-density lipoprotein, and high-density lipoprotein (P < 0.002-0.0001). PAI-1 was inversely correlated with R(d) in AIs (r = -0.70, P < 0.01) and not in Caucasians (r = -0.24, P = 0.44). For comparable BMI and age, healthy AIs have physiologic markers for insulin resistance, dyslipidemia, and increased cardiovascular risk, compared with Caucasians. Alterations in body fat distribution--particularly increased visceral fat--may contribute to these abnormalities.", "author" : [ { "dropping-particle" : "", "family" : "Raji", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seely", "given" : "E W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arky", "given" : "R A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simonson", "given" : "D C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2001", "11" ] ] }, "page" : "5366-71", "title" : "Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "31", "plainTextFormattedCitation" : "31", "previouslyFormattedCitation" : "31" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31. Lastly, a 5-year prospective comparison of fasting glucose, 2-hour post load glucose, fasting insulin, 2-hour post load insulin, homeostatic model assessment of insulin sensitivity (HOMA-%S), and insulin secretion (HOMA-%B) suggest that in addition to lowered sensitivity to the effects of insulin, South Asians also possess reduced beta-cell function. This is demonstrated by steeper age-related trajectories of fasting glucose, higher post-load glucose, fasting insulin, post-load insulin and HOMA-%B, as well as lower HOMA-%S among South Asians compared to whitesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-014-3448-9", "ISSN" : "1432-0428", "PMID" : "25431266", "abstract" : "AIMS/HYPOTHESIS: South Asian individuals have an increased prevalence of type 2 diabetes, but little is known about the development of glycaemic traits in this ethnic group. We compared age-related changes in glycaemic traits between non-diabetic South Asian and white participants.\n\nMETHODS: In a prospective British occupational cohort with 5-yearly clinical examinations (n\u2009=\u2009230/5,749 South Asian/white participants, age 39-79\u00a0years at baseline), age-related trajectories of fasting glucose (FG) and 2\u00a0h post-load glucose (PLG), log-transformed fasting insulin (FINS) and 2\u00a0h post-load insulin (PLINS), HOMA insulin sensitivity (HOMA2-%S) and HOMA insulin secretion (HOMA2-%B) were fitted for South Asian and white individuals who remained free of diabetes between 1991 and 2009.\n\nRESULTS: In sex-adjusted multilevel models, FG was stable in white participants but increased with age in South Asians (0.12 [SE\u2009=\u20090.04] mmol/l per decade). PLG, FINS and PLINS levels were lower among white participants (by 0.271 [SE\u2009=\u20090.092] mmol/l, 0.306 [SE\u2009=\u20090.046] log pmol/l, 0.707 [SE\u2009=\u20090.059] log pmol/l at age 50, respectively) compared with South Asians, although their age-related trajectories were parallel. HOMA2-%S was higher (0.226 [SE\u2009=\u20090.038] at age 50) and HOMA2-%B lower (by 0.189 [SE\u2009=\u20090.026] at age 50) among white than South Asian participants. The age-related decline in HOMA2-%S was similar in these groups, but the age-related increase in HOMA2-%B was greater in white participants (0.04 [SE\u2009=\u20090.02] per decade). This difference was explained by obesity, lifestyle and social status.\n\nCONCLUSIONS/INTERPRETATION: Findings from a diabetes-free population suggest an inadequate pancreatic beta cell reserve in South Asians, as a significantly steeper age-related increase in FG was observed in this ethnic group compared with white individuals.", "author" : [ { "dropping-particle" : "", "family" : "Ikehara", "given" : "Satoyo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tab\u00e1k", "given" : "Adam G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akbaraly", "given" : "Tasnime N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hulm\u00e1n", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivim\u00e4ki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iso", "given" : "Hiroyasu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "page" : "534-42", "title" : "Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study.", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "32", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "32" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32. Anthropometric characteristics also differ in this group. The superficial subcutaneous adipose tissue (SSAT) compartment is the site of primary adipose tissue storage in the body and constitutes the vast majority of adipose tissue in the lower limbs. With increasing levels of adiposity, these stores are used up and fat is stored in the deep subcutaneous (DSAT) and the visceral adipose tissue (VAT) compartments. Whereas the SSAT is relatively metabolically inert, the DSAT and VAT are implicated in transmembrane fatty acid flux and associated with dyslipidemia and dysglycemiaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ije/dyl245", "ISSN" : "0300-5771", "PMID" : "17510078", "abstract" : "The rates of coronary disease have accelerated dramatically amongst South Asians, driven to an important extent by the atherogenic dyslipidemia and type 2 diabetes that have become so common amongst them. These precursors of vascular disease appear at lower absolute amounts of adipose tissue in South Asians than in whites. In this paper, we set out a new hypothesis--the adipose tissue overflow hypothesis--to account for these findings. The adipose tissue mass within our bodies can be divided into three different compartments: superficial subcutaneous adipose tissue, deep subcutaneous adipose tissue and visceral adipose tissue. The superficial subcutaneous adipose tissue compartment is the primary compartment, is present throughout the body, and constitutes the vast majority of the adipose tissue in the lower limb. With energy excess, the secondary adipose tissue compartments--the deep subcutaneous (mainly upper body) and the visceral adipose tissue compartments--become more prominent. Superficial subcutaneous adipose tissue is relatively inert metabolically, whereas the other two compartments are characterized by higher transmembrane fatty acid flux rates and thus are more closely linked to dyslipidemia and dysglycemia. We hypothesize that the superficial subcutaneous adipose tissue compartment is larger in whites than in South Asians. If so, as obesity develops, South Asians exhaust the storage capacity of their superficial subcutaneous adipose tissue compartment before whites do and that is why they develop the metabolic complications of upper body obesity at lower absolute masses of adipose tissue than white people.", "author" : [ { "dropping-particle" : "", "family" : "Sniderman", "given" : "Allan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhopal", "given" : "Raj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarrafzadegan", "given" : "Nizal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tchernof", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "2", "1" ] ] }, "page" : "220-5", "title" : "Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "33", "plainTextFormattedCitation" : "33", "previouslyFormattedCitation" : "33" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }33. Comparisons of these regions report that South Asians have greater total abdominal and visceral fatADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jcem.86.11.7992", "ISSN" : "0021-972X", "PMID" : "11701707", "abstract" : "Previous studies have shown that Asian Indians (AIs) are insulin resistant and at high risk for developing diabetes and coronary heart disease, compared with Caucasians. To examine whether differences in body fat distribution contribute to this risk, 12 healthy AIs and 12 Caucasians matched for age and body mass index (BMI) underwent a 75-g oral glucose tolerance test, 2-h euglycemic hyperinsulinemic clamp, abdominal (L2-3) computed tomography scan, and fasting lipid and plasminogen activator inhibitor-1 (PAI-1) levels. Despite similar fasting plasma glucose levels, AIs exhibited fasting hyperinsulinemia (P = 0.001), higher glucose (P = 0.03) and insulin (P = 0.004) levels during the oral glucose tolerance test, and reduced glucose disposal rate (R(d)) (4.7 +/- 0.4 vs. 7.5 +/- 0.3 mg/kg per min, P < 0.0001) during the clamp. AIs had significantly lower high-density lipoprotein, higher low-density lipoprotein, and significantly higher PAI-1 levels (P = 0.01). Despite similar BMI, AIs had significantly greater total abdominal fat (P = 0.04) and visceral fat (P = 0.04). In all subjects, measures of fat mass were inversely correlated with R(d) during the clamp (r = -0.47 to -0.61, P < 0.01-0.001). Visceral fat mass was correlated with triglycerides, low-density lipoprotein, and high-density lipoprotein (P < 0.002-0.0001). PAI-1 was inversely correlated with R(d) in AIs (r = -0.70, P < 0.01) and not in Caucasians (r = -0.24, P = 0.44). For comparable BMI and age, healthy AIs have physiologic markers for insulin resistance, dyslipidemia, and increased cardiovascular risk, compared with Caucasians. Alterations in body fat distribution--particularly increased visceral fat--may contribute to these abnormalities.", "author" : [ { "dropping-particle" : "", "family" : "Raji", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seely", "given" : "E W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arky", "given" : "R A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simonson", "given" : "D C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2001", "11" ] ] }, "page" : "5366-71", "title" : "Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1749-6632.2012.06838.x", "ISSN" : "1749-6632", "PMID" : "23317344", "abstract" : "Type 2 diabetes mellitus (T2DM) is one of the leading causes of morbidity and mortality. While all ethnic groups are affected, the prevalence of T2DM in South Asians, both in their home countries and abroad, is extremely high and is continuing to rise rapidly. Innate biological susceptibilities coupled with rapid changes in physical activity, diet, and other lifestyle behaviors are contributing factors propelling the increased burden of disease in this population. The large scope of this problem calls for investigations into the cause of increased susceptibility and preventative efforts at both the individual and population level that are aggressive, culturally sensitive, and start early. In this review, we outline the biological and environmental factors that place South Asians at elevated risk for T2DM, compared with Caucasian and other ethnic groups.", "author" : [ { "dropping-particle" : "", "family" : "Gujral", "given" : "Unjali P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pradeepa", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weber", "given" : "Mary Beth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narayan", "given" : "K M Venkat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the New York Academy of Sciences", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "4" ] ] }, "page" : "51-63", "title" : "Type 2 diabetes in South Asians: similarities and differences with white Caucasian and other populations.", "type" : "article-journal", "volume" : "1281" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "31,34", "plainTextFormattedCitation" : "31,34", "previouslyFormattedCitation" : "31,34" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,34, lower fat-free massADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)15269-5", "ISSN" : "1474-547X", "PMID" : "14726172", "author" : [ { "dropping-particle" : "", "family" : "Yajnik", "given" : "Chittaranjan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yudkin", "given" : "John S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9403", "issued" : { "date-parts" : [ [ "2004", "1", "10" ] ] }, "language" : "English", "page" : "163", "publisher" : "Elsevier", "title" : "The Y-Y paradox.", "type" : "article-journal", "volume" : "363" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "10.1210/jcem.84.1.5371", "abstract" : "There is a high prevalence of type 2 diabetes mellitus and coronary artery disease among urban and migrant Asian Indians despite the absence of traditional risk factors. Evidence exists that Asian Indians are more hyperinsulinemic than Caucasians and that hyperinsulinemia may be important in the development of these diseases. To test whether insulin action was related to total or regional adiposity and to explore the potential role of plasma leptin and lipids, we measured insulin-mediated glucose disposal by the euglycemic insulin clamp, adipose distribution and muscle volume using computed axial tomography, and fasting serum leptin and lipid levels in 20 healthy Asian Indian male volunteers (age, 36 \u00b1 10 yr). A mean body mass index of 24.5 \u00b1 2.5 kg/m2 was associated with an unusually high percentage of body fat (33 \u00b1 7%). The majority of the fat was sc, and 16% was visceral (intraabdominal) adipose tissue. The majority (66%) of these nonobese men were insulin resistant. The mean fasting serum leptin leve...", "author" : [ { "dropping-particle" : "", "family" : "Banerji", "given" : "Mary Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faridi", "given" : "Nuzhat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atluri", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaiken", "given" : "Rochelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lebovitz", "given" : "Harold E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Clinical Endocrinology & Metabolism", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "7", "1" ] ] }, "language" : "en", "publisher" : "Endocrine Society", "title" : "Body Composition, Visceral Fat, Leptin, and Insulin Resistance in Asian Indian Men1", "type" : "article" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0000812", "ISSN" : "1932-6203", "author" : [ { "dropping-particle" : "", "family" : "Chandalia", "given" : "Manisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seenivasan", "given" : "Thanalakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Livingston", "given" : "Edward H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Snell", "given" : "Peter G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abate", "given" : "Nicola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Maedler", "given" : "Kathrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8", "29" ] ] }, "page" : "e812", "title" : "Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1046/j.1467-789X.2002.00065.x", "ISSN" : "1467-7881", "author" : [ { "dropping-particle" : "", "family" : "Deurenberg", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deurenberg-Yap", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guricci", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity Reviews", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2002", "8" ] ] }, "page" : "141-146", "title" : "Asians are different from Caucasians and from each other in their body mass index/body fat per cent relationship", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "35\u201338", "plainTextFormattedCitation" : "35\u201338", "previouslyFormattedCitation" : "35\u201338" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }35–38, and preferentially store fat in the deep subcutaneous and visceral depotsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0022112", "ISSN" : "1932-6203", "PMID" : "21829446", "abstract" : "OBJECTIVE: We sought to determine if differences in the distribution and characteristics of adipose tissue between South Asians and white Caucasians account for differences in risk factors for cardiovascular disease.\n\nRESEARCH DESIGN AND METHODS: We recruited 108 healthy South Asians (36.8 years) and white Caucasians (34.2 years) within three BMI strata. Body composition, adipocyte size, abdominal fat area, and hepatic adiposity were assessed and related to fasting glucose, insulin, lipids and adiponectin.\n\nRESULTS: After adjustment for age, sex, and BMI, South Asians compared to white Caucasians had higher ln fasting insulin (mean difference (MD): 0.44; 95% CI: 0.20-0.69), lower HDL cholesterol (md: -0.13; 95% CI:-0.26 to -0.01), and lower adiponectin (md: -2.38; 95% CI: -3.59 to -1.17). South Asians also had more body fat (md: 2.69; 95% CI: 0.70 to 4.69), lower lean muscle mass (md: -3.25; 95%CI: -5.35 to -1.14), increased waist to hip ratio (md: 0.03; 95% CI: 0.01-0.05), less superficial subcutaneous abdominal adipose tissue (md: -2.94; 95% CI: -5.56 to-0.32), more deep/visceral to superficial adipose tissue ratio (md 0.34; 95% CI: 0.02 to 0.65), and more liver fat (md: 7.43%; 95% CI: 2.30 to 12.55%). Adipocyte area was increased in South Asians compared to white Caucasians (md: 64.26; 95% CI: 24.3 to 104.1) units(2). Adjustment for adipocyte area attenuated the ethnic differences in insulin (md: 0.22; 95% CI: -0.07 to 0.51), HDL (md: -0.01; 95% CI: -0.16 to 0.13) and adiponectin (md: -1.11; 95% CI: -2.61 to 0.39). Adjustment for differences in adipocyte area and fat distribution attenuated the ethnic difference in liver fat (md: 5.19; 95% CI: 0.31 to 10.06).\n\nCONCLUSION: South Asians have an increased adipocyte area compared to white Caucasians. This difference accounts for the ethnic differences in insulin, HDL cholesterol, adiponectin, and ectopic fat deposition in the liver.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarnopolsky", "given" : "Mark A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rashid", "given" : "Shirya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schulze", "given" : "Karleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mente", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Sandy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Arya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Stanojevic", "given" : "Sanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e22112", "publisher" : "Public Library of Science", "title" : "Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE).", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "39", "plainTextFormattedCitation" : "39", "previouslyFormattedCitation" : "39" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39, versus white Caucasians, who store fat in the superficial regionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2010.94", "ISSN" : "1930-739X", "PMID" : "20448537", "abstract" : "South Asians have a higher prevalence of cardiovascular disease (CVD) than Europeans. Studies have identified distinct subcompartments of subcutaneous adipose tissue (SAT) that provide insight into the relationship between abdominal obesity and metabolic risk factors in different ethnic groups. Our objective was to determine the relationship between SAT compartments and fat-free mass (FFM) between South Asian and European cohorts, and between men and women. Healthy Europeans and South Asians (n = 408) were assessed for FFM via dual energy X-ray absorptiometry, and SAT areas by computed tomography (CT). SAT was subdivided into superficial subcutaneous abdominal adipose tissue (SSAT) and deep subcutaneous abdominal adipose tissue (DSAT). Linear regression analyses were performed using DSAT and SSAT as separate dependent variables and FFM and ethnicity as primary independent variables adjusting for age, gender, income, education, and smoking status. Results showed that South Asian men had significantly higher amounts of DSAT (median 187.65 cm(2) vs. 145.15 cm(2), P < 0.001), SSAT (median 92.0 cm(2) vs. 76.1 cm(2), P = 0.046), and body fat mass (BFM) (25.1 kg vs. 22.6 kg, P = 0.049) than European men. In a fully adjusted model, South Asians showed significantly greater DSAT at any FFM than Europeans. Women had more SSAT at any given FFM than men and less DSAT at any given FFM than men, irrespective of ethnic background. In conclusion, South Asians had more DSAT than Europeans and men had relatively more DSAT than women. These data suggest that specific fat depots are influenced by ethnicity and gender; therefore, could provide insight into the relationship between ethnicity, gender and subsequent risk for CVD.", "author" : [ { "dropping-particle" : "", "family" : "Kohli", "given" : "Simi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sniderman", "given" : "Allan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tchernof", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lear", "given" : "Scott A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity (Silver Spring, Md.)", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "2177-83", "title" : "Ethnic-specific differences in abdominal subcutaneous adipose tissue compartments.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "40", "plainTextFormattedCitation" : "40", "previouslyFormattedCitation" : "40" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }40. Taken together, these data support the contention that South Asians are comparably more adipose at the same BMI as white CaucasiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.231/JIM.0b013e3182650a09", "ISSN" : "1708-8267", "PMID" : "22914598", "abstract" : "BACKGROUND: South Asians have a high prevalence of insulin resistance, which predisposes to type 2 diabetes.\n\nRATIONALE: In the current study, we examined whether insulin sensitivity in South Asian men and men of European descent (Europids) relates to truncal and lower body fat, number of adipocytes, and cell size distribution.\n\nRESULTS: Fifteen South Asian men and 15 Europid young men with comparable body mass indexes completed assessments of insulin sensitivity, body composition analysis by dual-energy x-ray absorptiometry, and measurement of adipocyte cellularity in the subcutaneous abdominal (truncal) and gluteal (lower body) adipose tissue. The South Asians and the Europids had similar total body fat and fat contents in truncal and lower body regions. Compared to the Europids, the South Asians had a greater insulin resistance shown by fasting insulin, area-under-the-curve for postprandial insulin, oral glucose insulin sensitivity, homeostatic model assessment of insulin resistance, \u03b2-cell index, and triglyceride-to-high-density lipoprotein ratio. The South Asians had similar number of adipocytes to the Europids, but the South Asians had significantly higher ratios of small-to-larger adipocytes. The South Asians further had a higher fraction of very large adipocytes. In both South Asians and Europids, truncal fat was positively associated with insulin resistance. In the South Asians but not in the Europids, lower body fat was associated with severity of insulin resistance.\n\nCONCLUSIONS: The results suggest first, a higher ratio of small-to-larger adipocytes in the South Asians consistent with a lesser lipid storage capacity of adipose tissue; and second, the positive association of lower body fat with insulin resistance in the South Asians implies that fat in their lower body worsens insulin resistance. This association was not observed in the Europids.", "author" : [ { "dropping-particle" : "", "family" : "Balakrishnan", "given" : "Preetha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Arsalla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dunn", "given" : "Fredrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vega", "given" : "Gloria Lena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of investigative medicine : the official publication of the American Federation for Clinical Research", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2012", "10" ] ] }, "page" : "999-1004", "title" : "Influence of upper and lower body adipose tissue on insulin sensitivity in South Asian men.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "41", "plainTextFormattedCitation" : "41", "previouslyFormattedCitation" : "41" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }41.The differences among South Asians and white Caucasians are present in adolescence and at birthADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/jech.2010.112516", "ISSN" : "1470-2738", "PMID" : "21118952", "abstract" : "BACKGROUND: The mean birth weight of offspring of Bangladeshi, Indian and Pakistani women tends to be among the lowest of any ethnic groups regardless of country of residence. However, it is unclear whether the mean birth weight of South Asian offspring born in England and Wales is higher among those whose mothers were themselves born in England and Wales compared to those whose mothers were born in the Indian sub-continent.\n\nMETHODS: We used cross-sectional data from a unique linkage of routine records for the whole of England and Wales (2005-2006, n=861\u2008654) to estimate mean birth weights of the live singleton offspring of Bangladeshi, Indian, Pakistani or White British ethnicity according to whether maternal place of birth was England and Wales or the Indian sub-continent.\n\nRESULTS: Offspring of women born in the Indian sub-continent were slightly heavier at birth than offspring of South Asian women born in England and Wales even after adjustment for gestational age, maternal age and parity (Bangladeshi 28 g, 95% CI 10 to 46; Indian 31 g, 95% CI 20 to 42; Pakistani 21 g, 95% CI 12 to 29).\n\nCONCLUSIONS: There is no indication that the mean birth weight of South Asian offspring of women born in England and Wales is higher than the mean birth weight of those whose mothers were born in the Indian sub-continent. This suggests a shared physiological tendency for down-regulation of fetal growth transmissible across generations. Within the UK, there is unlikely to be any appreciable increase in mean birth weight of South Asian babies over the next few decades.", "author" : [ { "dropping-particle" : "", "family" : "Leon", "given" : "David A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moser", "given" : "Kath A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of epidemiology and community health", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "6" ] ] }, "page" : "544-51", "title" : "Low birth weight persists in South Asian babies born in England and Wales regardless of maternal country of birth. Slow pace of acculturation, physiological constraint or both? Analysis of routine data.", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0143-005X", "PMID" : "12177085", "abstract" : "OBJECTIVE: To assess differences in birth weight between all first and second generation South Asian babies born in Southampton, and trends since 1957.\n\nDESIGN: Retrospective, cohort study.\n\nSETTING: Birth records for babies born in Southampton from 1957 to 1996 were searched to identify all babies born of South Asian origin (including from the Indian subcontinent, East Africa, and elsewhere).\n\nMAIN OUTCOME MEASURES: All information recorded in the birth record about the mother and baby was extracted.\n\nRESULTS: 2395 full term (>37 weeks; mean birth weight 3110; 95%CI 3092 to 3129) singleton births were identified. Detailed analysis was restricted to mothers either born in the Indian subcontinent (India, Pakistan, or Bangladesh (1435)) or United Kingdom (283). Mean birth weight and % low birth weight (<2500 g) were 3133 g (95%CI 3108 to 3157) and 7.5%, for first generation babies and 3046 g (2992 to 3099) and 11.7% for second generation babies. There was no trend over time to increased average birth weight in either first or second generation babies. Adjusting for other factors that were statistically significantly related to birth weight (gender, gestational age, mother's age, maternal weight at 15 weeks, parity, and mother's ethnic group) did not alter the trends.\n\nCONCLUSIONS: For that group in the UK who derive from the Indian subcontinent, average birth weight is significantly less than the national average. There has not been any increase in the average birth weight over the past 40 years, and the birth weight of babies of women who were born in the UK are no greater. The persistence of lower than desirable birth weight may result long term in higher than average rates of diabetes and heart disease in these groups.", "author" : [ { "dropping-particle" : "", "family" : "Margetts", "given" : "B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohd Yusof", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dallal", "given" : "Z", "non-dropping-particle" : "Al", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of epidemiology and community health", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2002", "9" ] ] }, "page" : "684-7", "title" : "Persistence of lower birth weight in second generation South Asian babies born in the United Kingdom.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "1911-2092", "PMID" : "20101298", "abstract" : "BACKGROUND: Fetal growth restriction is associated with metabolic derangements in the newborn, impaired functioning in childhood and chronic diseases in adulthood. Differences between ethnic groups with respect to fetal growth may result in the misclassification of constitutionally small or large babies as having abnormal growth for their gestational age. We have developed intrauterine growth charts based on precise measurements of newborns whose parents were both of European, Chinese or South Asian ethnicity.\n\nMETHODS: Weight, length and head circumference were measured in 2695 infants born to healthy non-smoking mothers in British Columbia at 37-41 completed weeks of gestation. Gestational age was confirmed by ultrasound before 20 weeks of gestation. Weight was measured by digital scale, length by stadiometer and head circumference by firm plastic tape measures. Means and 95% confidence intervals were compared among newborns grouped by ethnicity and sex. Smoothed graphs were constructed for visual interpretation.\n\nRESULTS: At 40 weeks, infants of European descent (\"European\" infants) weighed 225.5 g more on average than infants of Chinese descent (\"Chinese\" infants) (p < 0.001) and 254.6 g more than infants of South Asian descent (\"South Asian\" infants) (p < 0.001). The mean difference in birth weight between Chinese and South Asian infants (19.1 g) was not statistically significant. The mean length of European infants at 40 weeks of gestation was 0.89 cm greater than that of Chinese infants (p < 0.001). Differences in mean length between European and South Asian babies or between Chinese and South Asian babies was not statistically significant. The mean head circumferance of European babies was 0.50 cm larger than that of Chinese babies at 40 weeks (p < 0.001) but did not differ significantly from that of South Asian babies. South Asian and Chinese babies had similar mean head circumferences at 40 weeks. When differences in mean birth weight, length and head circumference were examined within boys and girls, the observed differences according to ethnicity remained statistically significant.\n\nCONCLUSION: Important differences in weight, length and head circumferences are reported among babies according to ethnicity. The use of sex- and ethnicity-specific growth charts may prevent the misclassification of newborns as small or large for gestational age.", "author" : [ { "dropping-particle" : "", "family" : "Janssen", "given" : "Patricia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thiessen", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Michael C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitfield", "given" : "Michael F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Macnab", "given" : "Ying C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cullis-Kuhl", "given" : "Sue C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Open medicine : a peer-reviewed, independent, open-access journal", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "1" ] ] }, "page" : "e74-88", "title" : "Standards for the measurement of birth weight, length and head circumference at term in neonates of European, Chinese and South Asian ancestry.", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "42\u201344", "plainTextFormattedCitation" : "42\u201344", "previouslyFormattedCitation" : "42\u201344" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }42–44. Several cross-sectional and longitudinal studies show that South Asian children have greater %body fat with a higher degree of central adiposityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1464-5491.2005.01587.x", "ISSN" : "0742-3071", "PMID" : "16108862", "abstract" : "AIM: To examine whether plasma glucose, insulin resistance and markers of adiposity differed between British adolescents of South Asian and European origin. METHODS: School-based cross-sectional study (1998-2000), in which detailed measurements of adiposity, fasting plasma glucose and serum insulin were made in 90 South Asian and 1248 European pupils (overall 69% response rate). RESULTS: Compared with Europeans, South Asian subjects had higher mean fasting insulin levels (percentage mean difference 17.2%, 95% confidence interval 7.2-26.1%, P = 0.001), a higher mean fasting glucose (mean difference 0.19 mmol/l, 95% confidence interval 0.08-0.29 mmol/l, P = 0.0005) and a higher prevalence of impaired fasting glucose (> or = 6.1 mmol/l) (5.6% vs. 1.5%, odds ratio 3.9, 95% confidence interval 1.4-10.9, P = 0.004). Although South Asian children tended to have slightly higher indices of adiposity than Europeans (other than body mass index), the differences in glucose and insulin levels persisted after adjustment for adiposity and for pubertal status. CONCLUSIONS: The predisposition to Type 2 diabetes observed in South Asian adults is apparent before adult life. Establishing the contributions of the childhood and fetal environments and of genetic factors to the development of these ethnic differences is an important priority. Prevention of Type 2 diabetes in British South Asians needs to begin before adult life.", "author" : [ { "dropping-particle" : "", "family" : "Whincup", "given" : "P H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilg", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Odoki", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alberti", "given" : "K G M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2005", "9" ] ] }, "page" : "1275-7", "title" : "British South Asians aged 13-16 years have higher fasting glucose and insulin levels than Europeans.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/oby.20483", "ISSN" : "1930-739X", "PMID" : "23596082", "abstract" : "OBJECTIVE: To examine whether periadolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults.\n\nDESIGN AND METHODS: Family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-\u03b1, and adiponectin) were examined in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other).\n\nRESULTS: Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance.\n\nCONCLUSIONS: Children show some of the same racial/ethnic differences in risk factors for adiposity-related comorbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related comorbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history.", "author" : [ { "dropping-particle" : "", "family" : "Rosenbaum", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fennoy", "given" : "Ilene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Accacha", "given" : "Siham", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carey", "given" : "Dennis E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holleran", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rapaport", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shelov", "given" : "Steven P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speiser", "given" : "Phyllis W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ten", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhangoo", "given" : "Amrit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boucher-Berry", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Espinal", "given" : "Yomery", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rishi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassoun", "given" : "Abeer A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iazetti", "given" : "Loretta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jean-Jacques", "given" : "Fabienne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jean", "given" : "Amy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Michelle L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Robet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowell", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michel", "given" : "Lesley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenfeld", "given" : "Warren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity (Silver Spring, Md.)", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "10" ] ] }, "page" : "2081-90", "title" : "Racial/ethnic differences in clinical and biochemical type 2 diabetes mellitus risk factors in children.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1089/dia.2012.0236", "ISSN" : "1557-8593", "PMID" : "23151017", "abstract" : "AIM: This study was designed to determine the prevalence of glucose intolerance (prediabetes or diabetes) in children and adolescents in urban South India.\n\nSUBJECTS AND METHODS: Children (6-11 years old) and adolescents (12-19 years old) (n=1,519; 777 boys and 742 girls) were randomly selected from residential apartments representing the 10 corporation zones of Chennai city. Height, weight, waist circumference, body fat percentage, and blood pressure were measured using standardized techniques. Investigations included oral glucose tolerance test (OGTT), lipid profile, and fasting insulin. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA-IR).\n\nRESULTS: The overall prevalence of glucose intolerance was 3.7% but was higher in girls compared with boys (4.2% vs. 3.2%, P<0.001) and increased to 12.7% in girls with abdominal obesity. On univariate regression, the following risk factors showed significant association with glucose intolerance in girls: adolescent age group (odds ratio [OR] 2.94; confidence interval (CI) 1.12, 7.76), waist circumference (OR 4.45; CI 1.95, 10.14), body mass index (OR 2.73; CI 1.32, 5.65), acanthosis nigricans (OR 2.35; CI 1.14, 4.83), family history of diabetes (OR 2.52; CI 1.07, 5.92), and HOMA-IR (OR 9.30; CI 3.59, 24.12). On multivariate analysis, only family history of diabetes (OR 4.11; CI 1.28, 13.22; P=0.018) and HOMA-IR (OR 11.22; CI 4.19, 30.05; P<0.001) remained significant. In boys only HOMA-IR (OR 5.19; CI 1.54, 17.44; P=0.008) was associated with glucose intolerance.\n\nCONCLUSIONS: The prevalence of glucose intolerance is high in Asian Indian adolescents, particularly in girls with abdominal obesity.", "author" : [ { "dropping-particle" : "", "family" : "Ranjani", "given" : "Harish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonya", "given" : "Jagadesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anjana", "given" : "Ranjit M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes technology & therapeutics", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "13-9", "title" : "Prevalence of glucose intolerance among children and adolescents in urban South India (ORANGE-2).", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1136/adc.2007.117911", "ISSN" : "1468-2044", "PMID" : "17522163", "abstract" : "BACKGROUND: There are known to be ethnic differences in body composition in adults which are related to ethnic differences in adult disease.\n\nOBJECTIVES: To evaluate gender and ethnic differences in percentage body fat in British schoolchildren and to compare these differences with classification of obesity using body mass index (BMI) criteria.\n\nDESIGN: A cross-sectional study of 1251 healthy children and adolescents aged 5-18 years from white, South Asian and African-Caribbean ethnic groups. Percentage body fat was determined by dual x ray absorptiometry and the subjects classified using BMI criteria for overweight and obesity.\n\nRESULTS: Significant gender differences in percentage body fat were seen, with girls having higher values from the age of 5 years. Girls had 3.8% higher percentage body fat at 5 years of age increasing to 12.9% at 18 years of age. Significant ethnic differences were found, with South Asian girls and boys having the highest percentage body fat from 5 and 7 years of age, respectively. These differences increased with age, being most significant in the teenage years. Although South Asian girls and boys were over-represented in the group containing children with more than 25% body fat (p<0.0001, chi2 test), African-Caribbean subjects were more likely to be classified as obese using BMI criteria.\n\nCONCLUSIONS: There are clear gender and ethnic differences in percentage body fat in British schoolchildren which may relate to known differences in the risk of type 2 diabetes in adolescence and adulthood. BMI criteria for defining overweight and obesity do not accurately identify ethnic differences in body fat.", "author" : [ { "dropping-particle" : "", "family" : "Shaw", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crabtree", "given" : "Nicola J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kibirige", "given" : "Mohammed S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fordham", "given" : "John N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of disease in childhood", "id" : "ITEM-4", "issue" : "10", "issued" : { "date-parts" : [ [ "2007", "10" ] ] }, "page" : "872-5", "title" : "Ethnic and gender differences in body fat in British schoolchildren as measured by DXA.", "type" : "article-journal", "volume" : "92" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "45\u201348", "plainTextFormattedCitation" : "45\u201348", "previouslyFormattedCitation" : "45\u201348" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }45–48, and a higher prevalence of impaired glucose toleranceADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa012578", "ISSN" : "1533-4406", "PMID" : "11893791", "abstract" : "BACKGROUND: Childhood obesity, epidemic in the United States, has been accompanied by an increase in the prevalence of type 2 diabetes among children and adolescents. We determined the prevalence of impaired glucose tolerance in a multiethnic cohort of 167 obese children and adolescents. METHODS: All subjects underwent a two-hour oral glucose-tolerance test (1.75 g [DOSAGE ERROR CORRECTED] of glucose per kilogram of body weight), and glucose, insulin, and C-peptide levels were measured. Fasting levels of proinsulin were obtained, and the ratio of proinsulin to insulin was calculated. Insulin resistance was estimated by homeostatic model assessment, and beta-cell function was estimated by calculating the ratio between the changes in the insulin level and the glucose level during the first 30 minutes after the ingestion of glucose. RESULTS: Impaired glucose tolerance was detected in 25 percent of the 55 obese children (4 to 10 years of age) and 21 percent of the 112 obese adolescents (11 to 18 years of age); silent type 2 diabetes was identified in 4 percent of the obese adolescents. Insulin and C-peptide levels were markedly elevated after the glucose-tolerance test in subjects with impaired glucose tolerance but not in adolescents with diabetes, who had a reduced ratio of the 30-minute change in the insulin level to the 30-minute change in the glucose level. After the body-mass index had been controlled for, insulin resistance was greater in the affected cohort and was the best predictor of impaired glucose tolerance. CONCLUSIONS: Impaired glucose tolerance is highly prevalent among children and adolescents with severe obesity, irrespective of ethnic group. Impaired oral glucose tolerance was associated with insulin resistance while beta-cell function was still relatively preserved. Overt type 2 diabetes was linked to beta-cell failure.", "author" : [ { "dropping-particle" : "", "family" : "Sinha", "given" : "Ranjana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisch", "given" : "Gene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teague", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Tamborlane", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banyas", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allen", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Savoye", "given" : "Mary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rieger", "given" : "Vera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taksali", "given" : "Sara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbetta", "given" : "Gina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherwin", "given" : "Robert S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caprio", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England journal of medicine", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2002", "3", "14" ] ] }, "page" : "802-10", "title" : "Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.", "type" : "article-journal", "volume" : "346" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1464-5491.2005.01587.x", "ISSN" : "0742-3071", "PMID" : "16108862", "abstract" : "AIM: To examine whether plasma glucose, insulin resistance and markers of adiposity differed between British adolescents of South Asian and European origin. METHODS: School-based cross-sectional study (1998-2000), in which detailed measurements of adiposity, fasting plasma glucose and serum insulin were made in 90 South Asian and 1248 European pupils (overall 69% response rate). RESULTS: Compared with Europeans, South Asian subjects had higher mean fasting insulin levels (percentage mean difference 17.2%, 95% confidence interval 7.2-26.1%, P = 0.001), a higher mean fasting glucose (mean difference 0.19 mmol/l, 95% confidence interval 0.08-0.29 mmol/l, P = 0.0005) and a higher prevalence of impaired fasting glucose (> or = 6.1 mmol/l) (5.6% vs. 1.5%, odds ratio 3.9, 95% confidence interval 1.4-10.9, P = 0.004). Although South Asian children tended to have slightly higher indices of adiposity than Europeans (other than body mass index), the differences in glucose and insulin levels persisted after adjustment for adiposity and for pubertal status. CONCLUSIONS: The predisposition to Type 2 diabetes observed in South Asian adults is apparent before adult life. Establishing the contributions of the childhood and fetal environments and of genetic factors to the development of these ethnic differences is an important priority. Prevention of Type 2 diabetes in British South Asians needs to begin before adult life.", "author" : [ { "dropping-particle" : "", "family" : "Whincup", "given" : "P H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilg", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Odoki", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alberti", "given" : "K G M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2005", "9" ] ] }, "page" : "1275-7", "title" : "British South Asians aged 13-16 years have higher fasting glucose and insulin levels than Europeans.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/oby.20483", "ISSN" : "1930-739X", "PMID" : "23596082", "abstract" : "OBJECTIVE: To examine whether periadolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults.\n\nDESIGN AND METHODS: Family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-\u03b1, and adiponectin) were examined in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other).\n\nRESULTS: Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance.\n\nCONCLUSIONS: Children show some of the same racial/ethnic differences in risk factors for adiposity-related comorbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related comorbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history.", "author" : [ { "dropping-particle" : "", "family" : "Rosenbaum", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fennoy", "given" : "Ilene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Accacha", "given" : "Siham", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "Lisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carey", "given" : "Dennis E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holleran", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rapaport", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shelov", "given" : "Steven P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speiser", "given" : "Phyllis W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ten", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhangoo", "given" : "Amrit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boucher-Berry", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Espinal", "given" : "Yomery", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Rishi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassoun", "given" : "Abeer A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iazetti", "given" : "Loretta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jean-Jacques", "given" : "Fabienne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jean", "given" : "Amy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klein", "given" : "Michelle L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Robet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lowell", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Michel", "given" : "Lesley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenfeld", "given" : "Warren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity (Silver Spring, Md.)", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "10" ] ] }, "page" : "2081-90", "title" : "Racial/ethnic differences in clinical and biochemical type 2 diabetes mellitus risk factors in children.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1530/eje.0.1510199", "ISSN" : "0804-4643", "abstract" : "BACKGROUND: The incidence of childhood obesity and type 2 diabetes is an increasing problem in Europe. We determined the prevalence of impaired glucose regulation in a predominantly Caucasian cohort of 491 children and adolescents with obesity. METHODS: Fasting glucose and insulin levels were determined in all 491 subjects. Patients with an abnormal fasting glucose or with additional risk factors (positive family history of type 2 diabetes, acanthosis nigricans, hyperlipidemia; n=102) underwent an oral glucose tolerance test (OGTT; 1.75 g glucose/kg body weight). Homeostasis model assessment was used to estimate insulin resistance in all subjects. The insulin sensitivity index was determined in those subjects who underwent an OGTT. Screening for mutations in the melanocortin 4 receptor (MC4R) gene and the coding region of the brain-derived neutrophic factor (BDNF) in 37 patients with an impaired glucose tolerance was performed by WAVE analysis. RESULTS: Out of the total of 491 patients, 12 had an abnormal fasting glucose level. Of the 102 patients who underwent an OGTT, 37 had impaired glucose tolerance; 6 out of the 102 patients were diagnosed with type 2 diabetes. Eighty-eight per cent of patients with abnormal glucose tolerance and 66% of patients with type 2 diabetes were Caucasian. Insulin resistance indices correlated well with the degree of abnormal glucose tolerance. Using the screening algorithm for type 2 diabetes as advocated by the American Diabetes Association, 68% of patients with impaired glucose tolerance and 66% of patients with type 2 diabetes would have been missed. No abnormalities in the MC4R and BDNF genes were detected. CONCLUSIONS: Impaired glucose tolerance and type 2 diabetes are far more common in obese European children of Caucasian origin than previously thought. Using fasting glucose levels as the main screening tool appears to be insufficient in detecting these children.", "author" : [ { "dropping-particle" : "", "family" : "Wiegand", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maikowski", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blankenstein", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biebermann", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarnow", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gruters", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Endocrinology", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2004", "8", "1" ] ] }, "page" : "199-206", "title" : "Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity -- a problem that is no longer restricted to minority groups", "type" : "article-journal", "volume" : "151" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1089/dia.2012.0236", "ISSN" : "1557-8593", "PMID" : "23151017", "abstract" : "AIM: This study was designed to determine the prevalence of glucose intolerance (prediabetes or diabetes) in children and adolescents in urban South India.\n\nSUBJECTS AND METHODS: Children (6-11 years old) and adolescents (12-19 years old) (n=1,519; 777 boys and 742 girls) were randomly selected from residential apartments representing the 10 corporation zones of Chennai city. Height, weight, waist circumference, body fat percentage, and blood pressure were measured using standardized techniques. Investigations included oral glucose tolerance test (OGTT), lipid profile, and fasting insulin. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA-IR).\n\nRESULTS: The overall prevalence of glucose intolerance was 3.7% but was higher in girls compared with boys (4.2% vs. 3.2%, P<0.001) and increased to 12.7% in girls with abdominal obesity. On univariate regression, the following risk factors showed significant association with glucose intolerance in girls: adolescent age group (odds ratio [OR] 2.94; confidence interval (CI) 1.12, 7.76), waist circumference (OR 4.45; CI 1.95, 10.14), body mass index (OR 2.73; CI 1.32, 5.65), acanthosis nigricans (OR 2.35; CI 1.14, 4.83), family history of diabetes (OR 2.52; CI 1.07, 5.92), and HOMA-IR (OR 9.30; CI 3.59, 24.12). On multivariate analysis, only family history of diabetes (OR 4.11; CI 1.28, 13.22; P=0.018) and HOMA-IR (OR 11.22; CI 4.19, 30.05; P<0.001) remained significant. In boys only HOMA-IR (OR 5.19; CI 1.54, 17.44; P=0.008) was associated with glucose intolerance.\n\nCONCLUSIONS: The prevalence of glucose intolerance is high in Asian Indian adolescents, particularly in girls with abdominal obesity.", "author" : [ { "dropping-particle" : "", "family" : "Ranjani", "given" : "Harish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonya", "given" : "Jagadesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anjana", "given" : "Ranjit M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes technology & therapeutics", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "13-9", "title" : "Prevalence of glucose intolerance among children and adolescents in urban South India (ORANGE-2).", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "45\u201347,49,50", "plainTextFormattedCitation" : "45\u201347,49,50", "previouslyFormattedCitation" : "45\u201347,49,50" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }45–47,49,50. Similar observations are evident in South Asian youth from studies around the world and the findings seem to be generalizable globally. Peters & Ulijaszek concluded that South Asian children deposit more fat on the trunk and less on upper limb compared to white Caucasians after studying subscapular and tricep skinfold thickness in 2,224 children in EnglandADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0301-4460", "PMID" : "1734819", "abstract" : "Arm circumference, triceps and subscapular skinfold thicknesses of 2224 Indo-Pakistani children aged 3-10.9 years living in Nottingham and Leicestershire were measured. The children were classified into populations according to country of origin, and religion, prior to analysis. Significant between-population differences were shown for all three variables, the effect being stronger in males than in females. Sex differences in arm circumference and triceps skinfold thickness were greater than those found in the British reference populations, whilst the patterns of fat distribution differed from the British standards for all the Indo-Pakistani populations, male and female.", "author" : [ { "dropping-particle" : "", "family" : "Peters", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ulijaszek", "given" : "S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of human biology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "17-22", "title" : "Population and sex differences in arm circumference and skinfold thicknesses among Indo-Pakistani children living in the East Midlands of Britain.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "51", "plainTextFormattedCitation" : "51", "previouslyFormattedCitation" : "51" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }51. Gulliford reported similar results in children of South Asian descent in TrinidadADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0300-5771", "PMID" : "11689509", "abstract" : "BACKGROUND: To evaluate distribution of body mass index (BMI) and subcutaneous fat in children of African or Indian subcontinent descent living in Trinidad and Tobago.\n\nMETHODS: A cross-sectional survey was carried out in a nationally representative sample of 66 government schools. Measurements were made of children's heights, weights, triceps and subscapular skinfold thicknesses. Data were analysed by sex and ethnic group and comparison was made with international standards for overweight and obesity and with British (1990) reference curves for BMI.\n\nRESULTS: Data were analysed for 5688/6731 (85%) eligible children including 1934 Afro-Trinidadian, 1689 Indo-Trinidadian, and 1794 of mixed ethnicity. Afro-Trinidadian and mixed children were taller, but Indo-Trinidadian children were shorter than reference. Values for BMI were lower than reference: mean standard deviation score (SDS), (95% confidence interval) Afro-Trinidadian -0.34 (-0.39 to -0.28), Indo-Trinidadian -1.32 (-1.39 to -1.25), mixed -0.67 (-0.74 to -0.61). Overall 486 (8.5%, 7.8 to 9.3%) of children were overweight and 138 (2.4%, 2.0 to 2.9%) were obese. Triceps skinfold thickness values were lower than reference (-0.45, -0.48 to -0.42 SDS) but subscapular skinfold thicknesses were higher (0.45, 0.43 to 0.47 SDS). Higher BMI were associated with higher BMI in the child's parents, higher reported birthweight, older age of the child's mother, smaller family size, and with higher maternal educational attainment.\n\nCONCLUSIONS: Overweight was prevalent and distribution of subcutaneous fat was central. Work is needed to determine whether these findings are associated with adult patterns of fat distribution and metabolic abnormalities.", "author" : [ { "dropping-particle" : "", "family" : "Gulliford", "given" : "M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahabir", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocke", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chinn", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rona", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2001", "10" ] ] }, "page" : "989-98", "title" : "Overweight, obesity and skinfold thicknesses of children of African or Indian descent in Trinidad and Tobago.", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "52", "plainTextFormattedCitation" : "52", "previouslyFormattedCitation" : "52" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }52. Similarly, at birth, South Asians appear to be smaller but with relatively more adipose tissue, measured using skinfold thickness and adipose tissue volume with an MRIADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ije/dys139", "ISSN" : "1464-3685", "PMID" : "22984147", "abstract" : "BACKGROUND: South Asian children and adults have a more adipose body composition compared with those of European ancestry. This is thought to be related to their increased risk of metabolic disorders. However, little is known about how early in life such differences are manifest.\n\nOBJECTIVE: To determine whether there are differences in fat mass (FM) and fat-free mass (FFM) between UK-born South Asians and White Europeans in infancy. Design A cross-sectional study of 30 South Asian and 30 White European infants aged 6-12 weeks. Mothers were recruited from clinics in London, and infants' FM and FFM were determined using air-displacement plethysmography (PeaPod(\u00ae)).\n\nRESULTS: In early infancy South Asians had less FFM than White Europeans [0.34 kg less, 95% confidence interval (CI): 0.15, 0.52], with a considerably weaker indication of them also having more FM (0.02 kg more, 95% CI: -0.14, 0.18). These differences persisted when the overall smaller body size of South Asian infants was taken into account. For a given total infant weight, the balance of body composition of South Asians was shifted by 0.16 kg (95% CI: 0.06, 0.25) from FFM to FM. The ethnic differences in the amount of FFM were almost completely accounted for by ethnic differences in the rate of growth in utero and length of gestation.\n\nCONCLUSIONS: The characteristic differences in body composition observed between adult South Asians and White Europeans are apparent in early infancy. Of particular note is that this is the first study to demonstrate that South Asians compared with White Europeans have reduced FFM in infancy. The early manifestation of this phenotype suggests that it is either genetic and/or determined through exposure to maternal physiology, rather than a consequence of behaviours or diet in childhood or at older ages.", "author" : [ { "dropping-particle" : "", "family" : "Stanfield", "given" : "Kristina M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wells", "given" : "Jonathan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fewtrell", "given" : "Mary S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frost", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leon", "given" : "David A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "page" : "1409-18", "title" : "Differences in body composition between infants of South Asian and European ancestry: the London Mother and Baby Study.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1203/PDR.0b013e31819d98be", "ISSN" : "0031-3998", "abstract" : "Abdominal adiposity and metabolic ill health in Asian Indians are a growing public health concern. Causal pathways are unknown. Preventive measures in adults have had limited success. The aim of this observational case-control study was to compare adipose tissue partitioning in 69 healthy full term Asian Indian and white European newborns born in Pune, India and London, UK, respectively. The main outcome measures were total and regional adipose tissue content measured by whole body magnetic resonance imaging. Although smaller in weight (95% CI for difference \u22120.757 to \u22120.385 kg, p < 0.001), head circumference (\u22122.15 to \u22120.9 cm, p < 0.001), and length (\u22122.9 to \u22121.1 cm p < 0.001), the Asian Indian neonates had significantly greater absolute adiposity in all three abdominal compartments, internal (visceral) (0.012\u20130.023 L, p < 0.001), deep s.c. (0.003\u20130.017 L, p = 0.006) and superficial s.c. (0.006\u20130.043 L, p = 0.011) and a significant reduction in nonabdominal superficial s.c. adipose tissue (\u22120.184 to \u22120.029 L, p = 0.008) in comparison to the white European babies despite similar whole body adipose tissue content (\u22120.175 to 0.034 L, p = 0.2). We conclude that differences in adipose tissue partitioning exist at birth. Investigative, screening, and preventive measures must involve maternal health, intrauterine life, and infancy.", "author" : [ { "dropping-particle" : "", "family" : "Modi", "given" : "Neena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "E Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uthaya", "given" : "Sabita N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umranikar", "given" : "Shalini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "Jimmy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "Chittaranjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Research", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5" ] ] }, "page" : "584-587", "publisher" : "International Pediatrics Research Foundation, Inc.", "title" : "Whole Body Magnetic Resonance Imaging of Healthy Newborn Infants Demonstrates Increased Central Adiposity in Asian Indians", "title-short" : "Pediatr Res", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1210/jc.2002-020434", "ISSN" : "0021-972X", "abstract" : "We studied body size and cord blood leptin and insulin concentrations in newborn urban Indian (Pune, India) and white Caucasian (London, UK) babies to test the hypothesis that the adiposity and hyperinsulinemia of Indians are present at birth. Indian babies (n = 157) were lighter in weight compared with white Caucasian babies [n = 67; median weight, 2805 g vs. 3475 g, respectively; P < 0.001, adjusted for gestational age and sex; \u22121.52 sd score; confidence interval (CI), \u22121.66, \u22121.42] and had smaller abdominal (\u22122.39 sd score; CI, \u22122.52, \u22122.09), midarm (\u22121.47 sd score; CI, \u22121.58, \u22121.34), and head (\u22121.23 sd score; CI, \u22121.42, \u22121.13) circumferences. However, their skinfolds were relatively preserved: subscapular (central) skinfold (\u22120.32 sd score; CI, \u22120.43, \u22120.20) was better preserved than triceps (peripheral) skinfold (\u22120.86 sd score; CI, \u22120.97, \u22120.75). Cord plasma leptin (median, 6.2 ng/ml Pune and 6.4 ng/ml London) and insulin (median, 34.7 pmol/liter Pune and 20.8 pmol/liter London) concentrations were ...", "author" : [ { "dropping-particle" : "", "family" : "Yajnik", "given" : "C. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lubree", "given" : "H. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rege", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naik", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshpande", "given" : "J. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshpande", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Joglekar", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yudkin", "given" : "J. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Clinical Endocrinology & Metabolism", "id" : "ITEM-3", "issue" : "12", "issued" : { "date-parts" : [ [ "2002", "12", "2" ] ] }, "language" : "en", "page" : "5575-5580", "publisher" : "Endocrine Society", "title" : "Adiposity and Hyperinsulinemia in Indians Are Present at Birth", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1093/ije/dyq180", "ISSN" : "1464-3685", "PMID" : "21044977", "abstract" : "BACKGROUND: The objective of this study was to examine adiposity patterns in UK South Asian, black African-Caribbean and white European children using a range of adiposity markers. A cross-sectional survey in London, Birmingham and Leicester primary schools was conducted. Weight, height, waist circumference, skinfold thickness values (biceps, triceps, subscapular and suprailiac) were measured. Fat mass was derived from bioimpedance; optimally height-standardized indices were derived for all adiposity markers. Ethnic origin was based on parental self-report. Multilevel models were used to obtain adjusted means and ethnic differences adjusted for gender, age, month, observer and school (fitted as a random effect). A total of 5887 children aged 9-10 years participated (response rate 68%), including 1345 white Europeans, 1523 South Asians and 1570 black African-Caribbeans.\n\nRESULTS: Compared with white Europeans, South Asians had a higher sum of all skinfolds and fat mass percentage, and their body mass index (BMI) was lower. South Asians were slightly shorter but use of optimally height-standardized indices did not materially affect these comparisons. At any given fat mass, BMI was lower in South Asians than white Europeans. In similar comparisons, black African-Caribbeans had a lower sum of all skinfolds but a higher fat mass percentage, and their BMI was higher. Black African-Caribbeans were markedly taller. Use of optimally height-standardized indices yielded markedly different findings; sum of skinfolds index was markedly lower, whereas fat mass index and weight-for-height index were similar. At any given fat mass, BMI was similar in black African-Caribbeans and white Europeans.\n\nCONCLUSIONS: UK South Asian children have higher adiposity levels and black African-Caribbeans have similar or lower adiposity levels when compared with white Europeans. However, these differences are not well represented by comparisons based on BMI, which systematically underestimates adiposity in South Asians, and in black African-Caribbeans it overestimates adiposity because of its association with height.", "author" : [ { "dropping-particle" : "", "family" : "Nightingale", "given" : "Claire M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudnicka", "given" : "Alicja R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Chris G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "Derek G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whincup", "given" : "Peter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "2", "1" ] ] }, "page" : "33-44", "title" : "Patterns of body size and adiposity among UK children of South Asian, black African-Caribbean and white European origin: Child Heart And health Study in England (CHASE Study).", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "53\u201356", "plainTextFormattedCitation" : "53\u201356", "previouslyFormattedCitation" : "53\u201356" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }53–56. On a global scale, the prevalence of low birth weight (LBW) is highest in the South Asian region, with India accounting for nearly 40% of global LBW infantsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12098-010-0038-9", "ISSN" : "0973-7693", "PMID" : "20414750", "abstract" : "India recognized the importance of improving the health and nutritional status of children, and initiated steps to improve access to nutrition and health services soon after independence. Over the years, the infrastructure and human resources for manning the health and nutrition services have been built up and currently cover the entire country. However these are inadequacies in terms of content and quality of services and undernutrition rates and under five morality rates continue to be high. Undernutrition begins in utero, and with low birthweight, effective antenatal care can help in reducing low birth weight. The poor infant and young child feeding (IYCF) practices, repeated morbidity due to infections and poor utilization of health and nutrition services are other causes of undernutrition in children in India. The key intervention to prevent undernutrition is nutritional and health education through all modes of communication, to bring about is a behavioral change towards appropriate IYCF and utilization of health care. Appropriate convergence and synergy between health and nutrition functionaries can play a major role in early detection and effective management of both undernutrition and infections, accelerate the pace of reduction in both undernutrition and under five mortality and enable India to reach Millennium Development Goals.", "author" : [ { "dropping-particle" : "", "family" : "Ramachandran", "given" : "Prema", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Indian journal of pediatrics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "301-5", "title" : "Nutrition and child survival in India.", "type" : "article-journal", "volume" : "77" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "57", "plainTextFormattedCitation" : "57", "previouslyFormattedCitation" : "57" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }57. Of particular importance are the observations that the afore-described differences persist in South Asians even after several generations in ‘Western’ countriesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.9778/cmajo.20130064", "ISSN" : "2291-0026", "PMID" : "25295238", "abstract" : "BACKGROUND: South Asians represent about 3% of the Canadian population and have a higher burden of certain cardiovascular risk factors and cardiovascular disease (CVD) compared with white people. The objective of this study was to review the literature to compare cardiovascular risk factors and disease management practices among adult South Asian and white Canadians.\n\nMETHODS: We searched MEDLINE, Embase, Cochrane and Cumulative Index to Nursing and Allied Health Literature databases from their inception through Feb. 17, 2014 and the reference lists of the selected articles. English-language studies of interventions and observational studies of biological mechanisms underlying CVD risk in South Asians conducted in Canada were eligible for inclusion. Where appropriate, we used random-effects meta-analyses to integrate results comparing the CVD risk profiles of South Asian and white Canadians.\n\nRESULTS: We included 50 articles (n = 5\u00a0805\u00a0313 individuals) in this review. Compared with white Canadians, South Asian Canadians had a higher prevalence and incidence of CVD, an increased prevalence of diabetes (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.81 to 2.80, p\u00a0<\u00a00.001) and hypertension (OR 1.11, 95% CI 1.02 to 1.22, p\u00a0=\u00a00.02), lower high-density lipoprotein cholesterol levels (mean difference -0.19\u00a0mmol/L, 95% CI -0.25 to -0.13 mmol/L, p\u00a0<\u00a00.001) and a higher percentage of body fat (men: absolute mean difference 3.23%, 95% CI 0.83% to 5.62%, p\u00a0=\u00a00.008; women: absolute mean difference 4.09%, 95% CI 3.46% to 4.72%, p\u00a0<\u00a00.001). South Asian people are also more sedentary, consume higher levels of carbohydrates and are less likely to smoke tobacco (OR 0.38, 95% CI 0.24 to 0.60, p\u00a0<\u00a00.001]) than white Canadians. No differences in access to diagnostic tests, outcomes following cardiovascular surgery or use of cardiac rehabilitation programs were apparent.\n\nINTERPRETATION: Compared with white people, South Asian people living in Canada have a higher prevalence and incidence of CVD and possess a unique cardiovascular risk profile.", "author" : [ { "dropping-particle" : "", "family" : "Rana", "given" : "Ayesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Russell J", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kandasamy", "given" : "Sujane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lear", "given" : "Scott A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CMAJ open", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "7" ] ] }, "page" : "E183-91", "title" : "Cardiovascular risk among South Asians living in Canada: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/(SICI)1096-9136(199801)15:1<53::AID-DIA521>3.0.CO;2-V", "ISSN" : "0742-3071", "PMID" : "9472864", "abstract" : "Over 20% of middle aged and elderly South Asian people throughout the world have diabetes. The associated mortality and morbidity risks are unclear. We compared mortality and morbidity in a cohort of South Asian and European people with diabetes in London, UK, in an 11-year follow-up of a population-based sample of 730 South Asians (mean age 55 in 1984) and 304 Europeans (mean age 67 in 1984) with diabetes aged 30 years and above in 1984. By 1995, 242 (33%) of South Asians, and 172 (57%) of Europeans had died. The all-cause mortality rate ratio (South Asian versus European) was 1.50 (95% CI 0.72-3.12) for those aged 30-54 years at baseline. Ethnic differences in mortality rates were abolished or reversed in people aged 65 years and above at baseline. The mortality rate ratio for circulatory deaths was 1.80 (95% CI 1.03-3.16, p < 0.05) and for heart disease was 2.02 (95% CI 1.04-3.92, p < 0.05) in those aged 30-64 years at baseline. Seventy-seven per cent of South Asian deaths were caused by circulatory disease, compared with 46% of European deaths. South Asian survivors were 3.8 times (95% CI 1.8-8.0, p = 0.001) more likely to report a history of myocardial infarction than Europeans. South Asian adults with diabetes show a markedly increased predisposition to cardiovascular disease compared with Europeans, especially in younger people. This emphasizes the urgent need to reduce cardiovascular risk in this vulnerable group.", "author" : [ { "dropping-particle" : "", "family" : "Mather", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fuller", "given" : "J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "1998", "1" ] ] }, "page" : "53-9", "title" : "Mortality and morbidity from diabetes in South Asians and Europeans: 11-year follow-up of the Southall Diabetes Survey, London, UK.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/ije/dyq180", "ISSN" : "1464-3685", "PMID" : "21044977", "abstract" : "BACKGROUND: The objective of this study was to examine adiposity patterns in UK South Asian, black African-Caribbean and white European children using a range of adiposity markers. A cross-sectional survey in London, Birmingham and Leicester primary schools was conducted. Weight, height, waist circumference, skinfold thickness values (biceps, triceps, subscapular and suprailiac) were measured. Fat mass was derived from bioimpedance; optimally height-standardized indices were derived for all adiposity markers. Ethnic origin was based on parental self-report. Multilevel models were used to obtain adjusted means and ethnic differences adjusted for gender, age, month, observer and school (fitted as a random effect). A total of 5887 children aged 9-10 years participated (response rate 68%), including 1345 white Europeans, 1523 South Asians and 1570 black African-Caribbeans.\n\nRESULTS: Compared with white Europeans, South Asians had a higher sum of all skinfolds and fat mass percentage, and their body mass index (BMI) was lower. South Asians were slightly shorter but use of optimally height-standardized indices did not materially affect these comparisons. At any given fat mass, BMI was lower in South Asians than white Europeans. In similar comparisons, black African-Caribbeans had a lower sum of all skinfolds but a higher fat mass percentage, and their BMI was higher. Black African-Caribbeans were markedly taller. Use of optimally height-standardized indices yielded markedly different findings; sum of skinfolds index was markedly lower, whereas fat mass index and weight-for-height index were similar. At any given fat mass, BMI was similar in black African-Caribbeans and white Europeans.\n\nCONCLUSIONS: UK South Asian children have higher adiposity levels and black African-Caribbeans have similar or lower adiposity levels when compared with white Europeans. However, these differences are not well represented by comparisons based on BMI, which systematically underestimates adiposity in South Asians, and in black African-Caribbeans it overestimates adiposity because of its association with height.", "author" : [ { "dropping-particle" : "", "family" : "Nightingale", "given" : "Claire M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudnicka", "given" : "Alicja R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Chris G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "Derek G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whincup", "given" : "Peter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "2", "1" ] ] }, "page" : "33-44", "title" : "Patterns of body size and adiposity among UK children of South Asian, black African-Caribbean and white European origin: Child Heart And health Study in England (CHASE Study).", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1136/jech.2010.112516", "ISSN" : "1470-2738", "PMID" : "21118952", "abstract" : "BACKGROUND: The mean birth weight of offspring of Bangladeshi, Indian and Pakistani women tends to be among the lowest of any ethnic groups regardless of country of residence. However, it is unclear whether the mean birth weight of South Asian offspring born in England and Wales is higher among those whose mothers were themselves born in England and Wales compared to those whose mothers were born in the Indian sub-continent.\n\nMETHODS: We used cross-sectional data from a unique linkage of routine records for the whole of England and Wales (2005-2006, n=861\u2008654) to estimate mean birth weights of the live singleton offspring of Bangladeshi, Indian, Pakistani or White British ethnicity according to whether maternal place of birth was England and Wales or the Indian sub-continent.\n\nRESULTS: Offspring of women born in the Indian sub-continent were slightly heavier at birth than offspring of South Asian women born in England and Wales even after adjustment for gestational age, maternal age and parity (Bangladeshi 28 g, 95% CI 10 to 46; Indian 31 g, 95% CI 20 to 42; Pakistani 21 g, 95% CI 12 to 29).\n\nCONCLUSIONS: There is no indication that the mean birth weight of South Asian offspring of women born in England and Wales is higher than the mean birth weight of those whose mothers were born in the Indian sub-continent. This suggests a shared physiological tendency for down-regulation of fetal growth transmissible across generations. Within the UK, there is unlikely to be any appreciable increase in mean birth weight of South Asian babies over the next few decades.", "author" : [ { "dropping-particle" : "", "family" : "Leon", "given" : "David A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moser", "given" : "Kath A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of epidemiology and community health", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "6" ] ] }, "page" : "544-51", "title" : "Low birth weight persists in South Asian babies born in England and Wales regardless of maternal country of birth. Slow pace of acculturation, physiological constraint or both? Analysis of routine data.", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0143-005X", "PMID" : "12177085", "abstract" : "OBJECTIVE: To assess differences in birth weight between all first and second generation South Asian babies born in Southampton, and trends since 1957.\n\nDESIGN: Retrospective, cohort study.\n\nSETTING: Birth records for babies born in Southampton from 1957 to 1996 were searched to identify all babies born of South Asian origin (including from the Indian subcontinent, East Africa, and elsewhere).\n\nMAIN OUTCOME MEASURES: All information recorded in the birth record about the mother and baby was extracted.\n\nRESULTS: 2395 full term (>37 weeks; mean birth weight 3110; 95%CI 3092 to 3129) singleton births were identified. Detailed analysis was restricted to mothers either born in the Indian subcontinent (India, Pakistan, or Bangladesh (1435)) or United Kingdom (283). Mean birth weight and % low birth weight (<2500 g) were 3133 g (95%CI 3108 to 3157) and 7.5%, for first generation babies and 3046 g (2992 to 3099) and 11.7% for second generation babies. There was no trend over time to increased average birth weight in either first or second generation babies. Adjusting for other factors that were statistically significantly related to birth weight (gender, gestational age, mother's age, maternal weight at 15 weeks, parity, and mother's ethnic group) did not alter the trends.\n\nCONCLUSIONS: For that group in the UK who derive from the Indian subcontinent, average birth weight is significantly less than the national average. There has not been any increase in the average birth weight over the past 40 years, and the birth weight of babies of women who were born in the UK are no greater. The persistence of lower than desirable birth weight may result long term in higher than average rates of diabetes and heart disease in these groups.", "author" : [ { "dropping-particle" : "", "family" : "Margetts", "given" : "B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohd Yusof", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dallal", "given" : "Z", "non-dropping-particle" : "Al", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "A A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of epidemiology and community health", "id" : "ITEM-5", "issue" : "9", "issued" : { "date-parts" : [ [ "2002", "9" ] ] }, "page" : "684-7", "title" : "Persistence of lower birth weight in second generation South Asian babies born in the United Kingdom.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "17,25,42,43,56", "plainTextFormattedCitation" : "17,25,42,43,56", "previouslyFormattedCitation" : "17,25,42,43,56" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }17,25,42,43,56, advocating for the role of genetic and epigenetic factors as well as gene-environment interactions to explain the observed physiological and epidemiological variation in the risk for metabolic disease and type 2 diabetes.1.2 Aims of this thesisThe overall aim of this thesis is to explore the role of genetic variants and epigenetic differences to explain the greater risk for type 2 diabetes in South Asians. Countless epidemiological studies show that similar to South Asians, many racial / ethnic minorities have a substantially higher risk for cardiovascular and metabolic diseases than do white CaucasiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1047-2797", "PMID" : "8680628", "abstract" : "To identify factors associated with diabetes mellitus and to determine whether racial differences in these factors, especially socioeconomic status, explain the high prevalence of diabetes among African-Americans, we performed a cross-sectional study using a population-based, representative sample from three US communities. The participants comprised 975 white and 418 African-American adults, aged 35 to 54 years. The main outcome variable was the presence of diabetes defined by either self-report or abnormal results on the oral glucose tolerance test (serum glucose level > 10.0 mmol/L (180 mg/dL) 1 hour after 50-g oral glucose dose). Compared to their white counterparts, African-American participants were more overweight, displayed greater central adiposity, and had lower socioeconomic status. Diabetes was over twice as prevalent among African-Americans (10.3%) as compared to whites (4.6%; odds ratio (OR) = 2.38; 95% confidence interval (95% CI): 1.50, 3.75; P = 0.0001). After adjustments for racial differences in age, socioeconomic status, overweight, and central adiposity, African-Americans remained over twice as likely to have diabetes compared to whites (OR = 2.35; 95% CI: 1.49, 3.73; P = 0.0003). The excess prevalence of diabetes in African-Americans was greatest in individuals of low socioeconomic status (OR = 4.09) and least among individuals of high socioeconomic status (OR = 1.90; P < 0.001 for trend). Racial differences in obesity and socioeconomic status do not appear to explain fully the higher prevalence of diabetes among African-Americans. African-American race seems to be a strong, independent risk factor for diabetes, especially among individuals of low socioeconomic status.", "author" : [ { "dropping-particle" : "", "family" : "Brancati", "given" : "F L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whelton", "given" : "P K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuller", "given" : "L H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klag", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of epidemiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1996", "1" ] ] }, "page" : "67-73", "title" : "Diabetes mellitus, race, and socioeconomic status. A population-based study.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/diacare.26.8.2392", "ISSN" : "0149-5992", "abstract" : "OBJECTIVE--To determine racial differences in the prevalence of diabetic nephropathy, cardiovascular disease (CVD), and risk of mortality in a national health care system. RESEARCH DESIGN AND METHODS--A longitudinal cohort study was conducted in 429,918 veterans with diabetes. Racial minority groups were analyzed for baseline differences in prevalence of early diabetic nephropathy, diabetic end-stage renal disease (ESRD) and CVD, and longitudinal risk of mortality compared with Caucasians. RESULTS--The 429,918 patients identified with diabetes were of the following racial groups: Caucasian (56.2%), African American (15.3%), Asian (0.5%), Native American (0.4%), and unknown race (21.4%). Minority individuals were, on average, younger and less likely to have CVD but were more likely to have renal disease than Caucasians. After adjustment for age, sex, and economic status, African Americans (adjusted odds ratio [OR] = 1.3, 95% CI 1.2-1.4) and Native Americans (1.5, 1.1-2.1) were more likely to have early diabetic nephropathy than Caucasians. Diabetic ESRD was more likely to be present in African Americans (1.9, 1.9-2.0), Hispanics (1.4, 1.3-1.4), Asians (1.8, 1.5-2.1), and Native Americans (1.9, 1.5-2.3) than Caucasians. Concurrently, the adjusted OR of CVD in racial minority groups was 27-49% less than in Caucasians, whereas the 18-month risk of mortality among people from most racial minority groups was 7-12% lower than in Caucasians. CONCLUSIONS--We conclude that when access to care is comparable, microvascular complications, macrovascular disease, and subsequent death occur with different frequencies among various racial groups.", "author" : [ { "dropping-particle" : "", "family" : "Young", "given" : "B. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maynard", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boyko", "given" : "E. J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes Care", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2003", "7", "25" ] ] }, "page" : "2392-2399", "title" : "Racial Differences in Diabetic Nephropathy, Cardiovascular Disease, and Mortality in a National Population of Veterans", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0003-4819", "PMID" : "8686981", "abstract" : "PURPOSE: To review the available information on prevalence, complications, and mortality of non-insulin-dependent diabetes mellitus and primary and secondary prevention activities in black persons, Hispanic persons, Native Americans, and Asians and Pacific Islanders in the United States.\n\nDATA SOURCE: MEDLINE search from 1976 to 1994 through the PlusNet search system.\n\nSTUDY SELECTION: Use of the key words non-insulin-dependent diabetes mellitus, the names of each specific minority group, socioeconomic status, acculturation, genetics, diet, complications, mortality, treatment, and intervention (lifestyle or medication) produced 290 unduplicated articles. Additional articles cited in the original articles were also included.\n\nDATA EXTRACTION: Risk factors, incidence, prevalence, complications, and mortality of non-insulin-dependent diabetes mellitus.\n\nDATA SYNTHESIS: All minorities, except natives of Alaska, have a prevalence of non-insulin-dependent diabetes mellitus that is two to six times greater than that of white persons. Most studies show an increased prevalence of nephropathy that can be as much as six times higher than that of white persons. Retinopathy has variably higher rates in black persons, Hispanic persons, and Native Americans. Amputations are done more frequently among black persons than among white persons (9.0 per 1000 compared with 6.3 per 1000), and Pima Indians have 3.7 times more amputations than do white persons. Diabetes-related mortality is higher for minorities than for white persons, and the rate is increasing. The relative importance of genetic heritage, diet, exercise, socioeconomic status, culture, language, and access to health care in the prevalence, incidence, and mortality of diabetes is not clear. Studies of interventions in minority populations are in progress.\n\nCONCLUSION: Diabetes should be treated as a public health problem for minority populations.", "author" : [ { "dropping-particle" : "", "family" : "Carter", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pugh", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monterrosa", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of internal medicine", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "1996", "8", "1" ] ] }, "page" : "221-32", "title" : "Non-insulin-dependent diabetes mellitus in minorities in the United States.", "type" : "article-journal", "volume" : "125" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "58\u201360", "plainTextFormattedCitation" : "58\u201360", "previouslyFormattedCitation" : "58\u201360" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }58–60. Studying ethnic variation using white Caucasians as a comparison can help elucidate disease pathogenesis and uncover differences, be they physiological, genetic, environmental or a combination thereof, that mark a greater risk in certain racial groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1503/cmaj.050649", "ISSN" : "1488-2329", "PMID" : "16389231", "author" : [ { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waltman", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006", "1", "3" ] ] }, "page" : "25-6", "title" : "Why don't pigs get diabetes? Explanations for variations in diabetes susceptibility in human populations living in a diabetogenic environment.", "type" : "article-journal", "volume" : "174" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "61", "plainTextFormattedCitation" : "61", "previouslyFormattedCitation" : "61" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }61. The thesis is comprised of three parts. In Chapter two, we evaluate genetic susceptibility to type 2 diabetes among South Asians and white Caucasians using existing published literature. There is much speculation in the literature that the higher prevalence of type 2 diabetes results from a greater genetic predisposition among South Asians10,11, either because of higher risk conferred by SNPs or increased frequency of risk alleles. This hypothesis was evaluated first by conducting a meta-analysis of the literature to create a robust list of SNPs predisposing to type 2 diabetes. Next, we compared the risk estimates from this list between South Asians and white Caucasians. We also assessed population burden from these SNPs in both ethnic groups. The last part of the chapter tested eight novel SNPs discovered from South Asian studies in a cohort of 69,033 white Caucasians. In Chapter three, we explore whether a greater risk for type 2 diabetes in South Asians is influenced by a genetic predisposition to beta-cell dysfunction and if this is magnified in the presence of abdominal adiposity. To do this, we constructed a genotype score of polymorphisms robustly linked to beta-cell dysfunction with evidence from GWA-studies, functional studies, animal models, and/or monogenic diabetes models. We evaluate whether the impact of these SNPs is greater in those with abdominal obesity. We then contrasted findings in South Asians with those from white Caucasians in 5,302 people from the EpiDREAM cohortADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc12-2553", "ISSN" : "1935-5548", "PMID" : "23603917", "abstract" : "OBJECTIVE: To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.\n\nRESEARCH DESIGN AND METHODS: In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.\n\nRESULTS: Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).\n\nCONCLUSIONS: T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Changchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xiaohe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Jackie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keavney", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudet", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "2836-42", "title" : "Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "62" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62.As differences in body composition between South Asians and whites are present at birth, the variation may in part be a result of differences in the in-utero environment. Methylation of genes is the most commonly studied epigenetic mark and results from interactions between the environment and the genetic make-up of an individual. Therefore, Chapter four evaluates genetic and epigenetic differences in birth weight and length between the two ethnic groups using data from two Canadian birth cohortsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2458-13-79", "ISSN" : "1471-2458", "PMID" : "23356884", "abstract" : "BACKGROUND: People who originate from the Indian subcontinent (South Asians) suffer among the highest rates of type 2 diabetes in the world. Prior evidence suggests that metabolic risk factors develop early in life and are influenced by maternal and paternal behaviors, the intrauterine environment, and genetic factors. The South Asian Birth Cohort Study (START) will investigate the environmental and genetic basis of adiposity among 750 South Asian offspring recruited from highly divergent environments, namely, rural and urban India and urban Canada.\n\nMETHODS: Detailed information on health behaviors including diet and physical activity, and blood samples for metabolic parameters and DNA are collected from pregnant women of South Asian ancestry who are free of significant chronic disease. They also undergo a provocative test to diagnose impaired glucose tolerance and gestational diabetes. At delivery, cord blood and newborn anthropometric indices (i.e. birth weight, length, head circumference and skin fold thickness) are collected. The mother and growing offspring are followed prospectively and information on the growth trajectory, adiposity and health behaviors will be collected annually up to age 3 years. Our aim is to recruit a minimum of 750 mother-infant pairs equally divided between three divergent environments: rural India, urban India, and Canada.\n\nSUMMARY: The START cohort will increase our understanding of the environmental and genetic determinants of adiposity and related metabolic abnormalities among South Asians living in India and Canada.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vasudevan", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Milan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurpad", "given" : "Anura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Koon K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinivasan", "given" : "Krishnamachari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC public health", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "79", "title" : "Rationale and design of South Asian Birth Cohort (START): a Canada-India collaborative study.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "63", "plainTextFormattedCitation" : "63", "previouslyFormattedCitation" : "63" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }63.1.3 Potential impactFindings from this thesis will: (1) further elucidate the etiology and pathogenesis of type 2 diabetes and guide research for diseases with a genetic component, (2) promote an accurate understanding of the differences in risk between South Asians and white Caucasians, and allow for more astute risk stratification in clinical settings, (3) identify genetic and epigenetic targets for the development of novel anti-diabetic drugs, and (4) lastly, allow for recommendations for women during pregnancy based on the epigenetic causes of LBW.Chapter 2*Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white Caucasian populations?*Nota bene: This chapter has been published in: Sohani ZN, Deng WQ, Pare G, Meyre D, Gerstein HC, Anand SS. Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations? Diabetologia. 2014. doi:10.1007/s00125-014-3354-1.Authors’ contributions: ZNS made substantial contributions to the design of the study, acquisition of data, conducting the analysis, the interpretation of the data and drafting the article, and provided final approval of the version to be published. SSA made substantial contributions to conception and design and analysis and interpretation of data, critically revised the article for important intellectual content and provided final approval of the version to be published. WQD contributed to the acquisition of data, critically reviewed the article for important intellectual content and provided final approval of the version to be published. GP, DM and HCG substantially contributed to conception and design, critically revised the draft for important intellectual content and provided final approval of the version to be published. SSA is the guarantor of this work.2.1 BackgroundThe elevated risk for type 2 diabetes among South Asians has been hypothesized to result from a greater genetic predispositionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0971-5916", "PMID" : "17496355", "abstract" : "Genes play an important role in the development of diabetes mellitus. Type 2 diabetes is a polygenic disorder with multiple genes located on different chromosomes contributing to its susceptibility. Analysis of the genetic factors is further complicated by the fact that numerous environmental factors interact with genes to produce the disorder. Only a minority of cases of type 2 diabetes are caused by single gene defects and one example is maturity onset diabetes of the young (MODY). Till date knowledge of the genetics of type 2 diabetes is limited. Consistent with the complex web of physiologic defects in type 2 diabetes, the genetics of the disorder involves a large number of susceptibility genes, each with a relatively small effect. In this article, the studies on genetics of diabetes in Asian Indians are reviewed. As Asian Indians have an increased susceptibility to diabetes and have increased insulin resistance, they are a unique population for carrying out genetic studies. There appears to be certain genes which predispose Indians to diabetes while other genes (for example Pro 12 Ala polymorphism of PPAR gamma gene) which afford protection against diabetes and insulin resistance to Caucasians, do not appear to protect Indians. Further studies are needed to unravel the genetics of diabetes in South Asians .", "author" : [ { "dropping-particle" : "", "family" : "Radha", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Indian journal of medical research", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "3" ] ] }, "page" : "259-74", "title" : "Genetic predisposition to type 2 diabetes among Asian Indians.", "type" : "article-journal", "volume" : "125" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1089/met.2009.0062", "ISSN" : "1557-8518", "PMID" : "19943798", "abstract" : "BACKGROUND: Individuals from South Asia have high diabetes prevalence despite low body weight. We compared the prevalence of diabetes among South Asian Indians with other U.S. ethnic groups and explored correlates of diabetes.\n\nMETHODS: This was a cross-sectional study of 150 South Asian Indians (ages 45-79) in California, using similar methods to the Multi-Ethnic Study of Atherosclerosis (MESA). Type 2 diabetes was classified by fasting plasma glucose (FPG) >or=126 mg/dL, 2-h postchallenge glucose >or=200 mg/dL, or use of hypoglycemic medication.\n\nRESULTS: A total of 29% of Asian Indians had diabetes, 37% had prediabetes, and 34% had normal glucose tolerance. After full adjustment for covariates, Indians still had significantly higher odds of diabetes compared to whites and Latinos, but not significantly different from African Americans and Chinese Americans in MESA: Indians [odds ratio (OR), 1.0], whites [OR, 0.29; 95% confidence interval (CI), 0.17-0.49], Latinos (OR, 0.59; CI, 0.34-1.00) African Americans (OR, 0.77; CI 0.45-1.32), Chinese Americans (OR, 0.78, CI, 0.45-1.32). Variables associated with prediabetes or diabetes among Indians included hypertension, fatty liver, visceral adiposity, microalbuminuria, carotid intima media thickness, and stronger traditional Indian beliefs.\n\nCONCLUSIONS: Indian immigrants may be more likely to have diabetes than other U.S. ethnic groups, and cultural factors may play a role, suggesting that this is a promising area of research.", "author" : [ { "dropping-particle" : "", "family" : "Kanaya", "given" : "A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wassel", "given" : "C L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stewart", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herrington", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budoff", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ranpura", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolic syndrome and related disorders", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "157-64", "title" : "Prevalence and correlates of diabetes in South asian indians in the United States: findings from the metabolic syndrome and atherosclerosis in South asians living in america study and the multi-ethnic study of atherosclerosis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "64,65", "plainTextFormattedCitation" : "64,65", "previouslyFormattedCitation" : "64,65" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }64,65, either because of larger risk estimates for each single nucleotide polymorphism or increased frequency of risk alleles. This hypothesis has not been systematically evaluated. The purpose of this systematic review is to: (1) establish risk estimates for SNPs predisposing South Asians to type 2 diabetes; (2) compare risk estimates, risk alleles and risk allele frequencies (RAFs) of type 2 diabetes predisposing SNPs between South Asians and white Caucasians; and (3) explore the association of novel SNPs discovered from South Asians in a large cohort of white Caucasians.2.2 Methods2.2.1 Systematic review of studies assessing genetic risk of type 2 diabetes in South AsiansSearch strategy and selection criteria: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane registry (from inception to 17 June 2013; MEDLINE and Embase searched using OvidSP) were searched for studies of genetic variants associated with type 2 diabetes in South Asians. South Asians were defined as individuals originating from India, Pakistan, Bangladesh or Sri Lanka. The search strategy was developed in consultation with a research librarian and did not restrict by type of genetic variant, language of study or study design. The full search strategy is presented in Supplementary Table 2.1. Experts were consulted, and reference lists of included articles and relevant excluded articles were searched. Two reviewers (ZNS and WQD) independently assessed each study for eligibility based on four questions: (1) is at least one study population South Asian; (2) is type 2 diabetes the outcome studied; (3) is the exposure a genetic variant; and (4) is this a genetic association study? Disagreements were independently resolved by a third reviewer (SSA). Articles that passed the screening phase were reviewed in depth.Full-text review and data extraction: Conference abstracts, narrative reviews and other systematic reviews were excluded after full-text review. Primary studies investigating genetic variants other than bi-allelic SNPs (e.g. insertions, deletions, length polymorphisms, haplotypes and complex tri-allelic SNPs) or with fewer than 25 cases were excluded. These limitations were implemented to ensure that estimates from included studies could be pooled and were of sound quality. Additionally, to ensure robustness of our results, SNPs from included studies carried forward to meta-analysis were limited to those that previously reached genome-wide significance (P<5x10-8) in any ethnicity. If datasets were published more than once, publication with the largest sample size or the one recommended by the senior author was used for meta-analysis. Two reviewers conducted a full-text assessment and extracted data on participant characteristics (sample size, age, BMI, fasting glucose, waist and hip circumferences, and % men), study design (study methods, region) and results (SNP, risk allele, RAF in cases and controls, and risk estimate with a 95% CI). For GWA-studies in South Asians, SNPs associated with type 2 diabetes at P<103 were considered for meta-analysis.Quality assessment of included studies: Using recommendations from the STrengthening the REporting of Genetic Association Studies (STREGA) guidelinesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pmed.1000022", "ISSN" : "1549-1676", "PMID" : "19192942", "abstract" : "Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.", "author" : [ { "dropping-particle" : "", "family" : "Little", "given" : "Julian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Higgins", "given" : "Julian P T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ioannidis", "given" : "John P A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moher", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gagnon", "given" : "France", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elm", "given" : "Erik", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khoury", "given" : "Muin J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cohen", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davey-Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grimshaw", "given" : "Jeremy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwinn", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williamson", "given" : "Robin E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zou", "given" : "Guang Yong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hutchings", "given" : "Kim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Candice Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tait", "given" : "Valerie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiens", "given" : "Miriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golding", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McLaughlin", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paterson", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wells", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fortier", "given" : "Isabel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zecevic", "given" : "Maja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "King", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Infante-Rivard", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stewart", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birkett", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "2", "3" ] ] }, "page" : "e22", "publisher" : "Public Library of Science", "title" : "STrengthening the REporting of Genetic Association Studies (STREGA): an extension of the STROBE statement.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "66", "plainTextFormattedCitation" : "66", "previouslyFormattedCitation" : "66" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }66, the following three components were considered for quality assessment: testing for Hardy–Weinberg equilibrium (HWE) in controlsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1101/068163", "ISSN" : "1559-6095", "PMID" : "22383645", "abstract" : "Genetic association studies are used to find candidate genes or genome regions that contribute to a specific disease by testing for a correlation between disease status and genetic variation. This article provides a broad outline of the design and analysis of such studies, focusing on case-control studies in candidate genes or regions.", "author" : [ { "dropping-particle" : "", "family" : "Lewis", "given" : "Cathryn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Jo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cold Spring Harbor protocols", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "3" ] ] }, "page" : "297-306", "title" : "Introduction to genetic association studies.", "type" : "article-journal", "volume" : "2012" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "67", "plainTextFormattedCitation" : "67", "previouslyFormattedCitation" : "67" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }67, reporting of genotyping call rate or appraisal of genotyping quality by duplication, and sources of case and control ascertainment.Statistical analysis: Agreement between reviewers was reported with Cohen’s κ statistic. Allelic ORs were calculated using RAFs and sample size for cases and controls and assessed for significance using Fisher’s exact test. The ORs were not adjusted for any covariates. ORs for SNPs in linkage disequilibrium (LD) (r2>0.8) obtained from independent cohorts were meta-analysed using random effects model weighted by inverse variance. As data on LD in South Asians was not available using the SNAP software (Broad Institute, Cambridge, MA)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/bioinformatics/btn564", "ISSN" : "1367-4811", "PMID" : "18974171", "abstract" : "SUMMARY: The interpretation of genome-wide association results is confounded by linkage disequilibrium between nearby alleles. We have developed a flexible bioinformatics query tool for single-nucleotide polymorphisms (SNPs) to identify and to annotate nearby SNPs in linkage disequilibrium (proxies) based on HapMap. By offering functionality to generate graphical plots for these data, the SNAP server will facilitate interpretation and comparison of genome-wide association study results, and the design of fine-mapping experiments (by delineating genomic regions harboring associated variants and their proxies). AVAILABILITY: SNAP server is available at .", "author" : [ { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Handsaker", "given" : "Robert E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pulit", "given" : "Sara L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nizzari", "given" : "Marcia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Donnell", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" } ], "container-title" : "Bioinformatics (Oxford, England)", "id" : "ITEM-1", "issue" : "24", "issued" : { "date-parts" : [ [ "2008", "12", "15" ] ] }, "page" : "2938-9", "title" : "SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "68", "plainTextFormattedCitation" : "68", "previouslyFormattedCitation" : "68" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }68, LD was estimated using 1000 Genome (Pilot 1) Centre d'Etude du Polymorphisme (CEU) (Utah residents with northern and western European ancestry). A two-sided α level of 0.05 was considered significant. For a list of SNPs in LD, see Supplementary Table 2.2. Summary RAFs are presented as averages, weighted by sample size, of all included reports. Heterogeneity was estimated using I2 statistic, which indicates the proportion of total variation in estimates attributed to heterogeneity, as well as the Q statisticADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/1082-989X.11.2.193", "ISSN" : "1082-989X", "PMID" : "16784338", "abstract" : "In meta-analysis, the usual way of assessing whether a set of single studies is homogeneous is by means of the Q test. However, the Q test only informs meta-analysts about the presence versus the absence of heterogeneity, but it does not report on the extent of such heterogeneity. Recently, the I(2) index has been proposed to quantify the degree of heterogeneity in a meta-analysis. In this article, the performances of the Q test and the confidence interval around the I(2) index are compared by means of a Monte Carlo simulation. The results show the utility of the I(2) index as a complement to the Q test, although it has the same problems of power with a small number of studies.", "author" : [ { "dropping-particle" : "", "family" : "Huedo-Medina", "given" : "Tania B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00e1nchez-Meca", "given" : "Julio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mar\u00edn-Mart\u00ednez", "given" : "Fulgencio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Botella", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological methods", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "6" ] ] }, "page" : "193-206", "title" : "Assessing heterogeneity in meta-analysis: Q statistic or I2 index?", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "69", "plainTextFormattedCitation" : "69", "previouslyFormattedCitation" : "69" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }69. A cut-off of 25% for I2 was used to represent minimal heterogeneity, 50% to represent moderate and 75% to represent high heterogeneity. Quanto, Los Angeles, CA (version 1.2.4) was used for sample size and power calculations assuming a disease prevalence of 10% and an additive model of inheritance. All other statistical analyses were conducted in R (version 3.0.2).2.2.2 Comparison of meta-analysed SNPs in South Asians with white CaucasiansEstimates for SNPs associated with type 2 diabetes in this meta-analysis were retrieved for white Caucasians from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. Specific details on the consortium have been previously describedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2383", "ISSN" : "1546-1718", "PMID" : "22885922", "abstract" : "To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teslovich", "given" : "Tanya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segr\u00e8", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Hassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Hyun Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esko", "given" : "Tonu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraser", "given" : "Ross M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Ashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller-Nurasyid", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pechlivanis", "given" : "Sonali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiltshire", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Loic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinnunen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossin", "given" : "Elizabeth J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vedantam", "given" : "Sailaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen Hong L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer", "given" : "Krista", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontanillas", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmen", "given" : "Oddgeir L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunt", "given" : "Sarah E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl G P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sivapalaratnam", "given" : "Suthesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stan\u010d\u00e1kov\u00e1", "given" : "Alena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tikkanen", "given" : "Emmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carey", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crenshaw", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorkhan", "given" : "Mozhgan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edkins", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eury", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsen", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gertow", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hreidarsson", "given" : "Astradur B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kravic", "given" : "Jasmina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krjut\u0161kov", "given" : "Kaarel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langford", "given" : "Cordelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leander", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindholm", "given" : "Eero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4nnist\u00f6", "given" : "Satu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mirza", "given" : "Ghazala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fchleisen", "given" : "Thomas W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musk", "given" : "Bill", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkin", "given" : "Melissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rallidis", "given" : "Loukianos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saramies", "given" : "Jouko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigur\u00f0sson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinbach", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trakalo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veglia", "given" : "Fabrizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wennauer", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winckler", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabaneh", "given" : "Delilah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trip", "given" : "Mieke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "N\u00f6then", "given" : "Markus M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilsgaard", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hovingh", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Jackie F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nj\u00f8lstad", "given" : "Inger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korpi-Hy\u00f6v\u00e4lti", "given" : "Eeva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saltevo", "given" : "Juha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metspalu", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldassarre", "given" : "Damiano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tremoli", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erbel", "given" : "Raimund", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f6ckel", "given" : "Karl-Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moebus", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donnelly", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "page" : "981-90", "title" : "Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "70", "plainTextFormattedCitation" : "70", "previouslyFormattedCitation" : "70" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }70. Briefly, DIAGRAM stage 1 is a publicly available database of 12 GWAS studies with 12,171 cases and 56,862 controls. DIAGRAM authors tested SNPs with minor allele frequency >1% for association with type 2 diabetes under an additive model. The authors combined summary estimates from the 12 GWAS using fixed-effect inverse-variance-weighted meta-analysis.Effect sizes from white Caucasians in DIAGRAM and South Asians from this meta-analysis were transformed to natural logs and compared using a Z test. RAFs in white Caucasians were acquired from published GWAS (gwastudies/). Additionally, a genotype score of SNPs present in both groups was constructed to compare population burden from these SNPs. The genotype score was constructed as below:Genotype score = Σ [loge (ORi) × RAFi]Variance for the genotype score was estimated as:Variance = Σ {RAFi2 × variance[loge (ORi)]}Genotype scores from both ethnicities were compared using a Z test.2.2.3 Testing novel SNPs discovered from South Asians GWA-studies in white CaucasiansFour GWAS have been conducted in South AsiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2337/db12-1077", "ISSN" : "1939-327X", "PMID" : "23300278", "abstract" : "We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10\u207b\u00b3) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10\u207b\u2074) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 \u00d7 10\u207b\u2078) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10\u207b\u00b3) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10\u207b\u2074) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10\u207b\u2075 to < 10\u207b\u2077), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garavito", "given" : "Martha L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjonnes", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Weang Kee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yasushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirose", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jai Rup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "M Ilyas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maegawa", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobe", "given" : "Kazuyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "page" : "1746-55", "title" : "Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1371/journal.pgen.1001363", "ISSN" : "1553-7404", "PMID" : "21490949", "abstract" : "Recent large genome-wide association studies (GWAS) have identified multiple loci which harbor genetic variants associated with type 2 diabetes mellitus (T2D), many of which encode proteins not previously suspected to be involved in the pathogenesis of T2D. Most GWAS for T2D have focused on populations of European descent, and GWAS conducted in other populations with different ancestry offer a unique opportunity to study the genetic architecture of T2D. We performed genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945 controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians (977 cases, 1,169 controls). In addition to the search for novel variants implicated in T2D, these multi-ethnic cohorts serve to assess the transferability and relevance of the previous findings from European descent populations in the three major ethnic populations of Asia, comprising half of the world's population. Of the SNPs associated with T2D in previous GWAS, only variants at CDKAL1 and HHEX/IDE/KIF11 showed the strongest association with T2D in the meta-analysis including all three ethnic groups. However, consistent direction of effect was observed for many of the other SNPs in our study and in those carried out in European populations. Close examination of the associations at both the CDKAL1 and HHEX/IDE/KIF11 loci provided some evidence of locus and allelic heterogeneity in relation to the associations with T2D. We also detected variation in linkage disequilibrium between populations for most of these loci that have been previously identified. These factors, combined with limited statistical power, may contribute to the failure to detect associations across populations of diverse ethnicity. These findings highlight the value of surveying across diverse racial/ethnic groups towards the fine-mapping efforts for the casual variants and also of the search for variants, which may be population-specific.", "author" : [ { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Rick Twee-Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan-Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik-Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E-Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "editor" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Greg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "4" ] ] }, "page" : "e1001363", "publisher" : "Public Library of Science", "title" : "Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71\u201374", "plainTextFormattedCitation" : "71\u201374", "previouslyFormattedCitation" : "71\u201374" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71–74, which collectively identified nine SNPs (P<5×108). All studies used a case–control design. Associations with type 2 diabetes for eight of the nine SNPs have not been independently discovered from GWAS in any other ethnicity. We compared the association for these eight novel SNPs with type 2 diabetes in white Caucasians from DIAGRAM. An overview of the study design is presented in Figure 2.1.Figure 2. SEQ Figure \* ARABIC 1 Overview of the study designFigure SEQ Figure \* ARABIC 2.2 Flow diagram of the systematic review of South Asian literature investigating genetic variants predisposing to type 2 diabetes 2.3 Results2.3.1 Systematic review and meta-analysisSearch yields: A total of 3,898 articles were originally screened, of which 170 were carried to full-text review. Ninety-four studies met the inclusion and exclusion criteria, and 38 studies comprising 31 independent cohorts contained data on SNPs with evidence of genome-wide significance in any ethnicity. These 38 studies were included in the systematic review. Figure 2.2 depicts the selection process and lists reasons for exclusion at each stage. There was excellent agreement on study inclusion between reviewers (unweighted κ =0.898).Study characteristics: All included studies were in English and published in 2004 or later. Most large datasets (>2,500 people) were published after 2008. Eight of the 31 cohorts were from North India, four from South India, five from Pakistan, one from the Eastern region (Orissa), four from Indians residing in Singapore, two from Sri Lanka, one from Indians residing in Trinidad, one from Indians residing in Mauritius and one from all over the South Asian subcontinent; four were unspecified.Participant characteristics: Studies eligible for analysis included 29,618 cases and 40,329 controls. Controls were described as healthy individuals who were normoglycaemic and/or non-diabetic. Men accounted for 54% of cases and 53% of controls. Age ranged from 34 to 62 years in casesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0973-7138", "PMID" : "19805902", "abstract" : "Studies on the association of the Pro12Ala and C1431T polymorphisms of PPAR? with diabetes and obesity have revealed extensive population-dependent variations. However, association of these polymorphisms with the metabolic syndrome and its individual components has not been well investigated in the Indian population. The Indian population harbours the maximum number of diabetics in the world who are thus more susceptible to metabolic disorders. We screened a South Indian population (N=699) for a possible association of these polymorphisms with the metabolic syndrome (MS) and type 2 diabetes. We also investigated the correlation of these two single-nucleotide polymorphisms (SNPs) with plasma resistin levels. The C1431T SNP was associated with higher levels of plasma resistin (P=0.017). Furthermore, C1431T was associated with resistin in different tertiles. Prevalence of the 'Pro-C' haplotype decreased with increasing tertiles of resistin (84.1% to 75.4%, P=0.037). Plasma resistin levels were not found to be associated with MS and type 2 diabetes. These results point to a likely association of plasma resistin levels with PPAR? polymorphisms in the Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Haseeb", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iliyas", "given" : "Mohammad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Subhabrata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqui", "given" : "Arif A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naik", "given" : "Sudhir R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Sudip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suragani", "given" : "Madhuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehtesham", "given" : "Nasreen Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of biosciences", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "405-14", "title" : "Single-nucleotide polymorphisms in peroxisome proliferator-activated receptor gamma and their association with plasma levels of resistin and the metabolic syndrome in a South Indian population.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1399-0004.2010.01577.x", "ISSN" : "1399-0004", "PMID" : "21062274", "abstract" : "Variants in hepatocyte nuclear factor 4A (HNF4A) cause maturity onset diabetes of the young (MODY 1). The objective of the study was to screen the coding and the promoter regions of HNF4A mutations in 87 unrelated South Indian subjects with clinically diagnosed MODY with severe forms of diabetes referred to a tertiary diabetes centre. In addition, we looked at the association of common polymorphisms in HNF4 A gene in subjects with MODY (n = 199), early onset type 2 diabetes (T2DM) (n = 505), late onset T2DM (n = 287) and normal glucose tolerance (NGT) (n = 247). We identified three novel mutations in the P2 promoter region of HNF4A, namely -1009 G/C, -129 T/C and -79 C/T. Co-segregation with diabetes was noted with the -1009 G/C and -129 T/C in one MODY family. We also studied eight single nucleotide polymorphisms (SNPs) of HNF4A gene. The frequency of the minor allele of the rs2144908 was significantly higher in subjects with MODY (p < 0.01) and that of rs736823 was significantly higher in early onset T2DM (p = 0.001). Minor allele frequency of rs1884614 and rs2071197 was significantly lower in early onset T2DM when compared to NGT subjects (p < 0.01). Minor allele frequency of Val255Met was significantly lower in MODY, early onset T2DM and late onset T2DM compared to NGT subjects (p < 0.01). This is the first report of MODY 1 mutations from India and shows that 3.4% of clinically diagnosed MODY subjects have MODY 1. In addition, we report SNPs of HNF4A that are both susceptible to, and protective against, MODY and early onset T2DM.", "author" : [ { "dropping-particle" : "", "family" : "Anuradha", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical genetics", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "541-9", "title" : "Association of novel variants in the hepatocyte nuclear factor 4A gene with maturity onset diabetes of the young and early onset type 2 diabetes.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "75,76", "plainTextFormattedCitation" : "75,76", "previouslyFormattedCitation" : "75,76" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }75,76, and from 28 to 62 years in controlsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-006-0502-2", "ISSN" : "0012-186X", "PMID" : "17093941", "abstract" : "AIMS AND HYPOTHESIS: India has the greatest number of diabetic subjects in any one country, but the genetic basis of type 2 diabetes mellitus in India is poorly understood. Common non-coding variants in the transcription factor 7-like 2 gene (TCF7L2) have recently been strongly associated with increased risk of type 2 diabetes in European populations. We investigated whether TCF7L2 variants are also associated with type 2 diabetes mellitus in the Indian population.\n\nMATERIALS AND METHODS: We genotyped type 2 diabetes patients (n = 955) and ethnically matched control subjects (n = 399) by sequencing three single nucleotide polymorphisms (SNPs) (rs7903146, rs12255372 and rs4506565) in TCF7L2.\n\nRESULTS: We observed a strong association with all the polymorphisms, including rs12255372 (odds ratio [OR] 1.50 [95% CI = 1.24-1.82], p = 4.0 x 10(-5)), rs4506565 (OR 1.48 [95% CI = 1.24-1.77], p = 2.0 x 10(-5)) and rs7903146 (OR 1.46 [95% CI = 1.22-1.75], p = 3.0 x 10(-5)). All three variants showed increased relative risk when homozygous rather than heterozygous, with the strongest risk for rs12255372 (OR 2.28 [95% CI = 1.40-3.72] vs OR 1.43 [95% CI = 1.11-1.83]). We found no association of the TCF7L2 genotypes with age at diagnosis, BMI or WHR, but the risk genotype at rs12255372 was associated with higher fasting plasma glucose (p = 0.001), higher 2-h plasma glucose (p = 0.0002) and higher homeostasis model assessment of insulin resistance (HOMA-R; p = 0.012) in non-diabetic subjects.\n\nCONCLUSIONS: Our study in Indian subjects replicates the strong association of TCF7L2 variants with type 2 diabetes in other populations. It also provides evidence that variations in TCF7L2 may play a crucial role in the pathogenesis of type 2 diabetes by influencing both insulin secretion and insulin resistance. TCF7L2 is an important gene for determining susceptibility to type 2 diabetes mellitus and it transgresses the boundaries of ethnicity.", "author" : [ { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohankrishna", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "A T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "1" ] ] }, "page" : "63-7", "title" : "Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0973-7138", "PMID" : "19805902", "abstract" : "Studies on the association of the Pro12Ala and C1431T polymorphisms of PPAR? with diabetes and obesity have revealed extensive population-dependent variations. However, association of these polymorphisms with the metabolic syndrome and its individual components has not been well investigated in the Indian population. The Indian population harbours the maximum number of diabetics in the world who are thus more susceptible to metabolic disorders. We screened a South Indian population (N=699) for a possible association of these polymorphisms with the metabolic syndrome (MS) and type 2 diabetes. We also investigated the correlation of these two single-nucleotide polymorphisms (SNPs) with plasma resistin levels. The C1431T SNP was associated with higher levels of plasma resistin (P=0.017). Furthermore, C1431T was associated with resistin in different tertiles. Prevalence of the 'Pro-C' haplotype decreased with increasing tertiles of resistin (84.1% to 75.4%, P=0.037). Plasma resistin levels were not found to be associated with MS and type 2 diabetes. These results point to a likely association of plasma resistin levels with PPAR? polymorphisms in the Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Haseeb", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iliyas", "given" : "Mohammad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Subhabrata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqui", "given" : "Arif A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naik", "given" : "Sudhir R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Sudip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suragani", "given" : "Madhuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehtesham", "given" : "Nasreen Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of biosciences", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "405-14", "title" : "Single-nucleotide polymorphisms in peroxisome proliferator-activated receptor gamma and their association with plasma levels of resistin and the metabolic syndrome in a South Indian population.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "75,77", "plainTextFormattedCitation" : "75,77", "previouslyFormattedCitation" : "75,77" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }75,77. BMI was reported for cases and controls in 79% of studies and ranged from 25.0 to 31.9 kg/m2 in casesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2010.04.024", "ISSN" : "1532-8600", "PMID" : "20580033", "abstract" : "Recent genomewide association studies have identified several new gene variants associated with type 2 diabetes mellitus (T2D) mostly in European populations. These need to be replicated in other populations. We studied 926 unrelated T2D and 812 normal glucose-tolerant subjects randomly selected from the Chennai Urban Rural Epidemiology Study in Southern India. A total of 45 single nucleotide polymorphisms (SNPs) from 15 genes and 13 unannotated loci identified from recent genomewide association T2D studies were genotyped. Only 6 of 45 SNPs studied were replicated in this South Indian population. Three SNPs-rs7756992 (P = .007), rs7754840 (P = .015), and rs6931514 (P = .029)-of the CDKAL1, rs7020996 (P = .003) of the CDKN2A/B gene, rs7923837 (P = .038) of the HHEX gene, and rs12056034 (P = .033) of the BAZ1B gene were associated with T2D in our population. Large-scale studies are needed in our population to validate our findings.", "author" : [ { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2010", "12" ] ] }, "page" : "1760-6", "title" : "Replication of recently described type 2 diabetes gene variants in a South Indian population.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.4238/vol9-4gmr883", "ISSN" : "1676-5680", "PMID" : "20967696", "abstract" : "A population-based study was undertaken to evaluate linkage between single-nucleotide polymorphisms known as risk factors and type 2 diabetes in an Indian population. The study population was comprised of 40 normal glucose-tolerant individuals (21 males and 19 females) and 40 type 2 diabetes patients (21 males and 19 females). The genes and their corresponding single-nucleotide polymorphisms that we screened were VDR (rs 731236 and rs 1544410), IL-6 (rs 1800795), TCF7L2 (rs 7903146) and TNF-\u03b1 (rs 1800629). The risk alleles were more frequent in the subjects with type 2 diabetes, except for the TNF-\u03b1 gene, which was very infrequent in the population; the normal allele occurred at high and similar frequencies in both normal and diabetic individuals.", "author" : [ { "dropping-particle" : "", "family" : "Mukhopadhyaya", "given" : "P N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Acharya", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavan", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purohit", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutha", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics and molecular research : GMR", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "2060-8", "title" : "Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in an Indian population.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "78,79", "plainTextFormattedCitation" : "78,79", "previouslyFormattedCitation" : "78,79" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }78,79 and from 19.4 to 28.1 kg/m2 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1464-5491.2011.03438.x", "ISSN" : "1464-5491", "PMID" : "21913964", "abstract" : "AIMS: Recent genome-wide association studies have identified several Type 2 diabetes-related loci. We investigated the effect of susceptibility genetic variants, individually, together and in combination with conventional risk factors, on Type 2 diabetes and diabetes-related traits in Indians.\n\nMETHODS: We genotyped 33 variants in 1808 Indian patients and 1549 control subjects and performed association analyses with Type 2 diabetes and related traits using an additive model for individual variant and for genetic risk score based on 32 polymorphisms. The discriminatory value of genetic risk over conventional risk factors was analysed using receiver-operating characteristics curve analysis.\n\nRESULTS: The allelic odds ratio ranged from 1.01 (95% CI 0.85-1.19) to 1.66 (95% CI 1.32-2.01) for single-variant analyses. Although, only 16 variants had significant odds ratios, the direction of association for others was similar to earlier reports. The odds ratio for Type 2 diabetes at each genetic risk score point was 1.11 (95% CI 1.09-1.14; P = 5.6 \u00d7 10(-17)) and individuals with extremes of genetic risk score (\u2265 29.0 and \u2264 17.0) had a 7.5-fold difference in risk of Type 2 diabetes. The discrimination rate between control subjects and patients improved marginally on addition of genetic risk score to conventional risk factors (area under curve = 0.959 and 0.963, respectively; P = 0.001). Of all the quantitative traits analysed, MC4R variants showed strong association with BMI (P = 4.1 \u00d7 10(-4)), fat mass per cent (P = 2.4 \u00d7 10(-4)) and other obesity-related traits, including waist circumference and hip circumference (P = 2.0 \u00d7 10(-3) for both), as well as insulin resistance (P =0.02).\n\nCONCLUSIONS: We replicated the association of well-established common variants with Type 2 diabetes in Indians and observed a similar association as reported in Western populations. Combined analysis of 32 variants aids identification of subgroups at increased risk of Type 2 diabetes, but adds only a minor advantage over conventional risk factors.", "author" : [ { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "M V K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinay", "given" : "D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandeep", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aruna", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Joglekar", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Priyadharshini", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maheshwari", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "121-7", "title" : "Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of Type 2 diabetes and related traits in Indians.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00125-011-2063-2", "ISSN" : "1432-0428", "PMID" : "21350842", "abstract" : "AIMS/HYPOTHESIS: Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODS: Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur.\n\nRESULTS: SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 \u00d7 10(-12)), BMI (p = 2.25 \u00d7 10(-4)) and age at onset of diabetes (p = 0.002).\n\nCONCLUSIONS/INTERPRETATION: We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "1368-74", "title" : "Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80,81", "plainTextFormattedCitation" : "80,81", "previouslyFormattedCitation" : "80,81" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80,81 in controls. A majority of studies reported fasting glucose: 58% in cases (ranging from 6.41 to 10.60 mmol/l)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0060212", "ISSN" : "1932-6203", "PMID" : "23577093", "abstract" : "We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established.", "author" : [ { "dropping-particle" : "", "family" : "Uma Jyothi", "given" : "Kommoju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jayaraj", "given" : "Maruda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subburaj", "given" : "Kadarkarai Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Kotla Jaya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumuda", "given" : "Irgam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakshmi", "given" : "Velaga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Battini Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "e60212", "title" : "Association of TCF7L2 gene polymorphisms with T2DM in the population of Hyderabad, India.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1464-5491.2011.03257.x", "ISSN" : "1464-5491", "PMID" : "21294771", "abstract" : "AIMS: A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians.\n\nMETHODS: We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged \u226540 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies.\n\nRESULTS: In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95%CI 0.24-0.67) kg/m(2) per A-allele (P=3.0 \u00d7 10(-5) ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P=0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95%CI) 1.18 (1.07-1.30); P=0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95%CI 1.14-1.31); P=1.07 \u00d7 10(-8) ] even after adjusting for BMI [1.18 (95%CI 1.10-1.27); P=1.02 \u00d7 10(-5) ] or waist circumference [1.18 (95%CI 1.10-1.27); P=3.97 \u00d7 10(-5) ].\n\nCONCLUSIONS: The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaudhary", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellary", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashmi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "673-80", "title" : "An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference.", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "82,83", "plainTextFormattedCitation" : "82,83", "previouslyFormattedCitation" : "82,83" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82,83 and 63% in controls (ranging from 4.60 to 6.89 mmol/l)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2007.04.012", "ISSN" : "0026-0495", "PMID" : "17697858", "abstract" : "One thousand thirty-eight normal glucose-tolerant and 1031 type 2 diabetic subjects selected from the Chennai Urban Rural Epidemiology Study were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay to investigate the association of rs12255372(G/T) and rs7903146(C/T) polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene with type 2 diabetes mellitus in Asian Indians. The frequency of the \"T\" allele of both rs12255372(G/T) and rs7903146(C/T) polymorphisms was significantly higher in diabetic subjects (23% and 33%) compared to that in normal glucose-tolerant subjects (19% and 28%; P = .001 and P = .0001, respectively). Logistic regression analysis of the rs12255372(G/T) polymorphism showed that the odds ratio (adjusted for age, sex, and body mass index) was 1.56 (95% confidence interval [CI], 1.03-2.37; P = .034) for the TT genotype and 1.29 (95% CI, 1.06-1.58; P = .011) for the TG genotype when compared with the GG genotype. Adjusted odds ratios for the TT and TC genotypes of the rs7903146(C/T) polymorphism were found to be 1.50 (95% CI, 1.08-2.08; P = .013) and 1.44 (95% CI, 1.18-1.76; P = .0003), respectively, compared with the CC genotype. Normal glucose-tolerant subjects with the TT genotype of rs12255372(G/T) had significantly higher 2-hour plasma glucose levels (mean +/- SD, 6.1 +/- 1.4 mmol/L) than those with the GG genotype (5.6 +/- 1.0 mmol/L, P = .011). Normal glucose-tolerant subjects with the TT genotype of rs7903146(C/T) polymorphism had significantly higher 2-hour plasma glucose levels (mean +/- SD, 6.0 +/- 1.3 mmol/L) than those with the CC genotype (5.6 +/- 1.0 mmol/L, P = .004). In conclusion, the T allele of the rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene confer susceptibility to type 2 diabetes mellitus in Asian Indians.", "author" : [ { "dropping-particle" : "", "family" : "Bodhini", "given" : "Dhanasekaran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhar", "given" : "Monalisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narayani", "given" : "Nagarajan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "1174-8", "title" : "The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71,84", "plainTextFormattedCitation" : "71,84", "previouslyFormattedCitation" : "71,84" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71,84. Very few datasets reported additional clinical information; 29% reported waist circumference in cases and controls. Only three studies reported hip circumference. Supplementary Table 2.3 provides a summary of all included studies.Quality assessment: Agreement with HWE in controls, genotyping call rate, and source of controls and cases for included studies are summarised in Supplementary Table 2.4. One study did not report compliance with HWEADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gene.2012.09.072", "ISSN" : "1879-0038", "PMID" : "23036708", "abstract" : "BACKGROUND: Type 2 diabetes mellitus is a multifactorial and polygenic disease, which is considered as a major life threatening problem all over the world. There has been a worldwide effort in the identification of susceptibility genes for type 2 diabetes mellitus and its complications. At present, adequate data is not available dealing with MTHFR (rs1801133) and PPAR\u03b32 (rs1801282) gene polymorphisms and its association with type 2 diabetes mellitus cases among north Indian populations. Thus, we conceived the need for further studies to investigate MTHFR and PPAR\u03b32 gene polymorphisms and their susceptibility to type 2 diabetes mellitus in north Indian population.\n\nMATERIALS AND METHODS: In this study, a total 175 subjects including 87 type 2 diabetes mellitus cases and 88 controls were enrolled. MTHFR and PPAR\u03b32 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).\n\nRESULTS: The MTHFR gene CC, CT, TT genotype frequencies obtained were 40%, 43%, and 17% in type 2 diabetes mellitus cases and 56%, 29%, and 15% in healthy controls respectively. The OR for CC was 0.54 (95%CI 0.29-0.98, P=0.041, \u03c7(2)=4.18, power=0.98), for CT 1.76 (95%CI 0.94-3.30, P=0.07, \u03c7(2)=3.2, power=0.96), and for TT 1.2 (95%CI 0.53-2.70, P=0.66, \u03c7(2)=0.198, power=0.76). The PPAR\u03b32 gene GG CG, CC genotype frequencies obtained were 28%, 41%, and 31% in cases and 40%, 39%, and 21% in healthy controls respectively. OR for GG was 0.58 (95%CI 0.30-1.09, P=0.08, \u03c7(2)=2.9, power=0.96), for CG 1.12 (95%CI 0.61-2.05, P=0.71, \u03c7(2)=0.137, power=0.778), and for CC 1.63 (95%CI 0.82-3.23, P=0.156, \u03c7(2)=2.01, power=0.92).\n\nCONCLUSION: It might be recommended that MTHFR CC genotype seems to be a good marker for the early identification of population at risk of type 2 diabetes mellitus. While we have detected significant difference in allelic frequencies of PPAR\u03b32 C (Proline) and G (Alanine), but at genotypic level significant difference was not detected in this case-control study. Further study with larger groups may be required to validate the study.", "author" : [ { "dropping-particle" : "", "family" : "Raza", "given" : "Syed Tasleem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbas", "given" : "Shania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahmed", "given" : "Faisal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fatima", "given" : "Jalees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaidi", "given" : "Zeashan Haider", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahdi", "given" : "Farzana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gene", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "12", "15" ] ] }, "page" : "375-9", "title" : "Association of MTHFR and PPAR\u03b32 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population.", "type" : "article-journal", "volume" : "511" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "85", "plainTextFormattedCitation" : "85", "previouslyFormattedCitation" : "85" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }85. P-value thresholds for HWE varied by study (range: P=10-2 to 10-4). SNPs in one study deviated from HWEADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2009-0688", "ISSN" : "1945-7197", "PMID" : "19892838", "abstract" : "CONTEXT: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized.\n\nOBJECTIVE: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. Design: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians.\n\nRESULTS: In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.\n\nCONCLUSIONS: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.", "author" : [ { "dropping-particle" : "", "family" : "Tan", "given" : "Jonathan T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel P K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nurbaya", "given" : "Siti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Xiu Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leong", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seet", "given" : "Lin Tze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siew", "given" : "Wei Fong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kon", "given" : "Winston", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saw", "given" : "Seang Mei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jeannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chew", "given" : "Suok Kai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "390-7", "title" : "Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore.", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "86", "plainTextFormattedCitation" : "86", "previouslyFormattedCitation" : "86" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86; rs2237892 and rs2237897 deviated from HWE at P=0.002 and P=0.001, respectively. The SNPs were excluded from analysis because the HWE threshold in the primary report was fairly conservative. Six (16%) studies did not appraise genotyping qualityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gene.2012.09.072", "ISSN" : "1879-0038", "PMID" : "23036708", "abstract" : "BACKGROUND: Type 2 diabetes mellitus is a multifactorial and polygenic disease, which is considered as a major life threatening problem all over the world. There has been a worldwide effort in the identification of susceptibility genes for type 2 diabetes mellitus and its complications. At present, adequate data is not available dealing with MTHFR (rs1801133) and PPAR\u03b32 (rs1801282) gene polymorphisms and its association with type 2 diabetes mellitus cases among north Indian populations. Thus, we conceived the need for further studies to investigate MTHFR and PPAR\u03b32 gene polymorphisms and their susceptibility to type 2 diabetes mellitus in north Indian population.\n\nMATERIALS AND METHODS: In this study, a total 175 subjects including 87 type 2 diabetes mellitus cases and 88 controls were enrolled. MTHFR and PPAR\u03b32 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).\n\nRESULTS: The MTHFR gene CC, CT, TT genotype frequencies obtained were 40%, 43%, and 17% in type 2 diabetes mellitus cases and 56%, 29%, and 15% in healthy controls respectively. The OR for CC was 0.54 (95%CI 0.29-0.98, P=0.041, \u03c7(2)=4.18, power=0.98), for CT 1.76 (95%CI 0.94-3.30, P=0.07, \u03c7(2)=3.2, power=0.96), and for TT 1.2 (95%CI 0.53-2.70, P=0.66, \u03c7(2)=0.198, power=0.76). The PPAR\u03b32 gene GG CG, CC genotype frequencies obtained were 28%, 41%, and 31% in cases and 40%, 39%, and 21% in healthy controls respectively. OR for GG was 0.58 (95%CI 0.30-1.09, P=0.08, \u03c7(2)=2.9, power=0.96), for CG 1.12 (95%CI 0.61-2.05, P=0.71, \u03c7(2)=0.137, power=0.778), and for CC 1.63 (95%CI 0.82-3.23, P=0.156, \u03c7(2)=2.01, power=0.92).\n\nCONCLUSION: It might be recommended that MTHFR CC genotype seems to be a good marker for the early identification of population at risk of type 2 diabetes mellitus. While we have detected significant difference in allelic frequencies of PPAR\u03b32 C (Proline) and G (Alanine), but at genotypic level significant difference was not detected in this case-control study. Further study with larger groups may be required to validate the study.", "author" : [ { "dropping-particle" : "", "family" : "Raza", "given" : "Syed Tasleem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbas", "given" : "Shania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahmed", "given" : "Faisal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fatima", "given" : "Jalees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaidi", "given" : "Zeashan Haider", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahdi", "given" : "Farzana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gene", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "12", "15" ] ] }, "page" : "375-9", "title" : "Association of MTHFR and PPAR\u03b32 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population.", "type" : "article-journal", "volume" : "511" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0946-2716", "PMID" : "17665514", "abstract" : "Common variants of TCF7L2, encoding a beta-cell-expressed transcription factor, are strongly associated with increased risk of type 2 diabetes (T2D). We examined this association using both prospective and case-control designs. A total of 2,676 healthy European white middle-aged men from the prospective NPHSII (158 developed T2D over 15 years surveillance) were genotyped for two intronic SNPs [rs 7903146 (IVS3C>T) and rs12255372 (IVS4G>T)] which showed strong linkage disequilibrium (D' = 0.88, p<0.001; R(2)=0.76, p<0.001). The IVS5T allele frequency was 0.28 (95% CI 0.27-0.29) and 0.33 (0.28-0.39) in healthy and T2D, respectively (p=0.04). Compared to CC men, CT and TT men had an adjusted [for age, body mass index, systolic blood pressure, triglyceride and C-reactive protein levels] hazard ratio for T2D of 1.65 (1.13-2.41) and 1.87 (0.99-3.53), respectively, p<0.01. The population attributable fraction for diabetes risk was 17%. In 1459, European white T2D men and women (60% male), T allele frequency was 0.36 (0.34-0.38), and compared to NPHSII healthy men the OR for T2D for the CT and TT subjects was 1.43 (1.24-1.65) and 2.11 (1.69-2.63), respectively p=<0.0001. A similar effect was observed in 919 T2D Indian Asians [OR=1.50 (1.14-1.99) and 1.64 (1.03-2.63) p=0.003] and 385 Afro-Caribbean subjects [OR=1.25 (0.90-1.75) and 1.32 (0.74-2.33) p=0.17] compared to non-diabetic ethnically matched subjects from South London. Weaker associations were found for the IVS4G>T in all studies. Linkage disequilibrium between the two SNPs was high in Indian Asians (D'=0.94), but much weaker in Afro-Caribbeans (D'=0.17) and haplotype frequencies differed markedly in this group. These results extend previous observations to other ethnic groups, and strongly confirm that TCF7L2 genotype is a major risk factor for development of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gable", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Jackie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ireland", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stephens", "given" : "Jeffrey W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hurel", "given" : "Steven J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Ka Wah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmen", "given" : "Jutta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappuccio", "given" : "Francesco P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elkeles", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godsland", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "George J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talmud", "given" : "Philippa J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of molecular medicine (Berlin, Germany)", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2006", "12" ] ] }, "page" : "1005-14", "title" : "Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women.", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2337/diacare.2951046", "ISSN" : "0149-5992", "PMID" : "16644635", "abstract" : "OBJECTIVE: To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians.\n\nRESEARCH DESIGN AND METHODS: South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects.\n\nRESULTS: The Caucasian diabetic subjects had significantly lower prevalence of PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas.\n\nCONCLUSIONS: Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.", "author" : [ { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vimaleswaran", "given" : "Karani S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babu", "given" : "Hunsur Narayan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abate", "given" : "Nicola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandalia", "given" : "Manisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Satija", "given" : "Pankaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Majumder", "given" : "Partha P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deepa", "given" : "Raj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Sathyanarayana M R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "1046-51", "title" : "Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0043-3144", "PMID" : "22512215", "abstract" : "OBJECTIVE: To examine the effect of genetic variation in KCNJ11 on the risk of Type 2 diabetes mellitus in Trinidadians.\n\nMETHODS: The coding and bordering intron-exon regions of the KCNJ11 gene were sequenced in 168 diabetic and 61 non-diabetic subjects who historically were thought to be of South Asian Indian ancestry as well as 66 diabetic and 59 non-diabetic subjects of African ancestry. Allele and haplotype frequency differences were calculated between cases and controls and linkage equilibrium was assessed across the KCNJ11 region.\n\nRESULTS: We identified novel missense mutations in both subject groups including A94P and R369C in a diabetic Indo-Trinidadian subject, S113G in a non-diabetic Indo-Trinidadian subject, and S118L in a diabetic Afro-Trinidadian subject. It is unknown if these mutations are pathogenic as other family members were not available for study. Additionally, the common variant E23K was associated with Type 2 diabetes in the Indo-Trinidadian group (OR = 1.797 [1.148-2.814], p = 0.0098).\n\nCONCLUSIONS: Rare variants in KCNJ11 are segregating in the Indo- and Afro-Trinidadian populations and further studies are needed to determine their contribution, if any, to the overall prevalence of diabetes in these groups. Common variants such as E23K may increase the risk in the Indo-Trinidadian population.", "author" : [ { "dropping-particle" : "", "family" : "Boodram", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyake", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayes", "given" : "M G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "G I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cockburn", "given" : "B N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The West Indian medical journal", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "604-7", "title" : "Association of the KCNJ11 variant E23K with type 2 diabetes in Indo-Trinidadians.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1007/s00125-008-1186-6", "ISSN" : "1432-0428", "PMID" : "19005641", "abstract" : "AIMS AND HYPOTHESIS: Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune.\n\nMETHODS: We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India.\n\nRESULTS: We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13-1.40; p = 3 x 10(-5)). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01-0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09-0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06-1.37; p = 4.0 x 10(-3)), and also for waist circumference and other anthropometric variables.\n\nCONCLUSIONS: Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mani", "given" : "K R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kale", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshpande", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Krishnaveni", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veena", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fall", "given" : "C H D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "M I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "A T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "2" ] ] }, "page" : "247-52", "title" : "FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1111/j.1469-1809.2010.00580.x", "ISSN" : "1469-1809", "PMID" : "20597906", "abstract" : "The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18-clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan-based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p-value = 0.00191; p-value = 0.00179, respectively), and odds ratios of 2.1 (dominant-model) and 2.0 (recessive-model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist-Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single-SNP, combined-SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally-learned sedentary lifestyle and fat-enriched dietary habits, WHR rather than body-mass-index emerged as a robust predictor of risk for T2D in this population.", "author" : [ { "dropping-particle" : "", "family" : "Gupta", "given" : "Vipin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khadgawat", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Hon Keung Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Satish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Ajay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Vadlamudi Raghavendra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sachdeva", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of human genetics", "id" : "ITEM-6", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "361-8", "title" : "A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India.", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "85,87\u201391", "plainTextFormattedCitation" : "85,87\u201391", "previouslyFormattedCitation" : "85,87\u201391" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }85,87–91. Furthermore, three studies had a genotyping call rate below 95% for all reported SNPsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2009-0688", "ISSN" : "1945-7197", "PMID" : "19892838", "abstract" : "CONTEXT: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized.\n\nOBJECTIVE: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. Design: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians.\n\nRESULTS: In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.\n\nCONCLUSIONS: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.", "author" : [ { "dropping-particle" : "", "family" : "Tan", "given" : "Jonathan T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel P K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nurbaya", "given" : "Siti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Xiu Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leong", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seet", "given" : "Lin Tze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siew", "given" : "Wei Fong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kon", "given" : "Winston", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saw", "given" : "Seang Mei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jeannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chew", "given" : "Suok Kai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "390-7", "title" : "Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore.", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db09-1386", "ISSN" : "1939-327X", "PMID" : "20424228", "abstract" : "OBJECTIVE: Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control studies.\n\nRESEARCH DESIGN AND METHODS: We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects.\n\nRESULTS: We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 x 10(-3) to 4.6 x 10(-34)). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71-2.09], P = 4.6 x 10(-34)). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of beta-cell function (P = 6.9 x 10(-8) and 3 x 10(-4), respectively), which looked consistent with recessive and under-dominant models, respectively.\n\nCONCLUSIONS: Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.", "author" : [ { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spurgeon", "given" : "Charles J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "Seema", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "Smita R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "M V Kranthi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "Swami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "Chittaranjan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "Giriraj R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2010", "8" ] ] }, "page" : "2068-74", "title" : "Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/jhg.2011.87", "ISSN" : "1435-232X", "PMID" : "21814223", "abstract" : "Common variants of fat mass and obesity-associated gene (FTO, fat mass- and obesity-associated gene) have been shown to be associated with obesity and type 2 diabetes in population of European and non-European ethnicity. However, studies in Indian population have provided inconsistent results. Here, we examined association of eight FTO variants (rs1421085, rs8050136, rs9939609, rs9930506, rs1861867, rs9926180, rs2540769 and rs708277) with obesity and type 2 diabetes in 5364 North Indians (2474 type 2 diabetes patients and 2890 non-diabetic controls) in two stages. None of the variants including previously reported intron 1 variants (rs1421085, rs8050136, rs9939609 and rs9930506) showed body mass index (BMI)-dependent/independent association with type 2 diabetes. However, rs1421085, rs8050136 and rs9939609 were associated with obesity status and measures of obesity (BMI, waist circumference and waist-to-hip ratio) in stage 2 and combined study population. Meta-analysis of the two study population results also revealed that rs1421085, rs8050136 and rs9939609 were significantly associated with BMI both under the random- and fixed-effect models (P (random/fixed)=0.02/0.0001, 0.004/0.0006 and 0.01/0.01, respectively). In conclusion, common variants of FTO were associated with obesity, but not with type 2 diabetes in North Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahendran", "given" : "Yuvaraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nigam", "given" : "Shubhanchi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubey", "given" : "Himanshu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Binuja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of human genetics", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "720-6", "publisher" : "The Japan Society of Human Genetics", "title" : "Common variants of FTO and the risk of obesity and type 2 diabetes in Indians.", "title-short" : "J Hum Genet", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "86,92,93", "plainTextFormattedCitation" : "86,92,93", "previouslyFormattedCitation" : "86,92,93" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86,92,93.Risk estimates for SNPs associated with type 2 diabetes in South Asians: Thirty SNPs with previous evidence of genome-wide significance in other ethnicities were available for meta-analysis. Pooled estimates were significant for 15 of the 30 SNPs (Figure 2.3). Summary ORs, on the whole, suggested between a 1.15- and a 1.35-fold increase in susceptibility for type 2 diabetes per risk allele. Surprisingly, the risk alleles for both KCNQ1 polymorphisms substantially increased the odds of type 2 diabetes (rs2237892 OR 1.62, 95% CI 1.01-2.59; rs2237897 OR 2.19, 95% CI 1.25-3.82). High degrees of between-study heterogeneity were evident for CDKAL1 rs7754840 (I2=70%, Q=19.99, p<0.01) and TCF7L2 rs7903146 (I2=90%, Q=99.52, P <0.01). In the TCF7L2 meta-analysis, there was some evidence that larger studies had more conservative estimates, although Chauhan et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-1386", "ISSN" : "1939-327X", "PMID" : "20424228", "abstract" : "OBJECTIVE: Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control studies.\n\nRESEARCH DESIGN AND METHODS: We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects.\n\nRESULTS: We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 x 10(-3) to 4.6 x 10(-34)). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71-2.09], P = 4.6 x 10(-34)). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of beta-cell function (P = 6.9 x 10(-8) and 3 x 10(-4), respectively), which looked consistent with recessive and under-dominant models, respectively.\n\nCONCLUSIONS: Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.", "author" : [ { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spurgeon", "given" : "Charles J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "Seema", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "Smita R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "M V Kranthi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "Swami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "Chittaranjan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "Giriraj R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2010", "8" ] ] }, "page" : "2068-74", "title" : "Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "92", "plainTextFormattedCitation" : "92", "previouslyFormattedCitation" : "92" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }92 and Uma Jyothi et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0060212", "ISSN" : "1932-6203", "PMID" : "23577093", "abstract" : "We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established.", "author" : [ { "dropping-particle" : "", "family" : "Uma Jyothi", "given" : "Kommoju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jayaraj", "given" : "Maruda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subburaj", "given" : "Kadarkarai Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Kotla Jaya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumuda", "given" : "Irgam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakshmi", "given" : "Velaga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Battini Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "e60212", "title" : "Association of TCF7L2 gene polymorphisms with T2DM in the population of Hyderabad, India.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "82", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "82" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82 were exceptions. The smallest study (n=40 case/control pairs) depicted an association that was directionally inconsistent with the othersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4238/vol9-4gmr883", "ISSN" : "1676-5680", "PMID" : "20967696", "abstract" : "A population-based study was undertaken to evaluate linkage between single-nucleotide polymorphisms known as risk factors and type 2 diabetes in an Indian population. The study population was comprised of 40 normal glucose-tolerant individuals (21 males and 19 females) and 40 type 2 diabetes patients (21 males and 19 females). The genes and their corresponding single-nucleotide polymorphisms that we screened were VDR (rs 731236 and rs 1544410), IL-6 (rs 1800795), TCF7L2 (rs 7903146) and TNF-\u03b1 (rs 1800629). The risk alleles were more frequent in the subjects with type 2 diabetes, except for the TNF-\u03b1 gene, which was very infrequent in the population; the normal allele occurred at high and similar frequencies in both normal and diabetic individuals.", "author" : [ { "dropping-particle" : "", "family" : "Mukhopadhyaya", "given" : "P N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Acharya", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavan", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purohit", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutha", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics and molecular research : GMR", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "2060-8", "title" : "Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in an Indian population.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "79", "plainTextFormattedCitation" : "79", "previouslyFormattedCitation" : "79" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }79. Heterogeneity estimates did not change much without this outlier (I2=90%, Q=90.31, P<0.01). Additional sources of heterogeneity could include consanguinityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-1809.2010.00580.x", "ISSN" : "1469-1809", "PMID" : "20597906", "abstract" : "The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18-clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan-based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p-value = 0.00191; p-value = 0.00179, respectively), and odds ratios of 2.1 (dominant-model) and 2.0 (recessive-model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist-Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single-SNP, combined-SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally-learned sedentary lifestyle and fat-enriched dietary habits, WHR rather than body-mass-index emerged as a robust predictor of risk for T2D in this population.", "author" : [ { "dropping-particle" : "", "family" : "Gupta", "given" : "Vipin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khadgawat", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Hon Keung Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Satish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Ajay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Vadlamudi Raghavendra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sachdeva", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of human genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "361-8", "title" : "A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India.", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/1471-2350-9-59", "ISSN" : "1471-2350", "PMID" : "18598350", "abstract" : "BACKGROUND: Recent genome-wide association (GWA) studies have identified several unsuspected genes associated with type 2 diabetes (T2D) with previously unknown functions. In this investigation, we have examined the role of 9 most significant SNPs reported in GWA studies: [peroxisome proliferator-activated receptor gamma 2 (PPARG2; rs 1801282); insulin-like growth factor two binding protein 2 (IGF2BP2; rs 4402960); cyclin-dependent kinase 5, a regulatory subunit-associated protein1-like 1 (CDK5; rs7754840); a zinc transporter and member of solute carrier family 30 (SLC30A8; rs13266634); a variant found near cyclin-dependent kinase inhibitor 2A (CDKN2A; rs10811661); hematopoietically expressed homeobox (HHEX; rs 1111875); transcription factor-7-like 2 (TCF7L2; rs 10885409); potassium inwardly rectifying channel subfamily J member 11(KCNJ11; rs 5219); and fat mass obesity-associated gene (FTO; rs 9939609)].\n\nMETHODS: We genotyped these SNPs in a case-control sample of 918 individuals consisting of 532 T2D cases and 386 normal glucose tolerant (NGT) subjects of an Asian Sikh community from North India. We tested the association between T2D and each SNP using unconditional logistic regression before and after adjusting for age, gender, and other covariates. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels using multiple linear regression analysis.\n\nRESULTS: Four of the nine SNPs revealed a significant association with T2D; PPARG2 (Pro12Ala) [odds ratio (OR) 0.12; 95% confidence interval (CI) (0.03-0.52); p = 0.005], IGF2BP2 [OR 1.37; 95% CI (1.04-1.82); p = 0.027], TCF7L2 [OR 1.64; 95% CI (1.20-2.24); p = 0.001] and FTO [OR 1.46; 95% CI (1.11-1.93); p = 0.007] after adjusting for age, sex and BMI. Multiple linear regression analysis revealed significant association of two of nine investigated loci with diabetes-related quantitative traits. The 'C' (risk) allele of CDK5 (rs 7754840) was significantly associated with decreased HDL-cholesterol levels in both NGT (p = 0.005) and combined (NGT and T2D) (0.005) groups. The less common 'C' (risk) allele of TCF7L2 (rs 10885409) was associated with increased LDL-cholesterol (p = 0.010) in NGT and total and LDL-cholesterol levels (p = 0.008; p = 0.003, respectively) in combined cohort.\n\nCONCLUSION: To our knowledge, this is first study reporting the role of some recently emerged loci with T2D in a high risk population of As\u2026", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Shizhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jairup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrell", "given" : "Robert E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nath", "given" : "Swapan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "Mohammed I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "59", "title" : "Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "91,94", "plainTextFormattedCitation" : "91,94", "previouslyFormattedCitation" : "91,94" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }91,94. One very obvious outlier existed in the meta-analysis for CDKAL1 (OR 2.22, 95% CI 1.64-2.98)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2350-9-59", "ISSN" : "1471-2350", "PMID" : "18598350", "abstract" : "BACKGROUND: Recent genome-wide association (GWA) studies have identified several unsuspected genes associated with type 2 diabetes (T2D) with previously unknown functions. In this investigation, we have examined the role of 9 most significant SNPs reported in GWA studies: [peroxisome proliferator-activated receptor gamma 2 (PPARG2; rs 1801282); insulin-like growth factor two binding protein 2 (IGF2BP2; rs 4402960); cyclin-dependent kinase 5, a regulatory subunit-associated protein1-like 1 (CDK5; rs7754840); a zinc transporter and member of solute carrier family 30 (SLC30A8; rs13266634); a variant found near cyclin-dependent kinase inhibitor 2A (CDKN2A; rs10811661); hematopoietically expressed homeobox (HHEX; rs 1111875); transcription factor-7-like 2 (TCF7L2; rs 10885409); potassium inwardly rectifying channel subfamily J member 11(KCNJ11; rs 5219); and fat mass obesity-associated gene (FTO; rs 9939609)].\n\nMETHODS: We genotyped these SNPs in a case-control sample of 918 individuals consisting of 532 T2D cases and 386 normal glucose tolerant (NGT) subjects of an Asian Sikh community from North India. We tested the association between T2D and each SNP using unconditional logistic regression before and after adjusting for age, gender, and other covariates. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels using multiple linear regression analysis.\n\nRESULTS: Four of the nine SNPs revealed a significant association with T2D; PPARG2 (Pro12Ala) [odds ratio (OR) 0.12; 95% confidence interval (CI) (0.03-0.52); p = 0.005], IGF2BP2 [OR 1.37; 95% CI (1.04-1.82); p = 0.027], TCF7L2 [OR 1.64; 95% CI (1.20-2.24); p = 0.001] and FTO [OR 1.46; 95% CI (1.11-1.93); p = 0.007] after adjusting for age, sex and BMI. Multiple linear regression analysis revealed significant association of two of nine investigated loci with diabetes-related quantitative traits. The 'C' (risk) allele of CDK5 (rs 7754840) was significantly associated with decreased HDL-cholesterol levels in both NGT (p = 0.005) and combined (NGT and T2D) (0.005) groups. The less common 'C' (risk) allele of TCF7L2 (rs 10885409) was associated with increased LDL-cholesterol (p = 0.010) in NGT and total and LDL-cholesterol levels (p = 0.008; p = 0.003, respectively) in combined cohort.\n\nCONCLUSION: To our knowledge, this is first study reporting the role of some recently emerged loci with T2D in a high risk population of As\u2026", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Shizhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jairup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrell", "given" : "Robert E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nath", "given" : "Swapan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "Mohammed I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "59", "title" : "Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "94", "plainTextFormattedCitation" : "94", "previouslyFormattedCitation" : "94" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94. Heterogeneity estimates without this outlier diminished substantially (I2=0%, Q=2.80, P=0.73). None of the outliers was excluded from our final analysis. A majority of genes associated with type 2 diabetes from this meta-analysis (ADCY5, CDKAL1, CDKN2A/B, HHEX, IGF2BP2, SLC30A8, TCF7L2 and KCNQ1) are involved in pancreatic beta cell function, while two are implicated in insulin sensitivity (PPARG) and adiposity (FTO). This is not surprising as insulin secretion is a more heritable trait than insulin actionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s001250050046", "ISSN" : "0012-186X", "PMID" : "10768089", "abstract" : "AIMS/HYPOTHESIS: To estimate the heritability of insulin sensitivity and insulin secretion, both of which are considered to contribute to the development of Type II (non-insulin-dependent) diabetes mellitus.\n\nMETHODS: Intraclass correlation coefficients and heritability estimates for insulin sensitivity (euglycaemic clamp) as well as first-phase and late-phase insulin secretion (intravenous glucose tolerance test) were calculated in 21 monozygotic and 20 dizygotic twin pairs of the same sex between 54 and 72 years of age.\n\nRESULTS: Intrapair correlations for all traits were consistently higher in monozygotic than in dizygotic pairs. Insulin secretion correlated significantly only between monozygotic (first-phase r = 0.55; p = 0.003 and late-phase r = 0.66; p < 0.001) twins giving heritability estimates of 0.55 and 0.58, respectively. Insulin-stimulated glucose uptake showed a more modest correlation between monozygotic twins (r = 0.46; p = 0.015). The heritability estimate was 0.37. The heritability estimate for waist-to-hip ratio was 0.76 in female and 0.70 in male twins.\n\nCONCLUSION/INTERPRETATION: Genetic variability seems to contribute to the variance of insulin sensitivity as well as of insulin secretion. In the current study, genetic variance accounted almost 60% for the variance in glucose-stimulated insulin secretion and almost 40% for the variance in insulin-stimulated glucose uptake. Our data is also compatible with findings in monogenic forms of diabetes in which genetic defects in insulin secretion play a predominant part in the pathogenesis of hyperglycaemia.", "author" : [ { "dropping-particle" : "", "family" : "Lehtovirta", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsblom", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2000", "3" ] ] }, "page" : "285-93", "title" : "Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "95", "plainTextFormattedCitation" : "95", "previouslyFormattedCitation" : "95" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }95. In addition to the above, eight novel SNPs were identified from South-Asian-only GWAS; these are discussed later in this paper.2.3.2 Comparison of effect sizes, RAF, and risk alleles between South Asians and white CaucasiansMeta-analysis estimates in South Asians were compared with white Caucasians from DIAGRAM; no significant differences were identified for most SNPs (P<0.05) (Figure 2.3), although two SNPs showed heterogeneity (KCNQ1 rs2237897 and IGF2BP2 rs4402960). South Asians had a slightly smaller OR for IGF2BP2 rs4402960 (South Asians: 1.07, 95% CI 1.04?1.09; white Caucasians: 1.13, 95% CI 1.09?1.17). Figure 2.4 presents a Venn diagram of overlapping type 2 diabetes predisposing genes in South Asians and white Caucasians, as well as genes unique to both groups. Variation in RAFs between South Asians and white Caucasians was observed, but no consistent trend was evident; South Asians did not consistently have an RAF greater than white Caucasians (Figure 2.4). While the risk allele for HHEX was the same in both ethnicities, the RAF differed; the risk allele is the minor allele in South Asians, but the major/common allele in whites. Risk alleles for six SNPs (SLC30A8 rs13266634, ADCY5 rs11708067, PPARG rs1801282, CHCHD9 (also known as also known as CHCHD2P9) rs13292136, KCNQ1 rs2237897 and CDKN2A/B rs10811661) were major/common alleles in both ethnicities.Figure 2. SEQ Figure \* ARABIC 3 Forest plot of SNPs associated with type 2 diabetes in South Asians from systematic review and white Caucasians from DIAGRAM. Chr: Chromosome; RAF: risk allele frequency; P het: P-value for heterogeneity. SNPs are ordered by level of significance in South Asian meta-analysis.Figure 2. SEQ Figure \* ARABIC 4 Venn diagram of SNPs common to South Asians and white Caucasians and SNPs unique to both groups. CENTD2 is also known as ARAP1; TMEM195 is also known as AGMO. The green box includes genes with GWAS evidence for association with type 2 diabetes; the pink box includes genes with GWAS evidence in whites and association with type 2 diabetes in this meta-analysis; and yellow with genes identified from a trans-ethnic meta-analysis of South Asians and white Caucasians.2.3.3 Testing novel SNPs discovered from South Asian GWA-studies in white CaucasiansThe systematic review included four GWAS in South Asians, which identified nine SNPs associated with type 2 diabetes at genome-wide significance. With the exception of HMG20A rs7178572 (South Asian OR: 1.09, 95% CI 1.06-1.12; white Caucasian OR: 1.08, 95% CI 1.05-1.10)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pgen.1002741", "ISSN" : "1553-7404", "PMID" : "22693455", "abstract" : "Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m\u00b2) compared to obese cases (BMI\u226530 Kg/m\u00b2). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m\u00b2) or 4,123 obese cases (BMI\u226530 kg/m\u00b2), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P\u200a=\u200a8.4\u00d710\u207b\u2079, OR\u200a=\u200a1.13 [95% CI 1.09-1.18]), and this association was stronger than that in obese cases (P\u200a=\u200a0.04, OR\u200a=\u200a1.03 [95% CI 1.00-1.06]). A variant in HMG20A--previously identified in South Asians but not Europeans--was associated with type 2 diabetes in obese cases (P\u200a=\u200a1.3\u00d710\u207b\u2078, OR\u200a=\u200a1.11 [95% CI 1.07-1.15]), although this association was not significantly stronger than that in lean cases (P\u200a=\u200a0.02, OR\u200a=\u200a1.09 [95% CI 1.02-1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P\u200a=\u200a0.0002). In the lean analysis, we observed a weighted per-risk allele OR\u200a=\u200a1.13 [95% CI 1.10-1.17], P\u200a=\u200a3.2\u00d710\u207b\u00b9\u2074. This was larger than the same model fitted in the obese analysis where the OR\u200a=\u200a1.06 [95% CI 1.05-1.08], P\u200a=\u200a2.2\u00d710\u207b\u00b9\u2076. This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amin", "given" : "Najaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ganser", "given" : "Martha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arking", "given" : "Dan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Green", "given" : "Todd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kottgen", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labrune", "given" : "Yann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petersen", "given" : "Ann-Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurdsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vivequin", "given" : "Sidonie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altschuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "page" : "e1002741", "title" : "Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71,96", "plainTextFormattedCitation" : "71,96", "previouslyFormattedCitation" : "71,96" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71,96, the remaining eight SNPs have not been discovered in any other ethnic group. Five of the eight (GRB14 rs3923113, VPS26A rs1082295, HNF4α [also known as HNF4A] rs4812829, ST6GAL1 rs16861329, and AP3S2 rs2028299) were independently replicated in South AsiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72. We tested the eight novel SNPs for association with type 2 diabetes in DIAGRAM. SGCG rs9552911 was monomorphic in white Caucasians. The remaining SNPs were directionally consistent with South Asian estimates and three (AP3S2 rs2028299, GRB14 rs3923113 and HNF4α rs4812829) were nominally (P<0.05) associated with type 2 diabetes (Table 2.1) in DIAGRAM. The other four were not associated with type 2 diabetes in white Caucasians. It should be noted that after meta-analysis of the novel SNPs in South Asians, C6orf57 rs1048886 and GRB14 rs3923113 were slightly above the genome-wide threshold. Lastly, no consistent trend in RAFs was observed. The risk allele for TMEM163 rs6723108 is the same in both ethnicities, but the RAF differs. Specifically, the risk allele is the minor allele in white Caucasians, but the major/common allele in South Asians.Table 2. SEQ Table_2. \* ARABIC 1 Comparison of SNPs discovered from South Asian GWA-studies with white Caucasian estimates from the DIAGRAM ConsortiumChr.GeneSNPRisk allelePheterogeneitySouth AsianWhite CaucasianReferenceSample size (case/control)RAFOR (95% CI)Meta-analysed OR (95% CI)aRAFbDIAGRAM OR (95% CI)Sample size (case/control)13SGCGrs9552911GSaxena et al, 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1077", "ISSN" : "1939-327X", "PMID" : "23300278", "abstract" : "We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10\u207b\u00b3) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10\u207b\u2074) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 \u00d7 10\u207b\u2078) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10\u207b\u00b3) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10\u207b\u2074) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10\u207b\u2075 to < 10\u207b\u2077), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garavito", "given" : "Martha L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjonnes", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Weang Kee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yasushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirose", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jai Rup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "M Ilyas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maegawa", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobe", "given" : "Kazuyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "page" : "1746-55", "title" : "Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "73", "plainTextFormattedCitation" : "73", "previouslyFormattedCitation" : "73" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }732620/42840.081.49 (1.30-1.72)1.49 (1.30-1.72)(p=4.25×10–8)––––15AP3S2rs2028299CKooner et al, 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7118731/398560.311.10 (1.07-1.13)1.10 (1.07-1.13)(p=2.49×10–11)0.261.04 (1.00-1.09)(p=0.03)9580/538100.03Tabassum et al, 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }721256/12090.301.10 (0.96-1.25)3ST6GAL1rs16861329CKooner et, 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7118731/398560.751.09 (1.06-1.12)1.09 (1.06-1.12)(p=1.94×10–9)0.871.03 (0.97-1.09)(p=0.39)6201/483590.09Tabassum et al, 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }721256/12090.751.14 (0.99-1.31)6C6orf57rs1048886GSim et al, 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1001363", "ISSN" : "1553-7404", "PMID" : "21490949", "abstract" : "Recent large genome-wide association studies (GWAS) have identified multiple loci which harbor genetic variants associated with type 2 diabetes mellitus (T2D), many of which encode proteins not previously suspected to be involved in the pathogenesis of T2D. Most GWAS for T2D have focused on populations of European descent, and GWAS conducted in other populations with different ancestry offer a unique opportunity to study the genetic architecture of T2D. We performed genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945 controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians (977 cases, 1,169 controls). In addition to the search for novel variants implicated in T2D, these multi-ethnic cohorts serve to assess the transferability and relevance of the previous findings from European descent populations in the three major ethnic populations of Asia, comprising half of the world's population. Of the SNPs associated with T2D in previous GWAS, only variants at CDKAL1 and HHEX/IDE/KIF11 showed the strongest association with T2D in the meta-analysis including all three ethnic groups. However, consistent direction of effect was observed for many of the other SNPs in our study and in those carried out in European populations. Close examination of the associations at both the CDKAL1 and HHEX/IDE/KIF11 loci provided some evidence of locus and allelic heterogeneity in relation to the associations with T2D. We also detected variation in linkage disequilibrium between populations for most of these loci that have been previously identified. These factors, combined with limited statistical power, may contribute to the failure to detect associations across populations of diverse ethnicity. These findings highlight the value of surveying across diverse racial/ethnic groups towards the fine-mapping efforts for the casual variants and also of the search for variants, which may be population-specific.", "author" : [ { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Rick Twee-Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan-Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik-Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E-Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "editor" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Greg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "4" ] ] }, "page" : "e1001363", "publisher" : "Public Library of Science", "title" : "Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "74", "plainTextFormattedCitation" : "74", "previouslyFormattedCitation" : "74" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }74977/11690.181.54 (1.32-1.80)1.54 (1.32-1.80)(p=8.32×10–8)0.171.01 (0.97-1.06)(p=0.56)12171/56862<0.012GRB14rs3923113AKooner et al, 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7118731/398560.741.09 (1.06-1.13)1.09 (1.06-1.13)(p=2.06×10–7)0.611.04 (1.00-1.08)(p=0.03)9580/538100.07Tabassum et al, 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }721256/12090.761.15 (0.99-1.33)15HMG20Ars7178572GKooner et al, 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7118731/398560.521.09 (1.06-1.12)1.09 (1.06-1.12)(p=1.94×10–9)0.681.08 (1.05-1.10)c(p=2.17×10–8)22669/581190.62Tabassum et al, 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }721256/12090.511.15 (1.02-1.30)20HNF4α rs4812829AKooner et al, 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7118731/398560.291.09 (1.06-1.12)1.13 (1.02-1.26)(p=0.02)0.161.07 (1.02-1.12)(p=0.01)9580/538100.35Tabassum et al, 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }721256/12090.281.15 (1.02-1.30)10VPS26Ars1802295TKooner et al, 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }7118731/398560.261.08 (1.05-1.12)1.08 (1.06-1.10)(p=3.02×10–15)0.271.02 (0.98-1.06)(p=0.28)12171/568620.01Tabassum et al, 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }721256/12090.271.09 (0.95-1.25)2TMEM163drs6723108TTabassum et al, 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }721256/12090.871.31 (1.20-1.44)1.31 (1.20-1.44)(p=1.26×10–8)0.621.01 (0.97-1.04)(p=0.71)9580/53810<0.01aORs are from meta-analysis of studies, where applicablebRAF from 1,000 genomes (EUR)cEstimate obtained from stage 2 (sample size is an approximate); found to be significantly associated with type 2 diabetes in white CaucasiansdOR adjusted for age and sex2.3.4 Population burdenAll sixteen SNPs, which were significantly associated with type 2 diabetes in South Asians, were included in the genotype score (ADCY5, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B, FTO, GLIS3, HHEX, PPARG, SLC30A8, TCF7L2 rs7903146 and rs12255372, CHCHD9, KCNQ1 rs2237892 and rs2237897, IGF2BP2 and HMG20A SNPs from Table 2.1 and Figure 2.3). RAFs for both ethnicities were weighed by White Caucasian summary ORs from DIAGRAM because our primary analysis showed that individual risk estimates did not vary, and due to a larger sample, we expect the White Caucasian estimates to be more precise. Using this approach, no significant difference in the population burden was observed (P=0.85) (Figure 2.5).Figure 2. SEQ Figure \* ARABIC 5 Genotype score (with 95% confidence intervals) of SNPs in South Asians and white Caucasians. The genotype score was constructed using effect estimates and RAFs from SNPs common to both groups2.4 DiscussionTwenty-four SNPs were associated with type 2 diabetes in South Asians, eight of which were novel, discovered from GWAS. There were some variations in RAFs but the effect sizes for common SNPs did not differ between the ethnic groups. Interestingly, only three of the novel SNPs discovered from the South Asian GWAS were nominally associated with type 2 diabetes in white Caucasians. Overall, the population burden from type 2 diabetes SNPs estimated using a genotype score appears to be comparable in both ethnicities.2.4.1 SNPs associated with type 2 diabetes from meta-analysis of South Asian studiesMeta-analysis of risk alleles for most SNPs increased the odds of type 2 diabetes by 15-35% among South Asians. Notable exceptions were the KCNQ1 SNPs, which showed prominent ORs for type 2 diabetes. KCNQ1 SNPs have been shown as a more significant contributor to type 2 diabetes than other loci in other Asian populationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/hmg/ddp294", "ISSN" : "1460-2083", "PMID" : "19556355", "abstract" : "Common variants in KCNQ1 have recently been reported to be associated with type 2 diabetes in East Asians. We aimed to examine whether these common variants (rs2074196, rs2237892, rs2237895 and rs2237897) were also associated with type 2 diabetes in a population-based cohort of 3210 Chinese Hans and to explore the underlying mechanisms. The SNPs rs2237892, rs2237895 and rs2237897 were significantly associated with type 2 diabetes (OR: 1.33-1.36, P <or= 0.0009), impaired fasting glucose (IFG) (OR: 1.16-1.19, P <or= 0.0193) and combined IFG/type 2 diabetes (OR: 1.23-1.24, P <or= 0.0004), and the corresponding population attributable risks of type 2 diabetes for the three SNPs were 32.5, 18.8 and 35.8%, respectively. However, rs2074196 showed a weak, but significant association with IFG (OR: 1.18 [1.04-1.33], P = 0.009) and combined IFG/type 2 diabetes (OR: 1.17 [1.05-1.30], P = 0.0053), as well as a trend toward association with type 2 diabetes (OR: 1.15 [0.98-1.35], P = 0.0882), suggesting a different pattern of association when compared with the other three SNPs. The four SNPs were all significantly associated with HOMA-B (P <or= 0.042) while rs2237895 and rs22378897 also showed significant association with fasting glucose (P <or= 0.012). Notably, the associations with type 2 diabetes were markedly attenuated after adjusting for HOMA-B (OR(rs2237892): 1.33 [1.05-1.68], P = 0.018; OR(rs2237895): 1.24 [1.00-1.54], P = 0.0524; OR(rs2237897): 1.22[0.98-1.53], P = 0.09). Moreover, GCCC haplotype showed similar associations with type 2 diabetes (OR: 1.48 [1.17-1.85], P = 0.0008), IFG (OR: 1.32 [1.10-1.57], P = 0.0023), combined IFG/type 2 diabetes (OR: 1.37 [1.17-1.61], P = 8.7 x 10(-5)), and lower HOMA-B values (beta = -4.41 +/- 1.62, P = 0.006). These results suggest that KCNQ1 is a major type 2 diabetes gene in the Chinese Hans and it may confer type 2 diabetes risk by impaired beta-cell function.", "author" : [ { "dropping-particle" : "", "family" : "Qi", "given" : "Qibin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Huaixing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Hongyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yu", "given" : "Zhijie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Xu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Human molecular genetics", "id" : "ITEM-1", "issue" : "18", "issued" : { "date-parts" : [ [ "2009", "9", "15" ] ] }, "page" : "3508-15", "title" : "Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "97", "plainTextFormattedCitation" : "97", "previouslyFormattedCitation" : "97" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }97 and because both SNPs (in weak LD) with larger ORs are located on the same gene, it appears that KCNQ1 may truly have a stronger signal in South Asians than in whites. However, the exceptionally large effect size for KCNQ1 rs2237897 is likely to be inaccurate, given the wide CIs and inconsistency with GWAS estimates from Caucasians and East Asians (OR 1.33, 95% CI 1.24-1.41)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.208", "ISSN" : "1061-4036", "PMID" : "18711366", "abstract" : "We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).", "author" : [ { "dropping-particle" : "", "family" : "Unoki", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takahashi", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawaguchi", "given" : "Takahisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horikoshi", "given" : "Momoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel P K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmkvist", "given" : "Johan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nurbaya", "given" : "Siti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsunoda", "given" : "Tatsuhiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubo", "given" : "Michiaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babazono", "given" : "Tetsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirose", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayashi", "given" : "Matsuhiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iwamoto", "given" : "Yasuhiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kashiwagi", "given" : "Atsunori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaku", "given" : "Kohei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawamori", "given" : "Ryuzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamatani", "given" : "Naoyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kikkawa", "given" : "Ryuichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Yusuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "page" : "1098-102", "title" : "SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "98", "plainTextFormattedCitation" : "98", "previouslyFormattedCitation" : "98" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }98. Moreover, the KCNQ1 rs2237897 association was reported in only two studies among South Asians and thus could be a product of the winner’s curseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/EDE.0b013e318181b865", "ISSN" : "1531-5487", "PMID" : "18703928", "abstract" : "The estimated effect of a marker allele from the initial study reporting the marker-allele association is often exaggerated relative to the estimated effect in follow-up studies (the \"winner's curse\" phenomenon). This is a particular concern for genome-wide association studies, where markers typically must pass very stringent significance thresholds to be selected for replication. A related problem is the overestimation of the predictive accuracy that occurs when the same data set is used to select a multilocus risk model from a wide range of possible models and then estimate the accuracy of the final model (\"over-fitting\"). Even in the absence of these quantitative biases, researchers can over-state the qualitative importance of their findings--for example, by focusing on relative risks in a context where sensitivity and specificity may be more appropriate measures. Epidemiologists need to be aware of these potential problems: as authors, to avoid or minimize them, and as readers, to detect them.", "author" : [ { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Epidemiology (Cambridge, Mass.)", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "page" : "649-51; discussion 657-8", "title" : "Curses--winner's and otherwise--in genetic epidemiology.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "99", "plainTextFormattedCitation" : "99", "previouslyFormattedCitation" : "99" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }99.Fifteen GWAS signals for type 2 diabetes in white Caucasians, East Asians, and Singaporean MalayADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1000847", "ISSN" : "1553-7404", "PMID" : "20174558", "abstract" : "To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.", "author" : [ { "dropping-particle" : "", "family" : "Tsai", "given" : "Fuu-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Chi-Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Ching-Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chuang", "given" : "Lee-Ming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Chieh-Hsiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Chwen-Tzuei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Tzu-Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Rong-Hsing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiu", "given" : "Chiung-Fang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yi-Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Chih-Chun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Pei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chien-Hsiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fann", "given" : "Cathy S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuan-Tsong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jer-Yuarn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "e1000847", "title" : "A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.120", "ISSN" : "1546-1718", "PMID" : "18372903", "abstract" : "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchini", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tianle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bostr\u00f6m", "given" : "Kristina Bengtsson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Chia-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duren", "given" : "William L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubalanza", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuruvilla", "given" : "Finny G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marvelle", "given" : "Amanda F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettersen", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qin", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roix", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Anelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6gren", "given" : "Marketa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "638-45", "title" : "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/ng.609", "ISSN" : "1546-1718", "PMID" : "20581827", "abstract" : "By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.", "author" : [ { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "Ryan P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huth", "given" : "Cornelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amin", "given" : "Najaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Guanming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steve A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofmann", "given" : "Oliver M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segr\u00e8", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blagieva", "given" : "Roza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson Bostr\u00f6m", "given" : "Kristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bravenboer", "given" : "Bert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "Nois\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ganser", "given" : "Martha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Green", "given" : "Todd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffin", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen H L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lieverse", "given" : "Aloysius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meitinger", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petersen", "given" : "Ann-Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurdsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strassburger", "given" : "Klaus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haeften", "given" : "Timon W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpt", "given" : "Thijs", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Vliet-Ostaptchouk", "given" : "Jana", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jacqueline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hide", "given" : "Winston A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stein", "given" : "Lincoln D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H-Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "579-89", "publisher" : "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.", "title" : "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.2337/db12-0454", "ISSN" : "1939-327X", "PMID" : "22961080", "abstract" : "Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 \u00d7 10(-9)) and RASGRP1 (rs7403531: P = 3.9 \u00d7 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of \u03b2-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "Huaixing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gan", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dong", "given" : "Xiao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xueyao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Liang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bao", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Pengtao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "He", "given" : "Meian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Liangdan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Yiqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Jingwen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ning", "given" : "Qianqian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tang", "given" : "Yong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wen", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Di", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Xilin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guo", "given" : "Kunquan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zuo", "given" : "Xianbo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guo", "given" : "Xiaohui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Handong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhou", "given" : "Xianghai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xuejun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Tangchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Liegang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Ze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Renming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jia", "given" : "Weiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ji", "given" : "Linong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yixue", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Xu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "291-8", "title" : "A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "100\u2013103", "plainTextFormattedCitation" : "100\u2013103", "previouslyFormattedCitation" : "100\u2013103" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }100–103 were not associated with type 2 diabetes in our South Asian meta-analysis. This may reflect the low power to detect similar effect sizes for ADAMTS9 rs4607103, CDC123 rs12779790, JAZF1 rs864746, KCNQ1 rs231362, DGKT rs2191349, GCK rs1799884, GCKR rs780094, MTNR1B rs10830963, PROX1 rs340874, and TSPAN8 rs7961581 (Table 2.2) and either a true lack of association for KCNJ11 rs5219, KCNQ1 rs2237895, NOTCH2 rs10923931, THADA rs7578597 and WFS1 rs10010131 or significant between-study heterogeneity as we were adequately powered for the last five SNPs (Table 2.2). KCNJ11 rs5219 in particular was close to significance (OR 1.19. 95% CI 0.98-1.45) and demonstrated a high degree of heterogeneity (I2=81%, P<0.01).2.4.2 Comparison of effect sizes, RAF and risk alleles between South Asians and white CaucasiansIn general when comparing effect sizes of SNPs associated with type 2 diabetes from our meta-analysis with DIAGRAM estimates in white Caucasians, the risk from SNPs predisposing to type 2 diabetes did not differ substantially between the groups. However, the point estimates were more precise and CIs tighter among the white Caucasians because of the larger sample size. Our observation of no significant difference in risk estimates is not surprising because SNPs evaluated in South Asians are selected for homogeneity as they were first discovered in white Caucasians and then replicated in South Asians. If there is a difference in genetic risk between the ethnic groups, it probably does not result from polymorphisms common to both groups. The results of our paper are supported by those recently published by DIAGRAM, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, and South Asian Type 2 Diabetes (SAT2D) ConsortiumADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2897", "ISSN" : "1546-1718", "PMID" : "24509480", "abstract" : "To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.", "author" : [ { "dropping-particle" : "", "family" : "DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "South Asian Type 2 Diabetes (SAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mexican American Type 2 Diabetes (MAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Go", "given" : "Min Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Below", "given" : "Jennifer E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horikoshi", "given" : "Momoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Maggie C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adair", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldassarre", "given" : "Damiano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bao", "given" : "Yuqian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "Graeme I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Qiuyin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carey", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "Juliana C N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Li-Ching", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Tien-Jyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yi-Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chien-Hsiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuan-Tsong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Nam H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Young Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chuang", "given" : "Lee-Ming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crenshaw", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donnelly", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorkhan", "given" : "Mozhgan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Josee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edkins", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erbel", "given" : "Raimund", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Escobedo", "given" : "Jorge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esko", "given" : "Tonu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eury", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontanillas", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsen", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraser", "given" : "Ross M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gao", "given" : "Yutang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gertow", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Bok-Ghee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmen", "given" : "Oddgeir L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hovingh", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hreidarsson", "given" : "Astradur B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunt", "given" : "Sarah E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikegami", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jia", "given" : "Weiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jockel", "given" : "Karl-Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Hyun Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen Hong L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "Ann M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Hassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hyung-Lae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Sangsoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Young Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinnunen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korpi-Hyovalti", "given" : "Eeva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kravic", "given" : "Jasmina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krithika", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Ashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumate", "given" : "Jesus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwak", "given" : "Soo Heon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langford", "given" : "Cordelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leander", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jen-Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Nanette R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindholm", "given" : "Eero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jian Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Long", "given" : "Jirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ma", "given" : "Ronald C W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mannisto", "given" : "Satu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metspalu", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mirza", "given" : "Ghazala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mihailov", "given" : "Evelin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moebus", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muhleisen", "given" : "Thomas W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muller-Nurasyid", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musk", "given" : "Bill", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Jiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakashima", "given" : "Eitaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Njolstad", "given" : "Inger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nothen", "given" : "Markus M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohnaka", "given" : "Keizo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Twee Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Kyong Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkin", "given" : "Melissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pechlivanis", "given" : "Sonali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl G P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Jackie F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rallidis", "given" : "Loukianos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossin", "given" : "Elizabeth J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saltevo", "given" : "Juha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saramies", "given" : "Jouko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segre", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shu", "given" : "Xiao Ou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigur[eth]sson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sivapalaratnam", "given" : "Suthesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "So", "given" : "Wing Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stancakova", "given" : "Alena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinbach", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syvanen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takayanagi", "given" : "Ryoichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teslovich", "given" : "Tanya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tikkanen", "given" : "Emmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trakalo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tremoli", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trip", "given" : "Mieke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Fuu Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valladares-Salgado", "given" : "Adan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vedantam", "given" : "Sailaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veglia", "given" : "Fabrizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Congrong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wennauer", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilsgaard", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiltshire", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winckler", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jer-Yuarn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Loic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokota", "given" : "Mitsuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabaneh", "given" : "Delilah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowden", "given" : "Donald W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Nancy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruz", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanis", "given" : "Craig L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jong-Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parra", "given" : "Esteban J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "3" ] ] }, "page" : "234-44", "publisher" : "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.", "title" : "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "104", "plainTextFormattedCitation" : "104", "previouslyFormattedCitation" : "104" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }104. Their study also found effect estimates for common SNPs predisposing to type 2 diabetes to be homogenous among South Asians and white Caucasians. In addition to the recently published study, we show that the genotype score, which measures population burden in both groups, does not differ. Our conclusion that the genetic risk for type 2 diabetes probably does not differ between the two ethnicities is greatly strengthened by this recent publication.Table 2. SEQ Table_2. \* ARABIC 2 SNPs associated with type 2 diabetes in published GWA-studies from white Caucasians but not replicated in South Asian meta-analysisChr.GeneSNPGWAS estimateSouth Asian meta-analysisDirectioncCases in current meta-analysisPower in this meta-analysisCase–control pair needed for 80% powerReference OR (95% CI)aOR (95% CI)bRAF3ADAMTS9rs4607103Zeggini et al, 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.120", "ISSN" : "1546-1718", "PMID" : "18372903", "abstract" : "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchini", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tianle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bostr\u00f6m", "given" : "Kristina Bengtsson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Chia-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duren", "given" : "William L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubalanza", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuruvilla", "given" : "Finny G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marvelle", "given" : "Amanda F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettersen", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qin", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roix", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Anelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6gren", "given" : "Marketa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "638-45", "title" : "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "101", "plainTextFormattedCitation" : "101", "previouslyFormattedCitation" : "101" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1011.09 (1.06-1.12)1.01 (0.90-1.14)0.50+23070.54423110CDC123rs12779790Zeggini et al, 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.120", "ISSN" : "1546-1718", "PMID" : "18372903", "abstract" : "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchini", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tianle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bostr\u00f6m", "given" : "Kristina Bengtsson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Chia-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duren", "given" : "William L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubalanza", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuruvilla", "given" : "Finny G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marvelle", "given" : "Amanda F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettersen", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qin", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roix", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Anelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6gren", "given" : "Marketa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "638-45", "title" : "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "101", "plainTextFormattedCitation" : "101", "previouslyFormattedCitation" : "101" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1011.11 (1.07-1.14)1.11 (0.97-1.27)0.14+40490.6561357JAZF1rs864745Zeggini et al, 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.120", "ISSN" : "1546-1718", "PMID" : "18372903", "abstract" : "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchini", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tianle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bostr\u00f6m", "given" : "Kristina Bengtsson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Chia-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duren", "given" : "William L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubalanza", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuruvilla", "given" : "Finny G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marvelle", "given" : "Amanda F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettersen", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qin", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roix", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Anelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6gren", "given" : "Marketa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "638-45", "title" : "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "101", "plainTextFormattedCitation" : "101", "previouslyFormattedCitation" : "101" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1011.10 (1.07-1.13)1.08 (0.96-1.22)0.71+40550.78428511KCNQ1rs2237895Tsai et al, 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1000847", "ISSN" : "1553-7404", "PMID" : "20174558", "abstract" : "To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.", "author" : [ { "dropping-particle" : "", "family" : "Tsai", "given" : "Fuu-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Chi-Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Ching-Chu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chuang", "given" : "Lee-Ming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Chieh-Hsiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Chwen-Tzuei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Tzu-Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Rong-Hsing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shiu", "given" : "Chiung-Fang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yi-Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Chih-Chun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Pei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chien-Hsiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fann", "given" : "Cathy S J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuan-Tsong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jer-Yuarn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "e1000847", "title" : "A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "100", "plainTextFormattedCitation" : "100", "previouslyFormattedCitation" : "100" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1001.29 (1.19-1.40)1.12 (0.96-1.31)0.42+14240.994967DGKT rs2191349Dupuis et al, 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.520", "ISSN" : "1546-1718", "PMID" : "20081858", "abstract" : "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henneman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dehghan", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lajunen", "given" : "Taina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabena", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sethupathy", "given" : "Praveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariyurek", "given" : "Yavuz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barter", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochud", "given" : "Murielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crisponi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Ian N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fedson", "given" : "Annette C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Rosinsky", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frants", "given" : "Rune", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwilliam", "given" : "Rhian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xijing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hillman", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesaniemi", "given" : "Y Antero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskinen", "given" : "Seppo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahley", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Larrad", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukherjee", "given" : "Sutapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naitza", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00f9", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paolisso", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattaro", "given" : "Cristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Andreas F H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posthuma", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolandsson", "given" : "Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurethsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Laila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijk", "given" : "Ko Willems", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visvikis-Siest", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogelzangs", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "Kim L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jaqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnell", "given" : "John W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zethelius", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spranger", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-R\u00edos", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "105-16", "title" : "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "10", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "10" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }101.06 (1.04-1.08)1.04 (0.85-1.27)0.61+16320.2197717GCKrs1799884Dupuis et al, 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.520", "ISSN" : "1546-1718", "PMID" : "20081858", "abstract" : "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henneman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dehghan", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lajunen", "given" : "Taina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabena", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sethupathy", "given" : "Praveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariyurek", "given" : "Yavuz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barter", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochud", "given" : "Murielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crisponi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Ian N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fedson", "given" : "Annette C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Rosinsky", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frants", "given" : "Rune", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwilliam", "given" : "Rhian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xijing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hillman", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesaniemi", "given" : "Y Antero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskinen", "given" : "Seppo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahley", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Larrad", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukherjee", "given" : "Sutapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naitza", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00f9", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paolisso", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattaro", "given" : "Cristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Andreas F H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posthuma", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolandsson", "given" : "Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurethsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Laila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijk", "given" : "Ko Willems", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visvikis-Siest", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogelzangs", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "Kim L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jaqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnell", "given" : "John W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zethelius", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spranger", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-R\u00edos", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "105-16", "title" : "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "10", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "10" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }101.07 (1.05-1.10)0.92 (0.73-1.15)0.14+16700.1613,9717GCKRrs780094Dupuis et al, 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.520", "ISSN" : "1546-1718", "PMID" : "20081858", "abstract" : "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henneman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dehghan", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lajunen", "given" : "Taina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabena", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sethupathy", "given" : "Praveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariyurek", "given" : "Yavuz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barter", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochud", "given" : "Murielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crisponi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Ian N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fedson", "given" : "Annette C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Rosinsky", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frants", "given" : "Rune", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwilliam", "given" : "Rhian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xijing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hillman", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesaniemi", "given" : "Y Antero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskinen", "given" : "Seppo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahley", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Larrad", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukherjee", "given" : "Sutapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naitza", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00f9", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paolisso", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattaro", "given" : "Cristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Andreas F H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posthuma", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolandsson", "given" : "Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurethsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Laila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijk", "given" : "Ko Willems", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visvikis-Siest", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogelzangs", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "Kim L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jaqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnell", "given" : "John W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zethelius", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spranger", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-R\u00edos", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "105-16", "title" : "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "10", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "10" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }101.06 (1.04-1.08)1.07 (0.96-1.19)0.76+40550.3512,83311KCNJ11rs5219Scott et al., 2007 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1126/science.1142382", "ISSN" : "1095-9203", "PMID" : "17463248", "abstract" : "Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.", "author" : [ { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duren", "given" : "William L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokunina-Olsson", "given" : "Ludmila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Chia-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tianle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pruim", "given" : "Randall", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xiao", "given" : "Rui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xiao-Yi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conneely", "given" : "Karen N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riebow", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sprau", "given" : "Andrew G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tong", "given" : "Maurine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Peggy P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hetrick", "given" : "Kurt N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnhart", "given" : "Michael W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bark", "given" : "Craig W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldstein", "given" : "Janet L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Lee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xiang", "given" : "Fang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saramies", "given" : "Jouko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinnunen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pugh", "given" : "Elizabeth W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doheny", "given" : "Kimberly F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Science (New York, N.Y.)", "id" : "ITEM-1", "issue" : "5829", "issued" : { "date-parts" : [ [ "2007", "6", "1" ] ] }, "page" : "1341-5", "title" : "A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.", "type" : "article-journal", "volume" : "316" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "105", "plainTextFormattedCitation" : "105", "previouslyFormattedCitation" : "105" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1051.14 (1.10-1.19)1.19 (0.98-1.45)0.37+56431.0019397PROX1rs340874Dupuis et al, 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.520", "ISSN" : "1546-1718", "PMID" : "20081858", "abstract" : "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henneman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dehghan", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lajunen", "given" : "Taina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabena", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sethupathy", "given" : "Praveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariyurek", "given" : "Yavuz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barter", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochud", "given" : "Murielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crisponi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Ian N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fedson", "given" : "Annette C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Rosinsky", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frants", "given" : "Rune", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwilliam", "given" : "Rhian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xijing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hillman", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesaniemi", "given" : "Y Antero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskinen", "given" : "Seppo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahley", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Larrad", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukherjee", "given" : "Sutapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naitza", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00f9", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paolisso", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattaro", "given" : "Cristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Andreas F H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posthuma", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolandsson", "given" : "Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurethsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Laila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijk", "given" : "Ko Willems", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visvikis-Siest", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogelzangs", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "Kim L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jaqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnell", "given" : "John W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zethelius", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spranger", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-R\u00edos", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "105-16", "title" : "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "10", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "10" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }101.07 (1.05-1.09)0.96 (0.83-1.11)0.58+16260.27707311MTNR1Brs10830963Dupuis et al, 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.520", "ISSN" : "1546-1718", "PMID" : "20081858", "abstract" : "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henneman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dehghan", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lajunen", "given" : "Taina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabena", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sethupathy", "given" : "Praveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariyurek", "given" : "Yavuz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barter", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochud", "given" : "Murielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crisponi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Ian N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fedson", "given" : "Annette C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Rosinsky", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frants", "given" : "Rune", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwilliam", "given" : "Rhian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xijing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hillman", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesaniemi", "given" : "Y Antero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskinen", "given" : "Seppo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahley", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Larrad", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukherjee", "given" : "Sutapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naitza", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00f9", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paolisso", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattaro", "given" : "Cristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Andreas F H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posthuma", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolandsson", "given" : "Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurethsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Laila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijk", "given" : "Ko Willems", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visvikis-Siest", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogelzangs", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "Kim L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jaqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnell", "given" : "John W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zethelius", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spranger", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-R\u00edos", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "105-16", "title" : "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "10", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "10" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }101.09 (1.06-1.12)1.01 (0.91-1.11)0.40+34750.7043772THADArs7578597Zeggini et al, 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.120", "ISSN" : "1546-1718", "PMID" : "18372903", "abstract" : "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchini", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tianle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bostr\u00f6m", "given" : "Kristina Bengtsson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Chia-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duren", "given" : "William L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubalanza", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuruvilla", "given" : "Finny G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marvelle", "given" : "Amanda F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettersen", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qin", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roix", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Anelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6gren", "given" : "Marketa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "638-45", "title" : "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "101", "plainTextFormattedCitation" : "101", "previouslyFormattedCitation" : "101" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1011.15 (1.10-1.20)1.05 (0.92-1.20)0.86+40900.86331311KCNQ1rs231362Voight et al, 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.609", "ISSN" : "1546-1718", "PMID" : "20581827", "abstract" : "By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.", "author" : [ { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "Ryan P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huth", "given" : "Cornelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amin", "given" : "Najaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Guanming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steve A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofmann", "given" : "Oliver M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segr\u00e8", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blagieva", "given" : "Roza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson Bostr\u00f6m", "given" : "Kristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bravenboer", "given" : "Bert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "Nois\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ganser", "given" : "Martha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Green", "given" : "Todd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffin", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen H L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lieverse", "given" : "Aloysius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meitinger", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petersen", "given" : "Ann-Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurdsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strassburger", "given" : "Klaus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haeften", "given" : "Timon W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpt", "given" : "Thijs", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Vliet-Ostaptchouk", "given" : "Jana", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jacqueline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hide", "given" : "Winston A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stein", "given" : "Lincoln D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H-Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "579-89", "publisher" : "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.", "title" : "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "102", "plainTextFormattedCitation" : "102", "previouslyFormattedCitation" : "102" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1021.08 (1.06-1.10)1.15 (0.97-1.36)0.75+30520.4568471NOTCH2rs10923931Zeggini et al, 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.120", "ISSN" : "1546-1718", "PMID" : "18372903", "abstract" : "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchini", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tianle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bostr\u00f6m", "given" : "Kristina Bengtsson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Chia-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duren", "given" : "William L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubalanza", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuruvilla", "given" : "Finny G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marvelle", "given" : "Amanda F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettersen", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qin", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roix", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Anelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6gren", "given" : "Marketa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "638-45", "title" : "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "101", "plainTextFormattedCitation" : "101", "previouslyFormattedCitation" : "101" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1011.13 (1.08-1.17)1.06 (0.94-1.19)0.21+40350.89358112TSPAN8rs7961581Zeggini et al, 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.120", "ISSN" : "1546-1718", "PMID" : "18372903", "abstract" : "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchini", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Tianle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bostr\u00f6m", "given" : "Kristina Bengtsson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Chia-Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duren", "given" : "William L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hughes", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubalanza", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuruvilla", "given" : "Finny G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marvelle", "given" : "Amanda F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pettersen", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qin", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roix", "given" : "Jeffrey J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Anelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6gren", "given" : "Marketa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "638-45", "title" : "Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "101", "plainTextFormattedCitation" : "101", "previouslyFormattedCitation" : "101" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1011.09 (1.06-1.12)1.05 (0.95-1.16)0.33+39770.7348654WFS1rs10010131dVoight et al, 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.609", "ISSN" : "1546-1718", "PMID" : "20581827", "abstract" : "By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.", "author" : [ { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "Ryan P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huth", "given" : "Cornelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amin", "given" : "Najaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Guanming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steve A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofmann", "given" : "Oliver M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segr\u00e8", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blagieva", "given" : "Roza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bengtsson Bostr\u00f6m", "given" : "Kristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bravenboer", "given" : "Bert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "Nois\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ganser", "given" : "Martha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Green", "given" : "Todd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Griffin", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen H L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lieverse", "given" : "Aloysius", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meitinger", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petersen", "given" : "Ann-Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurdsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strassburger", "given" : "Klaus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haeften", "given" : "Timon W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpt", "given" : "Thijs", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Vliet-Ostaptchouk", "given" : "Jana", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jacqueline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hide", "given" : "Winston A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stein", "given" : "Lincoln D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H-Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "579-89", "publisher" : "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.", "title" : "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "102", "plainTextFormattedCitation" : "102", "previouslyFormattedCitation" : "102" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }1021.13 (1.08-1.18)1.05 (0.96-1.15)0.72+50220.972472aORs are from the referenced GWASbORs are from the South Asian meta-analysisc+ is the same direction of effectdGWAS significant SNP rs1801214 is in LD (r2=1) with reported SNPFigure 2.4 depicts overlap between genes associated with type 2 diabetes in South Asians and white Caucasians. Considerably more signals have been identified in whites due to the greater number of GWAS. Because a majority of signals were replicated in our meta-analysis, it is unlikely that they are unique to white Caucasians. Rather, larger GWAS with greater than 36,000 case/control pairs are required to detect ORs as low as 1.05 with an RAF of 10%. The four GWAS in South Asians represent about 25,704 cases and 43,688 controls, therefore more GWAS in South Asians alone will detect small effects and discover SNPs unique to this group, and ultimately facilitate further elucidation of the genetic basis of type 2 diabetes in this group.We did not find a trend in RAFs; specifically, RAFs were not consistently higher in South Asians. Risk alleles from six SNPs in this analysis were the major/common alleles in both ethnicities. Negative selection usually prevents risk alleles from becoming common unless they are advantageousADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.tig.2005.08.007", "ISSN" : "0168-9525", "PMID" : "16153740", "abstract" : "Unlike rare mendelian diseases, which are due to new mutations (i.e. derived alleles), several alleles that increase the risk to common diseases are ancestral. Moreover, population genetics studies suggest that some derived alleles that protect against common diseases became advantageous recently. These observations can be explained within an evolutionary framework in which ancestral alleles reflect ancient adaptations to the lifestyle of ancient human populations, whereas the derived alleles were deleterious. However, with the shift in environment and lifestyle, the ancestral alleles now increase the risk of common diseases in modern populations. In this article, we develop an explicit evolutionary model and use population genetics simulations to investigate the expected haplotype structure and type of disease-association signals of ancestral risk alleles.", "author" : [ { "dropping-particle" : "", "family" : "Rienzo", "given" : "Anna", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hudson", "given" : "Richard R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Trends in genetics : TIG", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "page" : "596-601", "title" : "An evolutionary framework for common diseases: the ancestral-susceptibility model.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "106", "plainTextFormattedCitation" : "106", "previouslyFormattedCitation" : "106" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }106. Risk alleles for genes encouraging fat storage may have been advantageous in ancient environments with unpredictable food supply and high level of activity, but now could predispose to type 2 diabetesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.tig.2005.08.007", "ISSN" : "0168-9525", "PMID" : "16153740", "abstract" : "Unlike rare mendelian diseases, which are due to new mutations (i.e. derived alleles), several alleles that increase the risk to common diseases are ancestral. Moreover, population genetics studies suggest that some derived alleles that protect against common diseases became advantageous recently. These observations can be explained within an evolutionary framework in which ancestral alleles reflect ancient adaptations to the lifestyle of ancient human populations, whereas the derived alleles were deleterious. However, with the shift in environment and lifestyle, the ancestral alleles now increase the risk of common diseases in modern populations. In this article, we develop an explicit evolutionary model and use population genetics simulations to investigate the expected haplotype structure and type of disease-association signals of ancestral risk alleles.", "author" : [ { "dropping-particle" : "", "family" : "Rienzo", "given" : "Anna", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hudson", "given" : "Richard R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Trends in genetics : TIG", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "page" : "596-601", "title" : "An evolutionary framework for common diseases: the ancestral-susceptibility model.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "106", "plainTextFormattedCitation" : "106", "previouslyFormattedCitation" : "106" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }106. To this end, literature examining evidence of selection for type 2 diabetes variants has shown inconsistent resultsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1101/gr.087577.108", "ISSN" : "1088-9051", "PMID" : "19307593", "abstract" : "Genome-wide scans for recent positive selection in humans have yielded insight into the mechanisms underlying the extensive phenotypic diversity in our species, but have focused on a limited number of populations. Here, we present an analysis of recent selection in a global sample of 53 populations, using genotype data from the Human Genome Diversity-CEPH Panel. We refine the geographic distributions of known selective sweeps, and find extensive overlap between these distributions for populations in the same continental region but limited overlap between populations outside these groupings. We present several examples of previously unrecognized candidate targets of selection, including signals at a number of genes in the NRG-ERBB4 developmental pathway in non-African populations. Analysis of recently identified genes involved in complex diseases suggests that there has been selection on loci involved in susceptibility to type II diabetes. Finally, we search for local adaptation between geographically close populations, and highlight several examples.", "author" : [ { "dropping-particle" : "", "family" : "Pickrell", "given" : "Joseph K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coop", "given" : "Graham", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Novembre", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kudaravalli", "given" : "Sridhar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Jun Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Absher", "given" : "Devin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinivasan", "given" : "Balaji S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barsh", "given" : "Gregory S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Myers", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feldman", "given" : "Marcus W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pritchard", "given" : "Jonathan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genome research", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5" ] ] }, "page" : "826-37", "title" : "Signals of recent positive selection in a worldwide sample of human populations.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0102645", "ISSN" : "1932-6203", "PMID" : "25115870", "abstract" : "The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.", "author" : [ { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turro", "given" : "Ernest", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "William R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "Sian-Tsung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afzal", "given" : "Uzma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afaq", "given" : "Saima", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehne", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Reilly", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lavery", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandrovcova", "given" : "Jana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wass", "given" : "Mark N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Kathryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oozageer", "given" : "Laticia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Ishminder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Hussaini", "given" : "Abtehale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mills", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grewal", "given" : "Jagvir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Panoulas", "given" : "Vasileios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewin", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Northwood", "given" : "Korrinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geoghegan", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yingrui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aitman", "given" : "Timothy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butcher", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "1", "12" ] ] }, "page" : "e102645", "title" : "The South Asian genome.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.ajhg.2013.12.010", "ISSN" : "1537-6605", "PMID" : "24412096", "abstract" : "We have investigated the evidence for positive selection in samples of African, European, and East Asian ancestry at 65 loci associated with susceptibility to type 2 diabetes (T2D) previously identified through genome-wide association studies. Selection early in human evolutionary history is predicted to lead to ancestral risk alleles shared between populations, whereas late selection would result in population-specific signals at derived risk alleles. By using a wide variety of tests based on the site frequency spectrum, haplotype structure, and population differentiation, we found no global signal of enrichment for positive selection when we considered all T2D risk loci collectively. However, in a locus-by-locus analysis, we found nominal evidence for positive selection at 14 of the loci. Selection favored the protective and risk alleles in similar proportions, rather than the risk alleles specifically as predicted by the thrifty gene hypothesis, and may not be related to influence on diabetes. Overall, we conclude that past positive selection has not been a powerful influence driving the prevalence of T2D risk alleles.", "author" : [ { "dropping-particle" : "", "family" : "Ayub", "given" : "Qasim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moutsianas", "given" : "Loukas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Panoutsopoulou", "given" : "Kalliope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colonna", "given" : "Vincenza", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pagani", "given" : "Luca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ritchie", "given" : "Graham R S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tyler-Smith", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xue", "given" : "Yali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2", "6" ] ] }, "language" : "English", "page" : "176-85", "publisher" : "Elsevier", "title" : "Revisiting the Thrifty Gene Hypothesis via 65 Loci Associated with Susceptibility to Type 2 Diabetes.", "type" : "article-journal", "volume" : "94" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "107\u2013109", "plainTextFormattedCitation" : "107\u2013109", "previouslyFormattedCitation" : "107\u2013109" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }107–109.2.4.3 Testing novel SNPs discovered from South Asians GWA-studies in white CaucasiansFinally, we tested novel SNPs derived from South Asians in white Caucasians; only three were associated with type 2 diabetes. Interestingly, one of the novel SNPs, rs1048886, is a functional missense mutation resulting in a change from glutamine to arginine in the UPF0369 protein involved in immune responseADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1534/genetics.109.107540", "ISSN" : "1943-2631", "PMID" : "19805818", "abstract" : "Innate immunity is the first line of defense against microbial infections. Although polymorphisms in toll-like receptors (TLRs) and downstream signaling molecules (CD14, TLR2, TLR4, TLR5, and IRAK4) affect the innate immune response, these variants account for only a portion of the ability of the host to respond to bacteria, fungi, and viruses. To identify other genes involved in the innate immune response, we challenged 16 inbred murine strains with lipopolysaccharide (LPS) systemically and measured serum concentrations of pro-inflammatory cytokines IL-1beta, IL-6, and TNFalpha, and the chemokine KC 6 hr post-treatment. Loci that segregate with strain phenotypes were identified by whole genome association (WGA) mapping of cytokine concentrations. Published gene expression profiles and quantitative trait loci (QTL) were then utilized to prioritize loci and genes that potentially regulate the host response to LPS. Sixteen loci were selected for further investigation by combining WGA analysis with previously published QTL for murine response to LPS or gram negative bacteria. Thirty-eight genes within these loci were then selected for further investigation on the basis of the significance of the identified locus, transcriptional response to LPS, and biological plausibility. RNA interference-mediated inhibition of 4 of 38 candidate genes was shown to block the production of IL-6 in J774A.1 macrophages. In summary, our analysis identified 4 genes that have not previously been implicated in innate immunity, namely, 1110058L19Rik, 4933415F23Rik, Fbxo9, and Ipo7. These genes could represent potential sepsis biomarkers or therapeutic targets that should be further investigated in human populations.", "author" : [ { "dropping-particle" : "V", "family" : "Yang", "given" : "Ivana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wade", "given" : "Claire M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Hyun Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alper", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rutledge", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lackford", "given" : "Brad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eskin", "given" : "Eleazar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwartz", "given" : "David A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "12", "1" ] ] }, "page" : "1535-44", "title" : "Identification of novel genes that mediate innate immunity using inbred mice.", "type" : "article-journal", "volume" : "183" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "110", "plainTextFormattedCitation" : "110", "previouslyFormattedCitation" : "110" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }110. Additionally, the G risk allele for SGCG rs9552911 is not present in white Caucasians. The putative existence of polymorphisms existing in South Asians that are not present in Caucasians is supported by presence of assortative mating resulting from prolonged geographical and cultural isolation of this region from European whitesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajhg.2013.07.006", "ISSN" : "1537-6605", "PMID" : "23932107", "abstract" : "Most Indian groups descend from a mixture of two genetically divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians (ASI) not closely related to groups outside the subcontinent. The date of mixture is unknown but has implications for understanding Indian history. We report genome-wide data from 73 groups from the Indian subcontinent and analyze linkage disequilibrium to estimate ANI-ASI mixture dates ranging from about 1,900 to 4,200 years ago. In a subset of groups, 100% of the mixture is consistent with having occurred during this period. These results show that India experienced a demographic transformation several thousand years ago, from a region in which major population mixture was common to one in which mixture even between closely related groups became rare because of a shift to endogamy.", "author" : [ { "dropping-particle" : "", "family" : "Moorjani", "given" : "Priya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lipson", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Po-Ru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Govindaraj", "given" : "Periyasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Bonnie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "9", "5" ] ] }, "page" : "422-38", "title" : "Genetic evidence for recent population mixture in India.", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "21", "plainTextFormattedCitation" : "21", "previouslyFormattedCitation" : "21" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }21 as well as founder effectsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nature08365", "ISSN" : "1476-4687", "PMID" : "19779445", "abstract" : "India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' (ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.", "author" : [ { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "7263", "issued" : { "date-parts" : [ [ "2009", "9", "24" ] ] }, "page" : "489-94", "title" : "Reconstructing Indian population history.", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "20", "plainTextFormattedCitation" : "20", "previouslyFormattedCitation" : "20" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20. Non-association of the remaining seven dimorphic SNPs with type 2 diabetes in white Caucasians is quite puzzling as the risk alleles are present in this group. DIAGRAM’s large sample ensures reasonable power; for the lowest RAF of all eight SNPs, DIAGRAM sample had greater than 80% power to detect an OR of at least 1.07, and therefore non-association may be due to substantially different LD structures or lower effect sizes in white Caucasians because of ethnic specific gene–environment or gene–gene interactions. We compared the LD structure for the seven SNPs using HapMap data, and while not substantial, r2 values with neighbouring SNPs have some differences (for example, r2 of rs1048886 with neighbouring rs9455158 is 0.75 in white Caucasians and 0.87 in South Asians; r2 of rs3923113 with neighbouring rs13432797 is 0.93 in white Caucasians and 0.64 in South Asians). We also compared D’ values since r2 tends to depend heavily on allele frequenciesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.tpb.2008.05.006", "ISSN" : "1096-0325", "PMID" : "18572214", "abstract" : "Statistics for linkage disequilibrium (LD), the non-random association of alleles at two loci, depend on the frequencies of the alleles at the loci under consideration. Here, we examine the r(2) measure of LD and its mathematical relationship to allele frequencies, quantifying the constraints on its maximum value. Assuming independent uniform distributions for the allele frequencies of two biallelic loci, we find that the mean maximum value of r(2) is approximately 0.43051, and that r(2) can exceed a threshold of 4/5 in only approximately 14.232% of the allele frequency space. If one locus is assumed to have known allele frequencies--the situation in an association study in which LD between a known marker locus and an unknown trait locus is of interest--we find that the mean maximum value of r(2) is greatest when the known locus has a minor allele frequency of approximately 0.30131. We find that in 1/4 of the space of allowed values of minor allele frequencies and haplotype frequencies at a pair of loci, the unconstrained maximum r(2) allowing for the possibility of recombination between the loci exceeds the constrained maximum assuming that no recombination has occurred. Finally, we use r(max)(2) to examine the connection between r(2) and the D(') measure of linkage disequilibrium, finding that r(2)/r(max)(2)=D('2) for approximately 72.683% of the space of allowed values of (p(a),p(b),p(ab)). Our results concerning the properties of r(2) have the potential to inform the interpretation of unusual LD behavior and to assist in the design of LD-based association-mapping studies.", "author" : [ { "dropping-particle" : "", "family" : "VanLiere", "given" : "Jenna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenberg", "given" : "Noah A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Theoretical population biology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "130-7", "title" : "Mathematical properties of the r2 measure of linkage disequilibrium.", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "111", "plainTextFormattedCitation" : "111", "previouslyFormattedCitation" : "111" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }111. Fine mapping analyses will determine whether the same functional variants are responsible for increased risk in both groups and if the effect is comparable, or if the seven SNPs tag unique functional variants in South Asians.2.4.4 Population burdenNo difference in genotype score between South Asians and white Caucasians was observed, which is consistent with our finding that no trend exists for variation in RAFs. It should be noted that our conclusion is based on an assumption of homogeneity in effect sizes between the groups, supported by our primary analysis. Our conclusion is not consistent with some literature, which shows a greater population burden in South Asians based on unweighted genotype scores ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc12-2553", "ISSN" : "1935-5548", "PMID" : "23603917", "abstract" : "OBJECTIVE: To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.\n\nRESEARCH DESIGN AND METHODS: In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.\n\nRESULTS: Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).\n\nCONCLUSIONS: T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Changchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xiaohe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Jackie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keavney", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudet", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "2836-42", "title" : "Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0024710", "ISSN" : "1932-6203", "PMID" : "21949744", "abstract" : "BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed \u03b2 values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (\u03b2\u200a=\u200a0.063 [95% CI: 0.013, 0.113] p\u200a=\u200a0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative \u03b2 value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p\u200a=\u200a1.29\u00d710(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p\u200a=\u200a9.1\u00d710(-4)) and 1.16 (95% CI: 1.05, 1.29; p\u200a=\u200a3.49\u00d710(-3)) respectively.\n\nCONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e24710", "publisher" : "Public Library of Science", "title" : "Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62,112", "plainTextFormattedCitation" : "62,112", "previouslyFormattedCitation" : "62,112" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62,11233,72ref)e exception of Table 1 at baseline.sing data from the DREAM randomized control trial. Areduced ls was claculated cise . However, while the cumulative genotype score for South Asians was statistically higher than white Caucasians in the referenced study, the magnitude of the difference is small (0.99 points on a scale that varied from 0 to 32)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc12-2553", "ISSN" : "1935-5548", "PMID" : "23603917", "abstract" : "OBJECTIVE: To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.\n\nRESEARCH DESIGN AND METHODS: In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.\n\nRESULTS: Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).\n\nCONCLUSIONS: T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Changchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xiaohe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Jackie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keavney", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudet", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "2836-42", "title" : "Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "62" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62. Moreover, unweighted scores consider the contribution from SNPs with larger effects to be the same as that from SNPs with small effects, and appear to discriminate less effectively between disease statesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1182/blood-2011-12-397752", "ISSN" : "1528-0020", "PMID" : "22586183", "abstract" : "There are no risk models available yet that accurately predict a person's risk for developing venous thrombosis. Our aim was therefore to explore whether inclusion of established thrombosis-associated single nucleotide polymorphisms (SNPs) in a venous thrombosis risk model improves the risk prediction. We calculated genetic risk scores by counting risk-increasing alleles from 31 venous thrombosis-associated SNPs for subjects of a large case-control study, including 2712 patients and 4634 controls (Multiple Environmental and Genetic Assessment). Genetic risk scores based on all 31 SNPs or on the 5 most strongly associated SNPs performed similarly (areas under receiver-operating characteristic curves [AUCs] of 0.70 and 0.69, respectively). For the 5-SNP risk score, the odds ratios for venous thrombosis ranged from 0.37 (95% confidence interval [CI], 0.25-0.53) for persons with 0 risk alleles to 7.48 (95% CI, 4.49-12.46) for persons with more than or equal to 6 risk alleles. The AUC of a risk model based on known nongenetic risk factors was 0.77 (95% CI, 0.76-0.78). Combining the nongenetic and genetic risk models improved the AUC to 0.82 (95% CI, 0.81-0.83), indicating good diagnostic accuracy. To become clinically useful, subgroups of high-risk persons must be identified in whom genetic profiling will also be cost-effective.", "author" : [ { "dropping-particle" : "", "family" : "Haan", "given" : "Hugoline G", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bezemer", "given" : "Irene D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doggen", "given" : "Carine J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cessie", "given" : "Saskia", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reitsma", "given" : "Pieter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arellano", "given" : "Andre R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tong", "given" : "Carmen H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devlin", "given" : "James J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bare", "given" : "Lance A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosendaal", "given" : "Frits R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vossen", "given" : "Carla Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Blood", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "7", "19" ] ] }, "page" : "656-63", "title" : "Multiple SNP testing improves risk prediction of first venous thrombosis.", "type" : "article-journal", "volume" : "120" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/dc11-0957", "ISSN" : "1935-5548", "PMID" : "22275441", "abstract" : "OBJECTIVE: Multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) susceptibility have been identified in predominantly European-derived populations. These SNPs have not been extensively investigated for individual and cumulative effects on T2D risk in African Americans.\n\nRESEARCH DESIGN AND METHODS: Seventeen index T2D risk variants were genotyped in 2,652 African American case subjects with T2D and 1,393 nondiabetic control subjects. Individual SNPs and cumulative risk allele loads were assessed for association with risk for T2D. Cumulative risk was assessed by counting risk alleles and evaluating the difference in cumulative risk scores between case subjects and control subjects. A second analysis weighted risk scores (ln [OR]) based on previously reported European-derived effect sizes.\n\nRESULTS: Frequencies of risk alleles ranged from 8.6 to 99.9%. Eleven SNPs had ORs >1, and 5 from ADAMTS9, WFS1, CDKAL1, JAZF1, and TCF7L2 trended or had nominally significant evidence of T2D association (P < 0.05). Individuals carried between 13 and 29 risk alleles. Association was observed between T2D and increase in risk allele load (unweighted OR 1.04 [95% CI 1.01-1.08], P = 0.010; weighted 1.06 [1.03-1.10], P = 8.10 \u00d7 10(-5)). When TCF7L2 SNP rs7903146 was included as a covariate, the risk score was no longer associated with T2D in either model (unweighted 1.02 [0.98-1.05], P = 0.33; weighted 1.02 [0.98-1.06], P = 0.40).\n\nCONCLUSIONS: The trend of increase in risk for T2D with increasing risk allele load is similar to observations in European-derived populations; however, these analyses indicate that T2D genetic risk is primarily mediated through the effect of TCF7L2 in African Americans.", "author" : [ { "dropping-particle" : "", "family" : "Cooke", "given" : "Jessica N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Maggie C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Nicholette D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "S Sandy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hester", "given" : "Jessica M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freedman", "given" : "Barry I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langefeld", "given" : "Carl D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowden", "given" : "Donald W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "2", "1" ] ] }, "page" : "287-92", "title" : "Genetic risk assessment of type 2 diabetes-associated polymorphisms in African Americans.", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0019454", "ISSN" : "1932-6203", "PMID" : "21559375", "abstract" : "Psoriasis is a chronic, immune-mediated skin disease affecting 2-3% of Caucasians. Recent genetic association studies have identified multiple psoriasis risk loci; however, most of these loci contribute only modestly to disease risk. In this study, we investigated whether a genetic risk score (GRS) combining multiple loci could improve psoriasis prediction. Two approaches were used: a simple risk alleles count (cGRS) and a weighted (wGRS) approach. Ten psoriasis risk SNPs were genotyped in 2815 case-control samples and 858 family samples. We found that the total number of risk alleles in the cases was significantly higher than in controls, mean 13.16 (SD 1.7) versus 12.09 (SD 1.8), p\u200a=\u200a4.577\u00d710(-40). The wGRS captured considerably more risk than any SNP considered alone, with a psoriasis OR for high-low wGRS quartiles of 10.55 (95% CI 7.63-14.57), p\u200a=\u200a2.010\u00d710(-65). To compare the discriminatory ability of the GRS models, receiver operating characteristic curves were used to calculate the area under the curve (AUC). The AUC for wGRS was significantly greater than for cGRS (72.0% versus 66.5%, p\u200a=\u200a2.13\u00d710(-8)). Additionally, the AUC for HLA-C alone (rs10484554) was equivalent to the AUC for all nine other risk loci combined (66.2% versus 63.8%, p\u200a=\u200a0.18), highlighting the dominance of HLA-C as a risk locus. Logistic regression revealed that the wGRS was significantly associated with two subphenotypes of psoriasis, age of onset (p\u200a=\u200a4.91\u00d710(-6)) and family history (p\u200a=\u200a0.020). Using a liability threshold model, we estimated that the 10 risk loci account for only 11.6% of the genetic variance in psoriasis. In summary, we found that a GRS combining 10 psoriasis risk loci captured significantly more risk than any individual SNP and was associated with early onset of disease and a positive family history. Notably, only a small fraction of psoriasis heritability is captured by the common risk variants identified to date.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Haoyan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poon", "given" : "Annie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yeung", "given" : "Celestine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Helms", "given" : "Cynthia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pons", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowcock", "given" : "Anne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwok", "given" : "Pui-Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liao", "given" : "Wilson", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Mailund", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e19454", "publisher" : "Public Library of Science", "title" : "A genetic risk score combining ten psoriasis risk loci improves disease prediction.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1007/s00125-008-1254-y", "ISSN" : "1432-0428", "PMID" : "19139842", "abstract" : "AIMS/HYPOTHESIS: Several susceptibility genes for type 2 diabetes have been discovered recently. Individually, these genes increase the disease risk only minimally. The goals of the present study were to determine, at the population level, the risk of diabetes in individuals who carry risk alleles within several susceptibility genes for the disease and the added value of this genetic information over the clinical predictors.\n\nMETHODS: We constructed an additive genetic score using the most replicated single-nucleotide polymorphisms (SNPs) within 15 type 2 diabetes-susceptibility genes, weighting each SNP with its reported effect. We tested this score in the extensively phenotyped population-based cross-sectional CoLaus Study in Lausanne, Switzerland (n = 5,360), involving 356 diabetic individuals.\n\nRESULTS: The clinical predictors of prevalent diabetes were age, BMI, family history of diabetes, WHR, and triacylglycerol/HDL-cholesterol ratio. After adjustment for these variables, the risk of diabetes was 2.7 (95% CI 1.8-4.0, p = 0.000006) for individuals with a genetic score within the top quintile, compared with the bottom quintile. Adding the genetic score to the clinical covariates improved the area under the receiver operating characteristic curve slightly (from 0.86 to 0.87), yet significantly (p = 0.002). BMI was similar in these two extreme quintiles.\n\nCONCLUSIONS/INTERPRETATION: In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited.", "author" : [ { "dropping-particle" : "", "family" : "Lin", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yuan", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abderrahmani", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirnadel", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sundseth", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lai", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burns", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Middleton", "given" : "L T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roses", "given" : "A D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cardon", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "D M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "600-8", "title" : "Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "113\u2013116", "plainTextFormattedCitation" : "113\u2013116", "previouslyFormattedCitation" : "113\u2013116" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }113–116. It should be noted, though, that the genotype score calculation in the referenced paper is much more direct than ours as it is based on primary data.2.4.5 Strengths and limitationsThis is the first meta-analysis that compares genetic risk of type 2 diabetes in South Asians and white Caucasians. Potential limitations of our study include use of unadjusted allelic OR, which precluded us from accounting for SNP–type 2 diabetes associations altered by adiposity. Use of unadjusted allelic OR depended largely on the unavailability of appropriately adjusted data. However, we informally compared adjusted estimates reported in the study with our unadjusted allelic OR and found the adjustment to make little difference; for example, the OR for GCKR rs780094 in the primary reportADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0024710", "ISSN" : "1932-6203", "PMID" : "21949744", "abstract" : "BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed \u03b2 values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (\u03b2\u200a=\u200a0.063 [95% CI: 0.013, 0.113] p\u200a=\u200a0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative \u03b2 value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p\u200a=\u200a1.29\u00d710(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p\u200a=\u200a9.1\u00d710(-4)) and 1.16 (95% CI: 1.05, 1.29; p\u200a=\u200a3.49\u00d710(-3)) respectively.\n\nCONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e24710", "publisher" : "Public Library of Science", "title" : "Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "112", "plainTextFormattedCitation" : "112", "previouslyFormattedCitation" : "112" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }112 was 0.87 (0.72-1.05) after adjustment for age and sex. In our study, the OR is 0.86 (0.65-1.13). Furthermore, by using allelic OR, we assume an additive model of inheritance, which may not apply to some loci. Second, publication and time-lag biases may exist whereby significant results are published more often than negative studies. To minimise these biases, we conducted a thorough search of literature and consulted experts to identify as many eligible studies as possible. We were unable to produce funnel plots to formally assess publication bias because fewer than ten studies were used to meta-analyse a majority of SNPs. Third, some SNPs in this meta-analysis were only investigated in two cohorts and their summary estimates should be interpreted with caution. Fourth, sample sizes varied with each SNP in South Asians but were consistent for all SNPs in white Caucasians, which may create artificial differences between the groups as a result of differences in precision. Lastly, meta-analyses of candidate gene studies face the same limitations as individual such studies, including improper assessment of population structure and inability to apply stringent multiple testing control to circumvent false-discoveries, among othersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s12863-015-0211-2", "ISSN" : "1471-2156", "PMID" : "25975208", "abstract" : "BACKGROUND: Advances in genomics technology have led to a dramatic increase in the number of published genetic association studies. Systematic reviews and meta-analyses are a common method of synthesizing findings and providing reliable estimates of the effect of a genetic variant on a trait of interest. However, summary estimates are subject to bias due to the varying methodological quality of individual studies. We embarked on an effort to develop and evaluate a tool that assesses the quality of published genetic association studies. Performance characteristics (i.e. validity, reliability, and item discrimination) were evaluated using a sample of thirty studies randomly selected from a previously conducted systematic review.\n\nRESULTS: The tool demonstrates excellent psychometric properties and generates a quality score for each study with corresponding ratings of 'low', 'moderate', or 'high' quality. We applied our tool to a published systematic review to exclude studies of low quality, and found a decrease in heterogeneity and an increase in precision of summary estimates.\n\nCONCLUSION: This tool can be used in systematic reviews to inform the selection of studies for inclusion, to conduct sensitivity analyses, and to perform meta-regressions.", "author" : [ { "dropping-particle" : "", "family" : "Sohani", "given" : "Zahra N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Russell J", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joseph", "given" : "Philip G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gandhi", "given" : "Mandark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dennis", "given" : "Brittany B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norman", "given" : "Geoff", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "1" ] ] }, "page" : "50", "title" : "Assessing the quality of published genetic association studies in meta-analyses: the quality of genetic studies (Q-Genie) tool.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ijo.2012.82", "ISSN" : "1476-5497", "PMID" : "22584455", "abstract" : "A robust replication of initial genetic association findings has proved to be difficult in human complex diseases and more specifically in the obesity field. An obvious cause of non-replication in genetic association studies is the initial report of a false positive result, which can be explained by a non-heritable phenotype, insufficient sample size, improper correction for multiple testing, population stratification, technical biases, insufficient quality control or inappropriate statistical analyses. Replication may, however, be challenging even when the original study describes a true positive association. The reasons include underpowered replication samples, gene \u00d7 gene, gene \u00d7 environment interactions, genetic and phenotypic heterogeneity and subjective interpretation of data. In this review, we address classic pitfalls in genetic association studies and provide guidelines for proper discovery and replication genetic association studies with a specific focus on obesity.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of obesity (2005)", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "4" ] ] }, "page" : "559-67", "title" : "Challenges in reproducibility of genetic association studies: lessons learned from the obesity field.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2174/1573400510666140630170549", "ISSN" : "1573-4005", "PMID" : "25598768", "abstract" : "The rapid decline of sequencing costs brings hope that personal genome sequencing will become a common feature of medical practice. This series of three reviews aim to help non-geneticist clinicians to jump into the fast-moving field of personalized genetic medicine. In the first two articles, we covered the fundamental concepts of molecular genetics and the methodologies used in genetic epidemiology. In this third article, we discuss the evolution of personalized medicine and illustrate the most recent success in the fields of Mendelian and complex human diseases. We also address the challenges that currently limit the use of personalized medicine to its full potential.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "Aihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current psychiatry reviews", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "118-132", "title" : "Jumping on the Train of Personalized Medicine: A Primer for Non- Geneticist Clinicians: Part 3. Clinical Applications in the Personalized Medicine Area.", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "117\u2013119", "plainTextFormattedCitation" : "117\u2013119", "previouslyFormattedCitation" : "117\u2013119" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }117–119. Our conclusions regarding the genetic heterogeneity between South Asians and white Caucasians are applicable only to genetic risk from bi-allelic common SNPs as our investigation was limited to this type of variant.2.4.6 Future directionsThe question of why South Asians have a greater risk for type 2 diabetes remains unanswered from a genetic perspective as risk from common SNPs predisposing to type 2 diabetes does not differ. Our results are particularly important as they emphasise the need for future research to explore ethnic-specific heritable epigenetic changes, epistasis and gene–environment interactions, homozygocity mapping in consanguineous pedigrees, as well as exome-sequencing to answer this questionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/456018a", "ISSN" : "1476-4687", "PMID" : "18987709", "author" : [ { "dropping-particle" : "", "family" : "Maher", "given" : "Brendan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "7218", "issued" : { "date-parts" : [ [ "2008", "11", "6" ] ] }, "page" : "18-21", "title" : "Personal genomes: The case of the missing heritability.", "type" : "article-journal", "volume" : "456" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/nature08494", "ISSN" : "1476-4687", "PMID" : "19812666", "abstract" : "Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.", "author" : [ { "dropping-particle" : "", "family" : "Manolio", "given" : "Teri A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Nancy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldstein", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hindorff", "given" : "Lucia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramos", "given" : "Erin M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cardon", "given" : "Lon R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakravarti", "given" : "Aravinda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Judy H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guttmacher", "given" : "Alan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruglyak", "given" : "Leonid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mardis", "given" : "Elaine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotimi", "given" : "Charles N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slatkin", "given" : "Montgomery", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whittemore", "given" : "Alice S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clark", "given" : "Andrew G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eichler", "given" : "Evan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gibson", "given" : "Greg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haines", "given" : "Jonathan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mackay", "given" : "Trudy F C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visscher", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-2", "issue" : "7265", "issued" : { "date-parts" : [ [ "2009", "10", "8" ] ] }, "page" : "747-53", "title" : "Finding the missing heritability of complex diseases.", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "14,15", "plainTextFormattedCitation" : "14,15", "previouslyFormattedCitation" : "14,15" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }14,15, rather than focusing on exploring differences in risk estimates and RAFs. Additionally, differences in genetic risk may result from low-frequency causal variants with large effects (rare variants)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrg2779", "ISSN" : "1471-0064", "PMID" : "20479773", "abstract" : "Although genome-wide association (GWA) studies for common variants have thus far succeeded in explaining only a modest fraction of the genetic components of human common diseases, recent advances in next-generation sequencing technologies could rapidly facilitate substantial progress. This outcome is expected if much of the missing genetic control is due to gene variants that are too rare to be picked up by GWA studies and have relatively large effects on risk. Here, we evaluate the evidence for an important role of rare gene variants of major effect in common diseases and outline discovery strategies for their identification.", "author" : [ { "dropping-particle" : "", "family" : "Cirulli", "given" : "Elizabeth T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldstein", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Genetics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2010", "6" ] ] }, "page" : "415-25", "title" : "Uncovering the roles of rare variants in common disease through whole-genome sequencing.", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pbio.1000579", "ISSN" : "1545-7885", "PMID" : "21267061", "author" : [ { "dropping-particle" : "", "family" : "Wray", "given" : "Naomi R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purcell", "given" : "Shaun M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visscher", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS biology", "editor" : [ { "dropping-particle" : "", "family" : "Flint", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e1000579", "publisher" : "Public Library of Science", "title" : "Synthetic associations created by rare variants do not explain most GWAS results.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "120,121", "plainTextFormattedCitation" : "120,121", "previouslyFormattedCitation" : "120,121" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }120,121. In fact, there has been recent evidence supporting the existence of rare ethnic specific exonic variants associated with type 2 diabetesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nature12828", "ISSN" : "1476-4687", "PMID" : "24390345", "abstract" : "Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 \u00d7 10(-13); odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 \u00d7 10(-4); OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ~50% frequency in Native American samples and ~10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.", "author" : [ { "dropping-particle" : "", "family" : "Williams", "given" : "Amy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Suzanne B R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreno-Mac\u00edas", "given" : "Hortensia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huerta-Chagoya", "given" : "Alicia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Churchhouse", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e1rquez-Luna", "given" : "Carla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Ort\u00edz", "given" : "Humberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f3mez-V\u00e1zquez", "given" : "Mar\u00eda Jos\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aguilar-Salinas", "given" : "Carlos A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Villalpando", "given" : "Clicerio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orozco", "given" : "Lorena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haiman", "given" : "Christopher A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tusi\u00e9-Luna", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "7486", "issued" : { "date-parts" : [ [ "2014", "2", "6" ] ] }, "page" : "97-101", "title" : "Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico.", "type" : "article-journal", "volume" : "506" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1001/jama.2014.6511", "ISSN" : "1538-3598", "PMID" : "24915262", "abstract" : "IMPORTANCE: Latino populations have one of the highest prevalences of type 2 diabetes worldwide.\n\nOBJECTIVES: To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships.\n\nDESIGN, SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013. One variant was further tested for allele frequency and association with type 2 diabetes in large multiethnic data sets of 14,276 participants and characterized in experimental assays.\n\nMAIN OUTCOME AND MEASURES: Prevalence of type 2 diabetes. Secondary outcomes included age of onset, body mass index, and effect on protein function.\n\nRESULTS: A single rare missense variant (c.1522G>A [p.E508K]) was associated with type 2 diabetes prevalence (odds ratio [OR], 5.48; 95% CI, 2.83-10.61; P = 4.4 \u00d7 10(-7)) in hepatocyte nuclear factor 1-\u03b1 (HNF1A), the gene responsible for maturity onset diabetes of the young type 3 (MODY3). This variant was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it. In multiethnic replication data sets, the p.E508K variant was seen only in Latino patients (n = 1443 with type 2 diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16; 95% CI, 1.75-9.92; P =\u2009.0013). In experimental assays, HNF-1A protein encoding the p.E508K mutant demonstrated reduced transactivation activity of its target promoter compared with a wild-type protein. In our data, carriers and noncarriers of the p.E508K mutation with type 2 diabetes had no significant differences in compared clinical characteristics, including age at onset. The mean (SD) age for carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P =\u2009.49) and the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P =\u2009.19).\n\nCONCLUSIONS AND RELEVANCE: Using whole-exome sequencing, we identified a single low-frequency variant in the MODY3-causing gene HNF1A that is associated with type 2 diabetes in Latino populations and may affect protein function. This finding may have implications for screening and therapeutic modification in this population, but additional studies are required.", "author" : [ { "dropping-particle" : "", "family" : "Estrada", "given" : "Karol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aukrust", "given" : "Ingvild", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bj\u00f8rkhaug", "given" : "Lise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "No\u00ebl P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mercader", "given" : "Josep M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Ortiz", "given" : "Humberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huerta-Chagoya", "given" : "Alicia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreno-Mac\u00edas", "given" : "Hortensia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walford", "given" : "Geoffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flannick", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Amy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "G\u00f3mez-V\u00e1zquez", "given" : "Mar\u00eda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fernandez-Lopez", "given" : "Juan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Hern\u00e1ndez", "given" : "Ang\u00e9lica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez-Morales", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Centeno-Cruz", "given" : "Federico", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mendoza-Caamal", "given" : "Elvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Revilla-Monsalve", "given" : "Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islas-Andrade", "given" : "Sergio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "C\u00f3rdova", "given" : "Emilio J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sober\u00f3n", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Villalpando", "given" : "Mar\u00eda E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilkens", "given" : "Lynne R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchand", "given" : "Loic", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arellano-Campos", "given" : "Olimpia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ord\u00f3\u00f1ez-S\u00e1nchez", "given" : "Maria L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodr\u00edguez-Torres", "given" : "Maribel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodr\u00edguez-Guill\u00e9n", "given" : "Rosario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riba", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Najmi", "given" : "Laeya A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Suzanne B R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fennell", "given" : "Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabriel", "given" : "Stacey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontanillas", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanis", "given" : "Craig L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehman", "given" : "Donna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jenkinson", "given" : "Christopher P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abboud", "given" : "Hanna E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "Graeme I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cortes", "given" : "Maria L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Villalpando", "given" : "Clicerio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orozco", "given" : "Lorena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haiman", "given" : "Christopher A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tusi\u00e9-Luna", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aguilar-Salinas", "given" : "Carlos A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nj\u00f8lstad", "given" : "P\u00e5l R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "MacArthur", "given" : "Daniel G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA", "id" : "ITEM-2", "issue" : "22", "issued" : { "date-parts" : [ [ "2014", "6", "11" ] ] }, "page" : "2305-14", "title" : "Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population.", "type" : "article-journal", "volume" : "311" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/nature13425", "ISSN" : "1476-4687", "PMID" : "25043022", "abstract" : "The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during the past 25 years. Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%. Here we show that homozygous carriers of this variant have markedly higher concentrations of plasma glucose (\u03b2 = 3.8\u2009mmol\u2009l(-1), P = 2.5\u2009\u00d7\u200910(-35)) and serum insulin (\u03b2 = 165\u2009pmol\u2009l(-1), P = 1.5\u2009\u00d7\u200910(-20)) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (\u03b2 = -0.18 mmol\u2009l(-1), P = 1.1\u2009\u00d7\u200910(-6)) and fasting serum insulin (\u03b2 = -8.3\u2009pmol\u2009l(-1), P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6\u2009\u00d7\u200910(-24)). Heterozygous carriers have a moderately higher plasma glucose concentration 2 hours after an oral glucose load than non-carriers (\u03b2 = 0.43\u2009mmol\u2009l(-1), P = 5.3\u2009\u00d7\u200910(-5)). Analyses of skeletal muscle biopsies showed lower messenger RNA and protein levels of the long isoform of TBC1D4, and lower muscle protein levels of the glucose transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any previous findings in large-scale genome-wide association studies of these traits and constitute further proof of the value of conducting genetic association studies outside the traditional setting of large homogeneous populations.", "author" : [ { "dropping-particle" : "", "family" : "Moltke", "given" : "Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Marit E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjerregaard", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treebak", "given" : "Jonas T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fumagalli", "given" : "Matteo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korneliussen", "given" : "Thorfinn S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Marianne A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krarup", "given" : "Nikolaj T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gjesing", "given" : "Anette P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zierath", "given" : "Juleen R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linneberg", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Xueli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Guangqing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jin", "given" : "Xin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Aama", "given" : "Jumana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nielsen", "given" : "Rasmus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albrechtsen", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-3", "issue" : "7513", "issued" : { "date-parts" : [ [ "2014", "8", "14" ] ] }, "page" : "190-3", "title" : "A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes.", "type" : "article-journal", "volume" : "512" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "122\u2013124", "plainTextFormattedCitation" : "122\u2013124", "previouslyFormattedCitation" : "122\u2013124" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }122–124 The existence of such rare variants can be investigated through candidate gene, whole-genome or whole-exome sequencing. In fact, discovery of rare variants for Crohn’s disease greatly supports this paradigmADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/35079107", "ISSN" : "0028-0836", "PMID" : "11385576", "abstract" : "Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.", "author" : [ { "dropping-particle" : "", "family" : "Hugot", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chamaillard", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zouali", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lesage", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "C\u00e9zard", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belaiche", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almer", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tysk", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Morain", "given" : "C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gassull", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Binder", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finkel", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cortot", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Modigliani", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laurent-Puig", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gower-Rousseau", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Macry", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colombel", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sahbatou", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "6837", "issued" : { "date-parts" : [ [ "2001", "5", "31" ] ] }, "page" : "599-603", "publisher" : "Macmillian Magazines Ltd.", "title" : "Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.", "title-short" : "Nature", "type" : "article-journal", "volume" : "411" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "125", "plainTextFormattedCitation" : "125", "previouslyFormattedCitation" : "125" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }125. Large-scale exon resequencing around an MTNR1B SNP modestly associated with type 2 diabetes (OR between 1.10 and 1.15) identified four rare variants that led to loss of melatonin binding and signalling capacity (OR 5.67, 95% CI 2.17-14.82)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.1053", "ISSN" : "1546-1718", "PMID" : "22286214", "abstract" : "Genome-wide association studies have revealed that common noncoding variants in MTNR1B (encoding melatonin receptor 1B, also known as MT(2)) increase type 2 diabetes (T2D) risk(1,2). Although the strongest association signal was highly significant (P < 1 \u00d7 10(-20)), its contribution to T2D risk was modest (odds ratio (OR) of \u223c1.10-1.15)(1-3). We performed large-scale exon resequencing in 7,632 Europeans, including 2,186 individuals with T2D, and identified 40 nonsynonymous variants, including 36 very rare variants (minor allele frequency (MAF) <0.1%), associated with T2D (OR = 3.31, 95% confidence interval (CI) = 1.78-6.18; P = 1.64 \u00d7 10(-4)). A four-tiered functional investigation of all 40 mutants revealed that 14 were non-functional and rare (MAF < 1%), and 4 were very rare with complete loss of melatonin binding and signaling capabilities. Among the very rare variants, the partial- or total-loss-of-function variants but not the neutral ones contributed to T2D (OR = 5.67, CI = 2.17-14.82; P = 4.09 \u00d7 10(-4)). Genotyping the four complete loss-of-function variants in 11,854 additional individuals revealed their association with T2D risk (8,153 individuals with T2D and 10,100 controls; OR = 3.88, CI = 1.49-10.07; P = 5.37 \u00d7 10(-3)). This study establishes a firm functional link between MTNR1B and T2D risk.", "author" : [ { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cl\u00e9ment", "given" : "Nathalie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fawcett", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaillant", "given" : "Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guillaume", "given" : "Jean-Luc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dechaume", "given" : "Aur\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roussel", "given" : "Ronan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czernichow", "given" : "S\u00e9bastien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaxillaire", "given" : "Martine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jockers", "given" : "Ralf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "3" ] ] }, "page" : "297-301", "title" : "Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "126", "plainTextFormattedCitation" : "126", "previouslyFormattedCitation" : "126" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }126. Using a family-based approach with multiple affected members or studying founder populations can facilitate the identification of rare variants in sequencing studies. Last, systematic reviews and primary studies comparing dietary intake and physical activity patterns between South Asians and white Caucasians have noted considerable variationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1079/BJN19970114", "ISSN" : "0007-1145", "author" : [ { "dropping-particle" : "", "family" : "Simmons", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Rhys", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Nutrition", "id" : "ITEM-1", "issue" : "01", "issued" : { "date-parts" : [ [ "2007", "3", "9" ] ] }, "language" : "English", "page" : "5", "publisher" : "Cambridge University Press", "title" : "Dietary practices among Europeans and different South Asian groups in Coventry", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/1479-5868-9-150", "ISSN" : "1479-5868", "PMID" : "23256686", "abstract" : "INTRODUCTION: The objective of this systematic mixed-methods review is to assess what is currently known about the levels of physical activity (PA) and sedentary time (ST) and to contextualize these behaviors among South Asian women with an immigrant background.\n\nMETHODS: A systematic search of the literature was conducted using combinations of the key words PA, ST, South Asian, and immigrant. A mixed-methods approach was used to analyze and synthesize all evidence, both quantitative and qualitative. Twenty-six quantitative and twelve qualitative studies were identified as meeting the inclusion criteria.\n\nRESULTS: Studies quantifying PA and ST among South Asian women showed low levels of PA compared with South Asian men and with white European comparison populations. However making valid comparisons between studies was challenging due to a lack of standardized PA measurement. The majority of studies indicated that South Asian women did not meet recommended amounts of PA for health benefits. Few studies assessed ST. Themes emerging from qualitative studies included cultural and structural barriers to PA, faith and education as facilitators, and a lack of understanding of the recommended amounts of PA and its benefits among South Asian women.\n\nCONCLUSIONS: Quantitative and qualitative evidence indicate that South Asian women do not perform the recommended level of PA for health benefits. Both types of studies suffer from limitations due to methods of data collection. More research should be dedicated to standardizing objective PA measurement and to understanding how to utilize the resources of the individuals and communities to increase PA levels and overall health of South Asian women.", "author" : [ { "dropping-particle" : "", "family" : "Babakus", "given" : "Whitney S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "Janice L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The international journal of behavioral nutrition and physical activity", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "150", "title" : "Physical activity among South Asian women: a systematic, mixed-methods review.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "127,128", "plainTextFormattedCitation" : "127,128", "previouslyFormattedCitation" : "127,128" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }127,128, which may also contribute to the differences observed between the two ethnic groups.2.5 ConclusionsSimilar effect sizes for SNPs predisposing to type 2 diabetes are apparent among South Asians and white Caucasians, but there is variation in RAFs. Additionally, some novel SNPs are present in South Asians. Given the current literature, there is no strong evidence to indicate that currently known genetic variants explain the higher risk of type 2 diabetes in South Asians compared with white Caucasians.Chapter 3Dysglycemia from genetic pancreatic beta-cell failure is worsened by abdominal obesity 3.1 BackgroundIn healthy individuals, glucose tolerance is maintained by insulin secreted from pancreatic beta-cells in response to physiological demands. Blood glucose levels increase when beta-cells fail to respond to these demands or as a result of ineffective action of the secreted insulinADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(05)61032-X", "ISSN" : "1474-547X", "PMID" : "15823385", "abstract" : "Type 2 diabetes mellitus has become an epidemic, and virtually no physician is without patients who have the disease. Whereas insulin insensitivity is an early phenomenon partly related to obesity, pancreas beta-cell function declines gradually over time already before the onset of clinical hyperglycaemia. Several mechanisms have been proposed, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction for insulin resistance, and glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction. Moreover, the disease has a strong genetic component, but only a handful of genes have been identified so far: genes for calpain 10, potassium inward-rectifier 6.2, peroxisome proliferator-activated receptor gamma, insulin receptor substrate-1, and others. Management includes not only diet and exercise, but also combinations of anti-hyperglycaemic drug treatment with lipid-lowering, antihypertensive, and anti platelet therapy.", "author" : [ { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldstein", "given" : "Barry J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haeften", "given" : "Timon W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9467", "issued" : { "date-parts" : [ [ "0" ] ] }, "page" : "1333-46", "title" : "Type 2 diabetes: principles of pathogenesis and therapy.", "type" : "article-journal", "volume" : "365" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/edrv.19.4.0338", "ISSN" : "0163-769X", "PMID" : "9715377", "abstract" : "Despite the fact that it is the prevalent view that insulin resistance is the main genetic factor predisposing to development of type 2 diabetes, review of several lines of evidence in the literature indicates a lack of overwhelming support for this concept. In fact, the literature better supports the case of impaired insulin secretion being the initial and main genetic factor predisposing to type 2 diabetes, especially 1) the studies in people at high risk to subsequently develop type 2 diabetes (discordant monozygotic twins and women with previous gestational diabetes), 2) the studies demonstrating compete alleviation of insulin resistance with weight loss, and 3) the studies finding that people with type 2 diabetes or IGT can have impaired insulin secretion and no insulin resistance compared with well matched NGT subjects. The fact that insulin resistance may be largely an acquired problem in no way lessens its importance in the pathogenesis of type 2 diabetes. Life style changes (exercise, weight reduction) and pharmacological agents (e.g., biguanides and thiazolidendiones) that reduce insulin resistance or increase insulin sensitivity clearly have major beneficial effects (122, 144-146, 153-155).", "author" : [ { "dropping-particle" : "", "family" : "Gerich", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrine reviews", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "1998", "8" ] ] }, "page" : "491-503", "title" : "The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/S0168-8227(11)70015-8", "ISSN" : "1872-8227", "PMID" : "21864753", "abstract" : "In the natural history of type 2 diabetes (T2DM), individuals progress from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to overt T2DM and this progression has been demonstrated in populations of diverse ethnic background. It is widely recognised that both insulin resistance and beta-cell dysfunction are important in the pathogenesis of glucose intolerance. In populations with a high prevalence of T2DM, insulin resistance is well established long before the development of any impairment in glucose homeostasis, particularly in subjects with ectopic fat accumulation. However, as long as the beta cell is able to secrete sufficient amounts of insulin to offset the severity of insulin resistance, glucose tolerance remains normal. This dynamic interaction between insulin secretion and insulin resistance is essential to the maintenance of NGT and interruption of this crosstalk between the beta cell and peripheral tissues results in the progressive deterioration of glucose homeostasis. In this paper the role of beta-cell function is reviewed, as well as the role of ectopic fat accumulation and insulin resistance in the development of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Gastaldelli", "given" : "Amalia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes research and clinical practice", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "S60-5", "title" : "Role of beta-cell dysfunction, ectopic fat accumulation and insulin resistance in the pathogenesis of type 2 diabetes mellitus.", "type" : "article-journal", "volume" : "93 Suppl 1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "2,129,130", "plainTextFormattedCitation" : "2,129,130", "previouslyFormattedCitation" : "2,129,130" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }2,129,130. The resulting elevation in glucose and eventually lipids in turn compromise the beta-cells’ ability to compensate by inhibiting glucose-induced insulin secretion, reducing insulin gene expression, and/or inducing apoptosis of islet cells, a phenomenon known as ‘glucolipotoxicity’ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/er.2007-0023", "ISSN" : "0163-769X", "PMID" : "18048763", "abstract" : "Glucotoxicity, lipotoxicity, and glucolipotoxicity are secondary phenomena that are proposed to play a role in all forms of type 2 diabetes. The underlying concept is that once the primary pathogenesis of diabetes is established, probably involving both genetic and environmental forces, hyperglycemia and very commonly hyperlipidemia ensue and thereafter exert additional damaging or toxic effects on the beta-cell. In addition to their contribution to the deterioration of beta-cell function after the onset of the disease, elevations of plasma fatty acid levels that often accompany insulin resistance may, as glucose levels begin to rise outside of the normal range, also play a pathogenic role in the early stages of the disease. Because hyperglycemia is a prerequisite for lipotoxicity to occur, the term glucolipotoxicity, rather than lipotoxicity, is more appropriate to describe deleterious effects of lipids on beta-cell function. In vitro and in vivo evidence supporting the concept of glucotoxicity is presented first, as well as a description of the underlying mechanisms with an emphasis on the role of oxidative stress. Second, we discuss the functional manifestations of glucolipotoxicity on insulin secretion, insulin gene expression, and beta-cell death, and the role of glucose in the mechanisms of glucolipotoxicity. Finally, we attempt to define the role of these phenomena in the natural history of beta-cell compensation, decompensation, and failure during the course of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Poitout", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "R Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrine reviews", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "351-66", "title" : "Glucolipotoxicity: fuel excess and beta-cell dysfunction.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "131", "plainTextFormattedCitation" : "131", "previouslyFormattedCitation" : "131" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }131.Among South Asians, longitudinal studies of glycemic traits show steeper age-related increases in fasting glucose with lower age-related increases in HOMA2-%BADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-014-3448-9", "ISSN" : "1432-0428", "PMID" : "25431266", "abstract" : "AIMS/HYPOTHESIS: South Asian individuals have an increased prevalence of type 2 diabetes, but little is known about the development of glycaemic traits in this ethnic group. We compared age-related changes in glycaemic traits between non-diabetic South Asian and white participants.\n\nMETHODS: In a prospective British occupational cohort with 5-yearly clinical examinations (n\u2009=\u2009230/5,749 South Asian/white participants, age 39-79\u00a0years at baseline), age-related trajectories of fasting glucose (FG) and 2\u00a0h post-load glucose (PLG), log-transformed fasting insulin (FINS) and 2\u00a0h post-load insulin (PLINS), HOMA insulin sensitivity (HOMA2-%S) and HOMA insulin secretion (HOMA2-%B) were fitted for South Asian and white individuals who remained free of diabetes between 1991 and 2009.\n\nRESULTS: In sex-adjusted multilevel models, FG was stable in white participants but increased with age in South Asians (0.12 [SE\u2009=\u20090.04] mmol/l per decade). PLG, FINS and PLINS levels were lower among white participants (by 0.271 [SE\u2009=\u20090.092] mmol/l, 0.306 [SE\u2009=\u20090.046] log pmol/l, 0.707 [SE\u2009=\u20090.059] log pmol/l at age 50, respectively) compared with South Asians, although their age-related trajectories were parallel. HOMA2-%S was higher (0.226 [SE\u2009=\u20090.038] at age 50) and HOMA2-%B lower (by 0.189 [SE\u2009=\u20090.026] at age 50) among white than South Asian participants. The age-related decline in HOMA2-%S was similar in these groups, but the age-related increase in HOMA2-%B was greater in white participants (0.04 [SE\u2009=\u20090.02] per decade). This difference was explained by obesity, lifestyle and social status.\n\nCONCLUSIONS/INTERPRETATION: Findings from a diabetes-free population suggest an inadequate pancreatic beta cell reserve in South Asians, as a significantly steeper age-related increase in FG was observed in this ethnic group compared with white individuals.", "author" : [ { "dropping-particle" : "", "family" : "Ikehara", "given" : "Satoyo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tab\u00e1k", "given" : "Adam G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akbaraly", "given" : "Tasnime N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hulm\u00e1n", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivim\u00e4ki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iso", "given" : "Hiroyasu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3" ] ] }, "page" : "534-42", "title" : "Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study.", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "32", "plainTextFormattedCitation" : "32", "previouslyFormattedCitation" : "32" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }32, suggesting a comparatively lower beta-cell output than white Caucasians. Yet, the evidence for a greater genetic propensity for beta-cell impairment in this group is inconsistentADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-014-3354-1", "ISSN" : "1432-0428", "PMID" : "25145545", "abstract" : "AIMS/HYPOTHESIS: South Asians are up to four times more likely to develop type 2 diabetes than white Europeans. It is postulated that the higher prevalence results from greater genetic risk. To evaluate this hypothesis, we: (1) systematically reviewed the literature for single nucleotide polymorphisms (SNPs) predisposing to type 2 diabetes in South Asians; (2) compared risk estimates, risk alleles and risk allele frequencies of predisposing SNPs between South Asians and white Europeans; and (3) tested the association of novel SNPs discovered from South Asians in white Europeans.\n\nMETHODS: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane registry were searched for studies of genetic variants associated with type 2 diabetes in South Asians. Meta-analysis estimates for common and novel bi-allelic SNPs in South Asians were compared with white Europeans from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. The population burden from predisposing SNPs was assessed using a genotype score.\n\nRESULTS: Twenty-four SNPs from 21 loci were associated with type 2 diabetes in South Asians after meta-analysis. The majority of SNPs increase odds of the disorder by 15-35% per risk allele. No substantial differences appear to exist in risk estimates between South Asians and white Europeans from SNPs common to both groups, and the population burden also does not differ. Eight of the 24 are novel SNPs discovered from South Asian genome-wide association studies, some of which show nominal associations with type 2 diabetes in white Europeans.\n\nCONCLUSIONS/INTERPRETATION: Based on current literature there is no strong evidence to indicate that South Asians possess a greater genetic risk of type 2 diabetes than white Europeans.", "author" : [ { "dropping-particle" : "", "family" : "Sohani", "given" : "Zahra N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Wei Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014", "8", "22" ] ] }, "title" : "Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.2897", "ISSN" : "1546-1718", "PMID" : "24509480", "abstract" : "To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.", "author" : [ { "dropping-particle" : "", "family" : "DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "South Asian Type 2 Diabetes (SAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mexican American Type 2 Diabetes (MAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Go", "given" : "Min Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Below", "given" : "Jennifer E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horikoshi", "given" : "Momoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Maggie C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adair", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldassarre", "given" : "Damiano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bao", "given" : "Yuqian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "Graeme I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Qiuyin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carey", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "Juliana C N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Li-Ching", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Tien-Jyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yi-Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chien-Hsiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuan-Tsong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Nam H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Young Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chuang", "given" : "Lee-Ming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crenshaw", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donnelly", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorkhan", "given" : "Mozhgan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Josee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edkins", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erbel", "given" : "Raimund", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Escobedo", "given" : "Jorge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esko", "given" : "Tonu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eury", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontanillas", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsen", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraser", "given" : "Ross M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gao", "given" : "Yutang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gertow", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Bok-Ghee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmen", "given" : "Oddgeir L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hovingh", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hreidarsson", "given" : "Astradur B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunt", "given" : "Sarah E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikegami", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jia", "given" : "Weiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jockel", "given" : "Karl-Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Hyun Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen Hong L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "Ann M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Hassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hyung-Lae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Sangsoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Young Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinnunen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korpi-Hyovalti", "given" : "Eeva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kravic", "given" : "Jasmina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krithika", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Ashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumate", "given" : "Jesus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwak", "given" : "Soo Heon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langford", "given" : "Cordelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leander", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jen-Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Nanette R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindholm", "given" : "Eero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jian Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Long", "given" : "Jirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ma", "given" : "Ronald C W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mannisto", "given" : "Satu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metspalu", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mirza", "given" : "Ghazala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mihailov", "given" : "Evelin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moebus", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muhleisen", "given" : "Thomas W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muller-Nurasyid", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musk", "given" : "Bill", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Jiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakashima", "given" : "Eitaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Njolstad", "given" : "Inger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nothen", "given" : "Markus M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohnaka", "given" : "Keizo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Twee Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Kyong Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkin", "given" : "Melissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pechlivanis", "given" : "Sonali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl G P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Jackie F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rallidis", "given" : "Loukianos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossin", "given" : "Elizabeth J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saltevo", "given" : "Juha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saramies", "given" : "Jouko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segre", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shu", "given" : "Xiao Ou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigur[eth]sson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sivapalaratnam", "given" : "Suthesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "So", "given" : "Wing Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stancakova", "given" : "Alena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinbach", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syvanen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takayanagi", "given" : "Ryoichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teslovich", "given" : "Tanya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tikkanen", "given" : "Emmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trakalo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tremoli", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trip", "given" : "Mieke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Fuu Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valladares-Salgado", "given" : "Adan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vedantam", "given" : "Sailaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veglia", "given" : "Fabrizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Congrong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wennauer", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilsgaard", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiltshire", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winckler", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jer-Yuarn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Loic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokota", "given" : "Mitsuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabaneh", "given" : "Delilah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowden", "given" : "Donald W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Nancy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruz", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanis", "given" : "Craig L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jong-Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parra", "given" : "Esteban J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "3" ] ] }, "page" : "234-44", "publisher" : "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.", "title" : "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "104,132", "plainTextFormattedCitation" : "104,132", "previouslyFormattedCitation" : "104,132" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }104,132. Conversely, presence of diminished sensitivity to insulin, after accounting for differences in BMI, among South Asians is well characterizedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0140-6736", "PMID" : "1671422", "abstract" : "The hypothesis that the high mortality from coronary heart disease (CHD) in South Asians settled overseas compared with other populations is due to metabolic disturbances related to insulin resistance was tested in a population survey of 3193 men and 561 women aged 40-69 years in London, UK. The sample was assembled from industrial workforces and general practitioners' lists. In comparison with the European group, the South Asian group had a higher prevalence of diabetes (19% vs 4%), higher blood pressures, higher fasting and post-glucose serum insulin concentrations, higher plasma triglyceride, and lower HDL cholesterol concentrations. Mean waist-hip girth ratios and trunk skinfolds were higher in the South Asian than in the European group. Within each ethnic group waist-hip ratio was correlated with glucose intolerance, insulin, blood pressure, and triglyceride. These results confirm the existence of an insulin resistance syndrome, prevalent in South Asian populations and associated with a pronounced tendency to central obesity in this group. Control of obesity and greater physical activity offer the best chances for prevention of diabetes and CHD in South Asian people.", "author" : [ { "dropping-particle" : "", "family" : "McKeigue", "given" : "P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "M G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "8738", "issued" : { "date-parts" : [ [ "1991", "2", "16" ] ] }, "page" : "382-6", "title" : "Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians.", "type" : "article-journal", "volume" : "337" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jcem.86.11.7992", "ISSN" : "0021-972X", "PMID" : "11701707", "abstract" : "Previous studies have shown that Asian Indians (AIs) are insulin resistant and at high risk for developing diabetes and coronary heart disease, compared with Caucasians. To examine whether differences in body fat distribution contribute to this risk, 12 healthy AIs and 12 Caucasians matched for age and body mass index (BMI) underwent a 75-g oral glucose tolerance test, 2-h euglycemic hyperinsulinemic clamp, abdominal (L2-3) computed tomography scan, and fasting lipid and plasminogen activator inhibitor-1 (PAI-1) levels. Despite similar fasting plasma glucose levels, AIs exhibited fasting hyperinsulinemia (P = 0.001), higher glucose (P = 0.03) and insulin (P = 0.004) levels during the oral glucose tolerance test, and reduced glucose disposal rate (R(d)) (4.7 +/- 0.4 vs. 7.5 +/- 0.3 mg/kg per min, P < 0.0001) during the clamp. AIs had significantly lower high-density lipoprotein, higher low-density lipoprotein, and significantly higher PAI-1 levels (P = 0.01). Despite similar BMI, AIs had significantly greater total abdominal fat (P = 0.04) and visceral fat (P = 0.04). In all subjects, measures of fat mass were inversely correlated with R(d) during the clamp (r = -0.47 to -0.61, P < 0.01-0.001). Visceral fat mass was correlated with triglycerides, low-density lipoprotein, and high-density lipoprotein (P < 0.002-0.0001). PAI-1 was inversely correlated with R(d) in AIs (r = -0.70, P < 0.01) and not in Caucasians (r = -0.24, P = 0.44). For comparable BMI and age, healthy AIs have physiologic markers for insulin resistance, dyslipidemia, and increased cardiovascular risk, compared with Caucasians. Alterations in body fat distribution--particularly increased visceral fat--may contribute to these abnormalities.", "author" : [ { "dropping-particle" : "", "family" : "Raji", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seely", "given" : "E W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arky", "given" : "R A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simonson", "given" : "D C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2001", "11" ] ] }, "page" : "5366-71", "title" : "Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0000812", "ISSN" : "1932-6203", "author" : [ { "dropping-particle" : "", "family" : "Chandalia", "given" : "Manisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seenivasan", "given" : "Thanalakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Livingston", "given" : "Edward H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Snell", "given" : "Peter G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abate", "given" : "Nicola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Maedler", "given" : "Kathrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8", "29" ] ] }, "page" : "e812", "title" : "Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "31,37,133", "plainTextFormattedCitation" : "31,37,133", "previouslyFormattedCitation" : "31,37,133" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }31,37,133. This variation in insulin response may result from South Asians’ tendency to store fat in ectopic regions and the liverADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0022112", "ISSN" : "1932-6203", "PMID" : "21829446", "abstract" : "OBJECTIVE: We sought to determine if differences in the distribution and characteristics of adipose tissue between South Asians and white Caucasians account for differences in risk factors for cardiovascular disease.\n\nRESEARCH DESIGN AND METHODS: We recruited 108 healthy South Asians (36.8 years) and white Caucasians (34.2 years) within three BMI strata. Body composition, adipocyte size, abdominal fat area, and hepatic adiposity were assessed and related to fasting glucose, insulin, lipids and adiponectin.\n\nRESULTS: After adjustment for age, sex, and BMI, South Asians compared to white Caucasians had higher ln fasting insulin (mean difference (MD): 0.44; 95% CI: 0.20-0.69), lower HDL cholesterol (md: -0.13; 95% CI:-0.26 to -0.01), and lower adiponectin (md: -2.38; 95% CI: -3.59 to -1.17). South Asians also had more body fat (md: 2.69; 95% CI: 0.70 to 4.69), lower lean muscle mass (md: -3.25; 95%CI: -5.35 to -1.14), increased waist to hip ratio (md: 0.03; 95% CI: 0.01-0.05), less superficial subcutaneous abdominal adipose tissue (md: -2.94; 95% CI: -5.56 to-0.32), more deep/visceral to superficial adipose tissue ratio (md 0.34; 95% CI: 0.02 to 0.65), and more liver fat (md: 7.43%; 95% CI: 2.30 to 12.55%). Adipocyte area was increased in South Asians compared to white Caucasians (md: 64.26; 95% CI: 24.3 to 104.1) units(2). Adjustment for adipocyte area attenuated the ethnic differences in insulin (md: 0.22; 95% CI: -0.07 to 0.51), HDL (md: -0.01; 95% CI: -0.16 to 0.13) and adiponectin (md: -1.11; 95% CI: -2.61 to 0.39). Adjustment for differences in adipocyte area and fat distribution attenuated the ethnic difference in liver fat (md: 5.19; 95% CI: 0.31 to 10.06).\n\nCONCLUSION: South Asians have an increased adipocyte area compared to white Caucasians. This difference accounts for the ethnic differences in insulin, HDL cholesterol, adiponectin, and ectopic fat deposition in the liver.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarnopolsky", "given" : "Mark A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rashid", "given" : "Shirya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schulze", "given" : "Karleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mente", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Sandy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Arya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Stanojevic", "given" : "Sanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e22112", "publisher" : "Public Library of Science", "title" : "Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE).", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jcem.84.7.5817", "ISSN" : "0021-972X", "PMID" : "10404798", "abstract" : "It has been proposed that excessive insulin resistance in Asian Indians living in urban areas or migrated to western countries is responsible for the higher incidence of type 2 diabetes and coronary heart disease observed in this population. To evaluate whether Asian Indians are more insulin resistant than Caucasians and to define the role of generalized and truncal adiposity, we performed hydrodensitometry, skinfold measurements, and euglycemic-hyperinsulinemic clamps in 21 healthy Asian Indian men and 23 Caucasian men of similar age and body fat content. The glucose disposal rate (Rd) was significantly lower in the Asian Indians than in the Caucasians (3.7+/-1.3 vs. 5.3+/-2.0 mg/min x kg lean body mass, respectively; P = 0.003). Despite similar total body fat content, Asian Indians had higher truncal adiposity than Caucasians (sum of truncal skinfolds, 117+/-37 and 92.4+/-38 mm, respectively). In both Asian Indians and Caucasians, the insulin sensitivity index (Rd/plasma insulin concentrations) was inversely correlated with both total body fat (r = -0.49; P<0.03 and r = -0.67; P<0.001, respectively) and sum of truncal skinfold thickness (r = -0.55; P<0.001 and r = -0.61; P<0.002, respectively). After adjustment for total body fat and truncal skinfold thickness, Asian Indians still had a significantly lower glucose disposal rate (P = 0.04). These results show that Asian Indian men are more insulin resistant than Caucasian men independently of generalized or truncal adiposity. The excessive insulin resistance in Asian Indians is probably a primary metabolic defect and may account for the excessive morbidity and mortality from diabetes and coronary heart disease in this population.", "author" : [ { "dropping-particle" : "", "family" : "Chandalia", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abate", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garg", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stray-Gundersen", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "1999", "7" ] ] }, "page" : "2329-35", "title" : "Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men.", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0899-9007", "PMID" : "12921898", "author" : [ { "dropping-particle" : "", "family" : "Misra", "given" : "Anoop", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nutrition (Burbank, Los Angeles County, Calif.)", "id" : "ITEM-3", "issue" : "9", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "815-6", "title" : "Impact of ethnicity on body fat patterning in Asian Indians and blacks: relation with insulin resistance.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "39,134,135", "plainTextFormattedCitation" : "39,134,135", "previouslyFormattedCitation" : "39,134,135" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39,134,135. In this context, we hypothesize that the higher risk of dysglycemia observed in South Asians results from a compounded effect of genetic beta-cell impairment in the presence of excess abdominal obesityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0022112", "ISSN" : "1932-6203", "PMID" : "21829446", "abstract" : "OBJECTIVE: We sought to determine if differences in the distribution and characteristics of adipose tissue between South Asians and white Caucasians account for differences in risk factors for cardiovascular disease.\n\nRESEARCH DESIGN AND METHODS: We recruited 108 healthy South Asians (36.8 years) and white Caucasians (34.2 years) within three BMI strata. Body composition, adipocyte size, abdominal fat area, and hepatic adiposity were assessed and related to fasting glucose, insulin, lipids and adiponectin.\n\nRESULTS: After adjustment for age, sex, and BMI, South Asians compared to white Caucasians had higher ln fasting insulin (mean difference (MD): 0.44; 95% CI: 0.20-0.69), lower HDL cholesterol (md: -0.13; 95% CI:-0.26 to -0.01), and lower adiponectin (md: -2.38; 95% CI: -3.59 to -1.17). South Asians also had more body fat (md: 2.69; 95% CI: 0.70 to 4.69), lower lean muscle mass (md: -3.25; 95%CI: -5.35 to -1.14), increased waist to hip ratio (md: 0.03; 95% CI: 0.01-0.05), less superficial subcutaneous abdominal adipose tissue (md: -2.94; 95% CI: -5.56 to-0.32), more deep/visceral to superficial adipose tissue ratio (md 0.34; 95% CI: 0.02 to 0.65), and more liver fat (md: 7.43%; 95% CI: 2.30 to 12.55%). Adipocyte area was increased in South Asians compared to white Caucasians (md: 64.26; 95% CI: 24.3 to 104.1) units(2). Adjustment for adipocyte area attenuated the ethnic differences in insulin (md: 0.22; 95% CI: -0.07 to 0.51), HDL (md: -0.01; 95% CI: -0.16 to 0.13) and adiponectin (md: -1.11; 95% CI: -2.61 to 0.39). Adjustment for differences in adipocyte area and fat distribution attenuated the ethnic difference in liver fat (md: 5.19; 95% CI: 0.31 to 10.06).\n\nCONCLUSION: South Asians have an increased adipocyte area compared to white Caucasians. This difference accounts for the ethnic differences in insulin, HDL cholesterol, adiponectin, and ectopic fat deposition in the liver.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarnopolsky", "given" : "Mark A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rashid", "given" : "Shirya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schulze", "given" : "Karleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mente", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Sandy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Arya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Stanojevic", "given" : "Sanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e22112", "publisher" : "Public Library of Science", "title" : "Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE).", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/ije/dyl245", "ISSN" : "0300-5771", "PMID" : "17510078", "abstract" : "The rates of coronary disease have accelerated dramatically amongst South Asians, driven to an important extent by the atherogenic dyslipidemia and type 2 diabetes that have become so common amongst them. These precursors of vascular disease appear at lower absolute amounts of adipose tissue in South Asians than in whites. In this paper, we set out a new hypothesis--the adipose tissue overflow hypothesis--to account for these findings. The adipose tissue mass within our bodies can be divided into three different compartments: superficial subcutaneous adipose tissue, deep subcutaneous adipose tissue and visceral adipose tissue. The superficial subcutaneous adipose tissue compartment is the primary compartment, is present throughout the body, and constitutes the vast majority of the adipose tissue in the lower limb. With energy excess, the secondary adipose tissue compartments--the deep subcutaneous (mainly upper body) and the visceral adipose tissue compartments--become more prominent. Superficial subcutaneous adipose tissue is relatively inert metabolically, whereas the other two compartments are characterized by higher transmembrane fatty acid flux rates and thus are more closely linked to dyslipidemia and dysglycemia. We hypothesize that the superficial subcutaneous adipose tissue compartment is larger in whites than in South Asians. If so, as obesity develops, South Asians exhaust the storage capacity of their superficial subcutaneous adipose tissue compartment before whites do and that is why they develop the metabolic complications of upper body obesity at lower absolute masses of adipose tissue than white people.", "author" : [ { "dropping-particle" : "", "family" : "Sniderman", "given" : "Allan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhopal", "given" : "Raj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarrafzadegan", "given" : "Nizal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tchernof", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "2", "1" ] ] }, "page" : "220-5", "title" : "Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "39,136", "plainTextFormattedCitation" : "39,136", "previouslyFormattedCitation" : "39,136" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39,136.This hypothesis was tested using data from an international prospective cohort studyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc12-2553", "ISSN" : "1935-5548", "PMID" : "23603917", "abstract" : "OBJECTIVE: To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.\n\nRESEARCH DESIGN AND METHODS: In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.\n\nRESULTS: Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).\n\nCONCLUSIONS: T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Changchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xiaohe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Jackie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keavney", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudet", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "2836-42", "title" : "Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "62" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62. A genotype score of SNPs involved in beta-cell impairment was created and used to investigate: (1) ethnic differences in the effect of beta-cell impairment on glycemic traits, and (2) whether this genetic risk for dysglycemia is compounded by the presence of abdominal obesity. 3.2 Methods3.2.1 ParticipantsDetails of the EpiDREAM cohort and primary results have been reported previouslyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc12-2553", "ISSN" : "1935-5548", "PMID" : "23603917", "abstract" : "OBJECTIVE: To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.\n\nRESEARCH DESIGN AND METHODS: In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.\n\nRESULTS: Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).\n\nCONCLUSIONS: T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Changchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xiaohe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Jackie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keavney", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudet", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "2836-42", "title" : "Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "62" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62. Briefly, 25,063 people from 191 centres in 21 countries were screened and 5,269 were included in the DREAM randomized control trial, which assessed the efficacy of rosiglitazone in reducing progression to diabetes from impaired fasting glucose (IFG) and / or IGTADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(06)69420-8", "ISSN" : "1474-547X", "PMID" : "16997664", "abstract" : "BACKGROUND: Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drug's ability to prevent type 2 diabetes in individuals at high risk of developing the condition.\n\nMETHODS: 5269 adults aged 30 years or more with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive rosiglitazone (8 mg daily; n=2365) or placebo (2634) and followed for a median of 3 years. The primary outcome was a composite of incident diabetes or death. Analyses were done by intention to treat. This trial is registered at , number NCT00095654.\n\nFINDINGS: At the end of study, 59 individuals had dropped out from the rosiglitazone group and 46 from the placebo group. 306 (11.6%) individuals given rosiglitazone and 686 (26.0%) given placebo developed the composite primary outcome (hazard ratio 0.40, 95% CI 0.35-0.46; p<0.0001); 1330 (50.5%) individuals in the rosiglitazone group and 798 (30.3%) in the placebo group became normoglycaemic (1.71, 1.57-1.87; p<0.0001). Cardiovascular event rates were much the same in both groups, although 14 (0.5%) participants in the rosiglitazone group and two (0.1%) in the placebo group developed heart failure (p=0.01).\n\nINTERPRETATION: Rosiglitazone at 8 mg daily for 3 years substantially reduces incident type 2 diabetes and increases the likelihood of regression to normoglycaemia in adults with impaired fasting glucose or impaired glucose tolerance, or both.", "author" : [ { "dropping-particle" : "", "family" : "Gerstein", "given" : "H C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pogue", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheridan", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dinccag", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanefeld", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoogwerf", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaw", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zinman", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holman", "given" : "R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9541", "issued" : { "date-parts" : [ [ "2006", "9", "23" ] ] }, "page" : "1096-105", "title" : "Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial.", "type" : "article-journal", "volume" : "368" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "137", "plainTextFormattedCitation" : "137", "previouslyFormattedCitation" : "137" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }137. Individuals ineligible for the DREAM trial or those who declined to participate were enrolled in the EpiDREAM cohort. Inclusion in the cohort was determined using family history, ethnicity, and abdominal obesity. Participants were followed for a median of 3.3 years. DNA was obtained at baseline. Buffy coat DNA extractions and genotyping was successful for 19,197 subjects; 711 of which were excluded because of genotyping failure (defined as <97% of genotypes called), leaving 18,486 eligible for genetic study. For the present analysis, only baseline biochemical and anthropometric measures of 2,764 participants of South Asian descent and 9,408 white Caucasians of European origin were used.3.2.2 SNP selection and genotype scoreEvidence from published literature was used to identify genes robustly implicated in beta-cell impairment. Specifically, GWA-studies, functional, and animal studies were used to identify genes associated with beta-cell function. Details of the evidence considered are presented in Figure 3.1. SNPs on genes that had conflicting evidence for beta cell impairment, such as genes shown to be associated with both beta-cell impairment and insulin sensitivity were excluded. Based on these criteria, 29 SNPs on 25 genes were identified. Data for 11 of these SNPs were available in the EpiDREAM cohort in both South Asians and Caucasians, and were used to create a beta-cell impairment genotype score. For each SNP, the glucose-elevating allele was used as the risk allele. An unweighted genotype score was created in accordance with recommendations by Janssens et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/GIM.0b013e31812eece0", "ISSN" : "1098-3600", "abstract" : "Purpose: Single genetic variants in multifactorial disorders typically have small effects, so major increases in disease risk are expected only from the simultaneous exposure to multiple risk genotypes. We investigated the impact of genotype frequencies on the clinical discriminative accuracy for the simultaneous testing of 40 independent susceptibility genetic variants.", "author" : [ { "dropping-particle" : "", "family" : "Janssens", "given" : "A Cecile J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moonesinghe", "given" : "Ramal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Quahne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steyerberg", "given" : "Ewout W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khoury", "given" : "Muin J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics in Medicine", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8" ] ] }, "page" : "528-535", "publisher" : "The American College of Medical Genetics", "title" : "The impact of genotype frequencies on the clinical validity of genomic profiling for predicting common chronic diseases", "title-short" : "Genet Med", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "138", "plainTextFormattedCitation" : "138", "previouslyFormattedCitation" : "138" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }138 and since weights from large GWA-studies are not readily available for South Asians. Genotypes were coded as 0, 1, and 2, designating copies of the risk allele and the score was calculated for each individual by allele counting. The score could range from 0 to 22. A higher genotype score designated greater beta-cell impairment. Figure 3. SEQ Figure_3.1 \* ARABIC 1 Criteria for selection and inclusion of SNPs implicated in beta-cell function3.2.3 Genotyping and sample quality controlGenotyping was performed at McGill University and the Genome Quebec Innovation Centre using the 50 K Illumina CVD bead chip microarray ITMAT Broad Care (IBC) arrayADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0003583", "ISSN" : "1932-6203", "PMID" : "18974833", "abstract" : "A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a \"cosmopolitan\" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.", "author" : [ { "dropping-particle" : "", "family" : "Keating", "given" : "Brendan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tischfield", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murray", "given" : "Sarah S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhangale", "given" : "Tushar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glessner", "given" : "Joseph T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galver", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrett", "given" : "Jeffrey C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "Struan F A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farlow", "given" : "Deborah N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandrupatla", "given" : "Hareesh R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ajmal", "given" : "Saad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papanicolaou", "given" : "George J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guo", "given" : "Yiran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Mingyao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Derohannessian", "given" : "Stephanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edmondson", "given" : "Andrew C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "Kent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gai", "given" : "Xiaowu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Susanna S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fornage", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaikh", "given" : "Tamim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Alistair S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frackelton", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiang", "given" : "Charleston W K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Cecelia E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fabsitz", "given" : "Richard R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouwehand", "given" : "Willem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munroe", "given" : "Patricia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drake", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitehead", "given" : "A Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappola", "given" : "Thomas P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samani", "given" : "Nilesh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lusis", "given" : "A Jake", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schadt", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koenig", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabriel", "given" : "Stacey B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hakonarson", "given" : "Hakon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reilly", "given" : "Muredach", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nickerson", "given" : "Deborah A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fitzgerald", "given" : "Garret A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "e3583", "title" : "Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "139", "plainTextFormattedCitation" : "139", "previouslyFormattedCitation" : "139" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }139. This array includes 49,234 genetic markers enriched in SNPs of candidate genes and pathways for cardiovascular, inflammatory and metabolic phenotypes. Design of this array was led by Institute of Translational Medicine and Therapeutics (ITMAT), the Broad Institute, and the National Heart Lung and Blood Institute (NHLBI). Further details of the design and conceptualization are presented by Keating et alADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0003583", "ISSN" : "1932-6203", "PMID" : "18974833", "abstract" : "A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a \"cosmopolitan\" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.", "author" : [ { "dropping-particle" : "", "family" : "Keating", "given" : "Brendan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tischfield", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murray", "given" : "Sarah S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhangale", "given" : "Tushar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glessner", "given" : "Joseph T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galver", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrett", "given" : "Jeffrey C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "Struan F A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farlow", "given" : "Deborah N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandrupatla", "given" : "Hareesh R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ajmal", "given" : "Saad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papanicolaou", "given" : "George J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guo", "given" : "Yiran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Mingyao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Derohannessian", "given" : "Stephanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edmondson", "given" : "Andrew C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "Kent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gai", "given" : "Xiaowu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Susanna S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fornage", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaikh", "given" : "Tamim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Alistair S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frackelton", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiang", "given" : "Charleston W K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Cecelia E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fabsitz", "given" : "Richard R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouwehand", "given" : "Willem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munroe", "given" : "Patricia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drake", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitehead", "given" : "A Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappola", "given" : "Thomas P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samani", "given" : "Nilesh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lusis", "given" : "A Jake", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schadt", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koenig", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabriel", "given" : "Stacey B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hakonarson", "given" : "Hakon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reilly", "given" : "Muredach", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nickerson", "given" : "Deborah A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fitzgerald", "given" : "Garret A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "e3583", "title" : "Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "139", "plainTextFormattedCitation" : "139", "previouslyFormattedCitation" : "139" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }139. Standard assessments were conducted to ensure quality of genotyping. All SNPs included in our analysis (described above) were in agreement with Hardy Weinberg Equilibrium (P<1.00x10-3), had a minor allele frequency ≥ 5%, and displayed call rates greater than 95% (Supplementary Table 3.1). Individuals with more than 5% missing genotypes were excluded. Missing values for the remaining individuals in the genotype score were imputed using the arithmetic average of the coded genotypes. After quality control, data from 2,651 South Asians and 9,408 Caucasians were available for analysis.3.2.4 Population structure and inbreedingPresence of population stratification and inbreeding was assessed using array-wide genotyping data for South Asians and white Caucasians from the 50K IBC array. Principle components analysis (PCA) with 20 axes of variation was conducted to assess population stratification within South Asian and white Caucasian groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng1847", "ISSN" : "1061-4036", "PMID" : "16862161", "abstract" : "Population stratification--allele frequency differences between cases and controls due to systematic ancestry differences-can cause spurious associations in disease studies. We describe a method that enables explicit detection and correction of population stratification on a genome-wide scale. Our method uses principal components analysis to explicitly model ancestry differences between cases and controls. The resulting correction is specific to a candidate marker's variation in frequency across ancestral populations, minimizing spurious associations while maximizing power to detect true associations. Our simple, efficient approach can easily be applied to disease studies with hundreds of thousands of markers.", "author" : [ { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plenge", "given" : "Robert M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinblatt", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shadick", "given" : "Nancy A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2006", "8" ] ] }, "page" : "904-9", "title" : "Principal components analysis corrects for stratification in genome-wide association studies.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "140", "plainTextFormattedCitation" : "140", "previouslyFormattedCitation" : "140" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }140. Secondly, coefficients of inbreeding were calculated based on observed and expected number of homozygous genotypes. The coefficient of inbreeding (F) measures the probability that two genes at any locus are identical by descent from the common ancestor(s)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Wright", "given" : "Sewall", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Naturalist", "id" : "ITEM-1", "issue" : "645", "issued" : { "date-parts" : [ [ "1922" ] ] }, "page" : "330-338", "title" : "Coefficients of Inbreeding and Relationship", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "141", "plainTextFormattedCitation" : "141", "previouslyFormattedCitation" : "141" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }141 – the degree to which two alleles are more likely to be homozygous in an individual because the parents are related. As F is a relative measure, it estimates the increase in homozygosity from the base population. In the present study, F was estimated using a sub-set of SNPs that were pruned to be in approximate linkage equilibrium (18,424 SNPs for South Asians and 21,849 SNPs for white Caucasians). Analyses were conducted using PLINK (version 1.9)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/519795", "ISSN" : "0002-9297", "PMID" : "17701901", "abstract" : "Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.", "author" : [ { "dropping-particle" : "", "family" : "Purcell", "given" : "Shaun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neale", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todd-Brown", "given" : "Kathe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Lori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Manuel A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bender", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maller", "given" : "Julian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sklar", "given" : "Pamela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "559-75", "title" : "PLINK: a tool set for whole-genome association and population-based linkage analyses.", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "142", "plainTextFormattedCitation" : "142", "previouslyFormattedCitation" : "142" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }142 and Genome-wide Complex Trait Analysis () version 1.02ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajhg.2010.11.011", "ISSN" : "1537-6605", "PMID" : "21167468", "abstract" : "For most human complex diseases and traits, SNPs identified by genome-wide association studies (GWAS) explain only a small fraction of the heritability. Here we report a user-friendly software tool called genome-wide complex trait analysis (GCTA), which was developed based on a method we recently developed to address the \"missing heritability\" problem. GCTA estimates the variance explained by all the SNPs on a chromosome or on the whole genome for a complex trait rather than testing the association of any particular SNP to the trait. We introduce GCTA's five main functions: data management, estimation of the genetic relationships from SNPs, mixed linear model analysis of variance explained by the SNPs, estimation of the linkage disequilibrium structure, and GWAS simulation. We focus on the function of estimating the variance explained by all the SNPs on the X chromosome and testing the hypotheses of dosage compensation. The GCTA software is a versatile tool to estimate and partition complex trait variation with large GWAS data sets.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Jian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "S Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goddard", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visscher", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "7" ] ] }, "page" : "76-82", "title" : "GCTA: a tool for genome-wide complex trait analysis.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "143", "plainTextFormattedCitation" : "143", "previouslyFormattedCitation" : "143" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }143.3.2.5 MatchingThe baseline characteristics of the eligible South Asians (n=2,651) and white Caucasians (n=9,408) from the EpiDREAM cohort varied substantially in age and male to female ratio. Specifically, the South Asian cohort was 10 years younger (Mean age South Asians: 44.97 (SD=9.38); Mean age white Caucasians: 54.98 (SD=10.82)) and had a lower proportion of females (48.4% compared to 60.8%, respectively). To avoid bias from differences in these baseline characteristics, the ethnic groups were matched 1:1 by age (±5 years) and sexADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/00273171.2011.568786", "ISSN" : "0027-3171", "PMID" : "21818162", "abstract" : "The propensity score is the probability of treatment assignment conditional on observed baseline characteristics. The propensity score allows one to design and analyze an observational (nonrandomized) study so that it mimics some of the particular characteristics of a randomized controlled trial. In particular, the propensity score is a balancing score: conditional on the propensity score, the distribution of observed baseline covariates will be similar between treated and untreated subjects. I describe 4 different propensity score methods: matching on the propensity score, stratification on the propensity score, inverse probability of treatment weighting using the propensity score, and covariate adjustment using the propensity score. I describe balance diagnostics for examining whether the propensity score model has been adequately specified. Furthermore, I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data. I describe different causal average treatment effects and their relationship with propensity score analyses.", "author" : [ { "dropping-particle" : "", "family" : "Austin", "given" : "Peter C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Multivariate behavioral research", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "399-424", "title" : "An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "144", "plainTextFormattedCitation" : "144", "previouslyFormattedCitation" : "144" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }144. As a result, 2,651 South Asians were matched to 2,651 white Caucasians and included in this analysis.3.2.6 OutcomesMain outcomes: The association with beta-cell genotype score was tested with two glycemic traits: i) the area under the curve (AUC), which uses the FPG and 2 hour post 75 gram OGTT load glucose values (2hrGlu), and is calculated as ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/diacare.13.2.172", "ISSN" : "0149-5992", "PMID" : "2351014", "abstract" : "To specify the influence of methods used in estimating area under the curve (AUC) and the meaning of total and incremental AUC, 75 glycemic responses to a mixed meal were studied in 75 diabetic patients, 39 with insulin-dependent diabetes mellitus and 36 with non-insulin-dependent diabetes mellitus. AUC was integrated with five computerized methods: polynomial interpolation of third and fourth degree, trapezoidal rule, Simpson's integration, and cubic interpolatory splines. Although these methods gave significantly different results (P less than 0.001), a strong correlation was found between estimations of AUC with different methods (r greater than 0.99, P less than 0.001). In addition, variation between methods was less than or equal to 2%, whereas the coefficient of variation between subjects was 38%. Total AUC was strongly correlated with basal blood glucose value (r = 0.90, P less than 0.001), whereas incremental and positive AUC were not (r = 0.12 and 0.07, respectively, NS). Incremental and positive AUC were strongly correlated with glycemic rise (r = 0.89 and 0.93, respectively, P less than 0.001), whereas total AUC was only slightly so (r = 0.31, P less than 0.01). Incremental and positive AUC gave slightly but significantly different information on glucose response. These results suggest that variations related to the method used in estimating AUC are not clinically relevant and that a simple method such as trapezoidal rule can be used. Total AUC is a descriptive factor related to basal blood glucose value, whereas incremental and positive AUC more accurately describe glycemic response to foods.", "author" : [ { "dropping-particle" : "", "family" : "Floch", "given" : "J. P.", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Escuyer", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baudin", "given" : "E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baudon", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perlemuter", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes Care", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "1990", "2", "1" ] ] }, "page" : "172-175", "title" : "Blood glucose area under the curve. Methodological aspects", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "145", "plainTextFormattedCitation" : "145", "previouslyFormattedCitation" : "145" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }145: AUC = (2-0)*{[FPG + 2hGlu]/2}, and ii) FPG level, measured after an overnight fast.Beta-cell impairment: While the primary purpose of this paper was to assess the effect of the beta-cell genotype score on glycemic traits, an oral disposition index (ODI) was also used to quantify the effect of the genotype score on beta-cell function. This analysis was performed in a subset of 701 individuals of both South Asian and white Caucasian ethnicities in whom the ODI was availableADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc09-1579", "ISSN" : "1935-5548", "PMID" : "20009095", "abstract" : "OBJECTIVE The objective of this study was to determine the degree to which ramipril and/or rosiglitazone changed beta-cell function over time among individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) who participated in the Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication (DREAM) Trial, which evaluated whether ramipril and/or rosiglitazone could prevent or delay type 2 diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS The present analysis included subjects (n = 982) from DREAM trial centers in Canada who had oral glucose tolerance tests at baseline, after 2 years, and at the end of the study. beta-Cell function was assessed using the fasting proinsulin-to-C-peptide ratio (PI/C) and the insulinogenic index (defined as 30-0 min insulin/30-0 min glucose) divided by homeostasis model assessment of insulin resistance (insulinogenic index [IGI]/insulin resistance [IR]). RESULTS Subjects receiving rosiglitazone had a significant increase in IGI/IR between baseline and end of study compared with the placebo group (25.59 vs. 1.94, P < 0.0001) and a significant decrease in PI/C (-0.010 vs. -0.006, P < 0.0001). In contrast, there were no significant changes in IGI/IR or PI/C in subjects receiving ramipril compared with placebo (11.71 vs. 18.15, P = 0.89, and -0.007 vs. -0.008, P = 0.64, respectively). The impact of rosiglitazone on IGI/IR and PI/C was similar within subgroups of isolated IGT and IFG + IGT (all P < 0.001). Effects were more modest in those with isolated IFG (IGI/IR: 8.95 vs. 2.13, P = 0.03; PI/C: -0.003 vs. -0.001, P = 0.07). CONCLUSIONS Treatment with rosiglitazone, but not ramipril, resulted in significant improvements in measures of beta-cell function over time in pre-diabetic subjects. Although the long-term sustainability of these improvements cannot be determined from the present study, these findings demonstrate that the diabetes preventive effect of rosiglitazone was in part a consequence of improved beta-cell function.", "author" : [ { "dropping-particle" : "", "family" : "Hanley", "given" : "Anthony J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zinman", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheridan", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "608-13", "title" : "Effect of Rosiglitazone and Ramipril on {beta}-cell function in people with impaired glucose tolerance or impaired fasting glucose: the DREAM trial.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "146", "plainTextFormattedCitation" : "146", "previouslyFormattedCitation" : "146" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }146. This subset of individuals was selected for a DREAM sub-study assessing the effect of rosiglitazone and ramipril on beta-cell function. The participants in this subset were from Canadian study centers and had OGTTs at baseline, after 2 years, and at the end of the study, with blood samples drawn fasting as well as 30 and 120 min after the glucose challengeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc09-1579", "ISSN" : "1935-5548", "PMID" : "20009095", "abstract" : "OBJECTIVE The objective of this study was to determine the degree to which ramipril and/or rosiglitazone changed beta-cell function over time among individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) who participated in the Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication (DREAM) Trial, which evaluated whether ramipril and/or rosiglitazone could prevent or delay type 2 diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS The present analysis included subjects (n = 982) from DREAM trial centers in Canada who had oral glucose tolerance tests at baseline, after 2 years, and at the end of the study. beta-Cell function was assessed using the fasting proinsulin-to-C-peptide ratio (PI/C) and the insulinogenic index (defined as 30-0 min insulin/30-0 min glucose) divided by homeostasis model assessment of insulin resistance (insulinogenic index [IGI]/insulin resistance [IR]). RESULTS Subjects receiving rosiglitazone had a significant increase in IGI/IR between baseline and end of study compared with the placebo group (25.59 vs. 1.94, P < 0.0001) and a significant decrease in PI/C (-0.010 vs. -0.006, P < 0.0001). In contrast, there were no significant changes in IGI/IR or PI/C in subjects receiving ramipril compared with placebo (11.71 vs. 18.15, P = 0.89, and -0.007 vs. -0.008, P = 0.64, respectively). The impact of rosiglitazone on IGI/IR and PI/C was similar within subgroups of isolated IGT and IFG + IGT (all P < 0.001). Effects were more modest in those with isolated IFG (IGI/IR: 8.95 vs. 2.13, P = 0.03; PI/C: -0.003 vs. -0.001, P = 0.07). CONCLUSIONS Treatment with rosiglitazone, but not ramipril, resulted in significant improvements in measures of beta-cell function over time in pre-diabetic subjects. Although the long-term sustainability of these improvements cannot be determined from the present study, these findings demonstrate that the diabetes preventive effect of rosiglitazone was in part a consequence of improved beta-cell function.", "author" : [ { "dropping-particle" : "", "family" : "Hanley", "given" : "Anthony J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zinman", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheridan", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "608-13", "title" : "Effect of Rosiglitazone and Ramipril on {beta}-cell function in people with impaired glucose tolerance or impaired fasting glucose: the DREAM trial.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "146", "plainTextFormattedCitation" : "146", "previouslyFormattedCitation" : "146" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }146. The ODI uses fasting and post glucose load glucose and insulin values at baseline and 30 minutes, and represents the relationship between insulin sensitivity and action. The ODI has been shown to correlate with pancreatic beta-cell impairment; a low ODI indicates poor beta-cell functionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc08-1478", "ISSN" : "1935-5548", "PMID" : "18957530", "abstract" : "OBJECTIVE: We sought to determine whether an oral disposition index (DI(O)) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DI(O) by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and beta-cell function.\n\nRESEARCH DESIGN AND METHODS: A total of 613 Japanese-American subjects (322 men and 291 women) underwent a 75-g oral glucose tolerance test (OGTT) at baseline, 5 years, and 10 years. Insulin sensitivity was estimated as 1/fasting insulin or homeostasis model assessment of insulin sensitivity (HOMA-S). Insulin response was estimated as the change in insulin divided by change in glucose from 0 to 30 min (DeltaI(0-30)/DeltaG(0-30)).\n\nRESULTS: DeltaI(0-30)/DeltaG(0-30) demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S with a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the log(e)-transformed estimates included -1 for DeltaI(0-30)/DeltaG(0-30) versus 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin sensitivity measure, the confidence limits for the slope included -1 only for subjects with normal glucose tolerance (NGT) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of DeltaI(0-30)/DeltaG(0-30) and 1/fasting insulin was calculated (DI(O)) and decreased from NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DI(O) predicted cumulative diabetes at 10 years (P < 0.001) independent of age, sex, BMI, family history of diabetes, and baseline fasting and 2-h glucose concentrations.\n\nCONCLUSIONS: The DI(O) provides a measure of beta-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.", "author" : [ { "dropping-particle" : "", "family" : "Utzschneider", "given" : "Kristina M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prigeon", "given" : "Ronald L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Faulenbach", "given" : "Mirjam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tong", "given" : "Jenny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carr", "given" : "Darcy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boyko", "given" : "Edward J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leonetti", "given" : "Donna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNeely", "given" : "Marguerite J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fujimoto", "given" : "Wilfred Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kahn", "given" : "Steven E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "2" ] ] }, "page" : "335-41", "title" : "Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels.", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "147", "plainTextFormattedCitation" : "147", "previouslyFormattedCitation" : "147" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }147. The ODI is calculated as {ΔI0-30/ΔG0-30} x {1/fasting insulin}, where ΔI0-30/ΔG0-30 is the ratio of the change in insulin to the change in glucose from 0 to 30 min.3.2.7 Abdominal obesityThe primary measure of abdominal obesity utilized in this analysis was the waist circumference adjusted for hip circumference (WaistadjHip) since this has been shown to most robustly predict type 2 diabetes and cardiovascular disease in the EpiDREAM cohort and other studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurheartj/ehm026", "ISSN" : "0195-668X", "PMID" : "17403720", "abstract" : "AIMS: The objectives of this study were to determine the association of waist circumference (WC) and waist-to-hip ratio (WHR) with the risk of incident cardiovascular disease (CVD) events and to determine whether the strength of association of WC and WHR with CVD risk is different.\n\nMETHODS AND RESULTS: This meta-regression analysis used a search strategy of keywords and MeSH terms to identify prospective cohort studies and randomized clinical trials of CVD risk and abdominal obesity from the Medline, Embase, and Cochrane databases. Fifteen articles (n = 258 114 participants, 4355 CVD events) reporting CVD risk by categorical and continuous measures of WC and WHR were included. For a 1 cm increase in WC, the relative risk (RR) of a CVD event increased by 2% (95% CI: 1-3%) overall after adjusting for age, cohort year, or treatment. For a 0.01 U increase in WHR, the RR increased by 5% (95% CI: 4-7%). These results were consistent in men and women. Overall risk estimates comparing the extreme quantiles of each measure suggested that WHR was more strongly associated with CVD than that for WC (WHR: RR = 1.95, 95% CI: 1.55-2.44; WC: RR = 1.63, 95% CI: 1.31-2.04), although this difference was not significant. The strength of association for each measure was similar in men and women.\n\nCONCLUSION: WHR and WC are significantly associated with the risk of incident CVD events. These simple measures of abdominal obesity should be incorporated into CVD risk assessments.", "author" : [ { "dropping-particle" : "", "family" : "Koning", "given" : "Lawrence", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Merchant", "given" : "Anwar T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pogue", "given" : "Janice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European heart journal", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "page" : "850-6", "title" : "Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies.", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00125-010-1710-3", "ISSN" : "0012-186X", "PMID" : "20372875", "abstract" : "AIMS/HYPOTHESES: We determined: (1) which of BMI, waist circumference, hip circumference and WHR has the strongest association and explanatory power for newly diagnosed type 2 diabetes and glucose status; and (2) the impact of considering two measures simultaneously. We also explored variation in anthropometric associations by sex and ethnicity.\n\nMETHODS: We performed cross-sectional analysis of 22,293 men and women who were from five ethnic groups and 21 countries, and at risk of developing type 2 diabetes. Standardised anthropometric associations with type 2 diabetes and AUC of glucose status from OGTT (AUC(OGTT)) were determined using multiple regression. Explanatory power was assessed using the c-statistic and adjusted r (2).\n\nRESULTS: An increase in BMI, waist circumference or WHR had similar positive associations with type 2 diabetes, AUC(OGTT) and explanatory power after adjustment for age, sex, smoking and ethnicity (p < 0.01). However, using BMI and WHR together resulted in greater explanatory power than with other models (p < 0.01). Associations were strongest when waist circumference and hip circumference were used together, a combination that had greater explanatory power than other models except for BMI and WHR together (p < 0.01). Results were directionally similar according to sex and ethnicity; however, significant variations in associations were observed among these subgroups.\n\nCONCLUSIONS/INTERPRETATION: The combination of BMI and WHR, or of waist circumference and hip circumference has the best explanatory power for type 2 diabetes and glucose status compared with a single anthropometric measure. Measurement of waist circumference and hip circumference is required to optimally identify people at risk of type 2 diabetes and people with elevated glucose levels.", "author" : [ { "dropping-particle" : "", "family" : "Koning", "given" : "L.", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "H. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dagenais", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "4", "7" ] ] }, "page" : "1322-1330", "title" : "Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/HJR.0b013e32833c1aa3", "ISSN" : "1741-8275", "PMID" : "20628304", "abstract" : "AIMS: The aim of this study was to compare the strength of associations and discrimination capability of body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) with cardiovascular disease risk in individuals with type-2 diabetes.\n\nMETHODS AND RESULTS: Eleven thousand, one hundred and forty men and women were followed for a mean of 4.8 years. The Cox proportional hazard models were used to compute the hazard ratios and 95% confidence intervals (95% CI) for one standard deviation (SD) increase in baseline BMI (SD: 5 kg/m2), WC (SD: 13 cm) and WHR (SD: 0.08) with cardiovascular disease risk. After adjustment, hazard ratio (95% CI) for WC were 1.10 (1.03\u20131.18) for cardiovascular events, 1.13 (1.03\u20131.24) for coronary events, and 1.08 (0.98\u20131.19) for cardiovascular deaths. Estimates for WHR were 1.12 (1.05\u20131.19), 1.17 (1.08\u20131.28) and 1.19 (1.09\u20131.31). BMI was not related to any of these outcomes. Although the receiver operating characteristic curve could not differentiate between anthropometric variables (P values 0.24), the relative integrated discrimination improvement statistic showed an enhancement in the discrimination capabilities of models using WHR for cardiovascular outcomes, except for cerebrovascular events.\n\nCONCLUSION: Strengths of associations and discrimination statistics suggested that WHR was the best predictor of cardiovascular events and mortality in patients with type-2 diabetes and BMI the worst.", "author" : [ { "dropping-particle" : "", "family" : "Czernichow", "given" : "S\u00e9bastien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kengne", "given" : "Andre-Pascal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huxley", "given" : "Rachel R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Batty", "given" : "George David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Bastiaan", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pillai", "given" : "Avinesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zoungas", "given" : "Sophia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woodward", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neal", "given" : "Bruce", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chalmers", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2011", "4" ] ] }, "page" : "312-9", "title" : "Comparison of waist-to-hip ratio and other obesity indices as predictors of cardiovascular disease risk in people with type-2 diabetes: a prospective cohort study from ADVANCE.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "148\u2013150", "plainTextFormattedCitation" : "148\u2013150", "previouslyFormattedCitation" : "148\u2013150" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }148–150. WaistadjHip was ascertained using residuals from a regression of waist circumference on hip circumference.3.2.8 Statistical analysesAnalyses were performed using PLINK () (version 1.9)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/519795", "ISSN" : "0002-9297", "PMID" : "17701901", "abstract" : "Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.", "author" : [ { "dropping-particle" : "", "family" : "Purcell", "given" : "Shaun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neale", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todd-Brown", "given" : "Kathe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Lori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Manuel A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bender", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maller", "given" : "Julian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sklar", "given" : "Pamela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "559-75", "title" : "PLINK: a tool set for whole-genome association and population-based linkage analyses.", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "142", "plainTextFormattedCitation" : "142", "previouslyFormattedCitation" : "142" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }142 and R (version 3.0.2). The total genotype score was compared between the ethnic groups using an independent sample’s t-test. The association between the genotype score and glucose traits was evaluated using linear regression, adjusted for age, sex, ethnicity, and BMI. An ethnicity x genotype score interaction term was included to assess the presence of ethnic heterogeneity in the effect of the genotype score on glucose traits. To investigate if beta-cell impairment varies by levels of abdominal obesity in the ethnic groups, a three-way interaction term between the beta-cell genotype score, measure of abdominal obesity, and ethnicity was included in the regression analyses. The analysis was then stratified by ethnicity to quantify the differences in the interaction of genotype score with abdominal obesity comparing South Asians and white Caucasians. Lastly, a linear regression analysis was performed between the genotype score and ODI, adjusted for age, sex, and ethnicity, to estimate the effect of the genotype score on pancreatic beta-cell dysfunction. A P value of ≤ 0.05 was considered statistically significant.3.3 ResultsAs shown in Table 3.1, after matching South Asians and White Caucasians for age and sex, difference in some demographic and physical characteristics were identified. Briefly, South Asians had comparable abdominal obesity (WHR) at a lower BMI as white Caucasians. The proportion of individuals with type 2 diabetes was greater in South Asians, and there was less IFG. No difference in the proportion of individuals with IGT between the two groups. Histograms of AUC glucose and fasting glucose are provided in Supplementary Figure 3.1.3.3.1 Association of beta-cell genotype score with glucose traitsThe average genotype score was lower in South Asians (mean=11.65, SD=2.02) compared to white Caucasians (mean=12.22 (SD=2.13) (P for mean difference < 0.001). However, the median genotype score was the same (median = 12.00), indicating that a comparable burden of these 11 beta-cell impairment SNPs likely exists among the ethnic groups.Although the absolute values of the beta-cell genotype score did not substantially differ between South Asians and white Caucasians, its effect on AUC glucose and fasting glucose significantly varied. The per-allele increase in AUC glucose was 0.23 mmol/L in South Asians, compared to only 0.08 mmol/L in white Caucasians (P for ethnic heterogeneity = 1.79x10-2). Similarly, the per-allele increase in fasting glucose was 0.07 mmol/L in South Asians compared to 0.02 mmol/L in white Caucasians (P ethnic heterogeneity = 6.29x10-3) (Table 3.2). Furthermore, the genotype score was associated with score predicted a decrease in beta-cell function, measured using an ODI; ODI decreased by 0.01 pM-1 for each risk allele (P=4.80x10-2).Table 3. SEQ Table_3. \* ARABIC 1 Summary characteristics of included participants from the EpiDREAM cohort South Asians (n=2,651)Mean (SD) / %White Caucasians (n=2,651)Mean (SD) / %P ethnic heterogeneityAge (years)44.97 (9.38)45.49 (8.96)3.72x10-2% women51.5747.191.44x10-3Waist adjusted for hip-0.320.441.61x10-2WHR0.89 (0.09)0.89 (0.09)3.15x10-1BMI (in kg/m2)26.46 (4.35)30.71 (6.05)2.82x10-174Fasting glucose (mmol/l)5.39 (1.87)5.56 (1.17)7.10x10-5AUC glucose (mmol/l)13.31 (5.82)12.68 (3.80)3.14x10-6% IGT20.6022.181.60x10-1% IFG6.3713.474.50x10-18% Baseline type 2 diabetes16.0311.663.91x10-6Table 3. SEQ Table_3. \* ARABIC 2 Effect of the genotype score on glucose traits stratified by ethnicityTraitSouth AsiansWhite CaucasiansP ethnic heterogeneityAUC glucoseβ-coefficient (SE)*0.23 (0.05)0.08 (0.03)1.79x10-2P2.38x10-52.32x10-2Fasting glucoseβ-coefficient (SE)*0.07 (0.02)0.02 (0.01)6.29x10-3P6.17x10-58.08x10-2* β-coefficients are adjusted for age, sex, and BMI3.3.2 Ethnic heterogeneity in interaction of beta-cell genotype score with abdominal obesityTo assess the hypothesis that ethnic difference in the effect of the genotype score on glucose traits may be influenced by abdominal adiposity, a three-way interaction of abdominal obesity measured by WaistadjHip, beta-cell genotype score, and ethnicity was tested. The three-way interaction was significant for both AUC (P=1.51x10-2) and fasting glucose (P=2.55x10-2). When stratified by ethnicity, the interaction between genotype score and WaistadjHip was significant in South Asians, but not in white Caucasians (Figure 3.2), indicating that the genetic predisposition to beta-cell impairment is magnified by increasing abdominal obesity in South Asians. The same trend was observed for the interaction between waist circumference and the genotype score (data not shown).Figure 3. SEQ Figure_3.1 \* ARABIC 2 Interaction between beta-cell genotype score and abdominal obesity stratified by ethnic group3.3.3 Population structure and inbreedingAnalysis of population stratification using PCA revealed no evidence of clustering within white Caucasians or South Asians (Supplementary Figure 3.2). An analysis of inbreeding was also performed in both ethnic groups. Coefficients of inbreeding (F) were calculated to estimate the degree of pedigree collapse within an individual’s genealogy. On average, F was 1.81% for South Asians and 0.57% for white Caucasians (Supplementary Figure 3.3), suggesting a greater degree of inbreeding among South Asians. 3.4 DiscussionIn an at risk population for dysglycemia, the genetic load of beta-cell impairment between South Asian and white Caucasians was similar, but the genotype score was more strongly associated with glucose traits among South Asians than white Caucasians. Additionally the per-allele increase in dysglycemia was magnified in South Asians with greater abdominal obesity, which was not observed in white Caucasians.3.4.1 Association of beta-cell genotype score with glucose traitsA genotype score of 11 beta-cell impairment SNPs was similar between the two ethnicities (an absolute difference of 0.57 on a scale of 0 to 22), suggesting that a comparable genetic load for impaired pancreatic function exists. However, the association of the per-allele effect size on glucose traits was greater in South Asians. For example, the per-allele increase for AUC glucose in South Asians was 0.23 mmol/L compared to 0.08 mmol/L in white Caucasians. Such a heterogeneous effect in the genetic association of glucose traits between South Asians and white Caucasians has not been reported previouslyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-014-3354-1", "ISSN" : "1432-0428", "PMID" : "25145545", "abstract" : "AIMS/HYPOTHESIS: South Asians are up to four times more likely to develop type 2 diabetes than white Europeans. It is postulated that the higher prevalence results from greater genetic risk. To evaluate this hypothesis, we: (1) systematically reviewed the literature for single nucleotide polymorphisms (SNPs) predisposing to type 2 diabetes in South Asians; (2) compared risk estimates, risk alleles and risk allele frequencies of predisposing SNPs between South Asians and white Europeans; and (3) tested the association of novel SNPs discovered from South Asians in white Europeans.\n\nMETHODS: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane registry were searched for studies of genetic variants associated with type 2 diabetes in South Asians. Meta-analysis estimates for common and novel bi-allelic SNPs in South Asians were compared with white Europeans from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. The population burden from predisposing SNPs was assessed using a genotype score.\n\nRESULTS: Twenty-four SNPs from 21 loci were associated with type 2 diabetes in South Asians after meta-analysis. The majority of SNPs increase odds of the disorder by 15-35% per risk allele. No substantial differences appear to exist in risk estimates between South Asians and white Europeans from SNPs common to both groups, and the population burden also does not differ. Eight of the 24 are novel SNPs discovered from South Asian genome-wide association studies, some of which show nominal associations with type 2 diabetes in white Europeans.\n\nCONCLUSIONS/INTERPRETATION: Based on current literature there is no strong evidence to indicate that South Asians possess a greater genetic risk of type 2 diabetes than white Europeans.", "author" : [ { "dropping-particle" : "", "family" : "Sohani", "given" : "Zahra N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Wei Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014", "8", "22" ] ] }, "title" : "Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.2897", "ISSN" : "1546-1718", "PMID" : "24509480", "abstract" : "To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.", "author" : [ { "dropping-particle" : "", "family" : "DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "South Asian Type 2 Diabetes (SAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mexican American Type 2 Diabetes (MAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Go", "given" : "Min Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Below", "given" : "Jennifer E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horikoshi", "given" : "Momoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Maggie C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adair", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldassarre", "given" : "Damiano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bao", "given" : "Yuqian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "Graeme I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Qiuyin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carey", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "Juliana C N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Li-Ching", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Tien-Jyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yi-Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chien-Hsiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuan-Tsong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Nam H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Young Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chuang", "given" : "Lee-Ming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crenshaw", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donnelly", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorkhan", "given" : "Mozhgan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Josee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edkins", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erbel", "given" : "Raimund", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Escobedo", "given" : "Jorge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esko", "given" : "Tonu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eury", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontanillas", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsen", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraser", "given" : "Ross M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gao", "given" : "Yutang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gertow", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Bok-Ghee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmen", "given" : "Oddgeir L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hovingh", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hreidarsson", "given" : "Astradur B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunt", "given" : "Sarah E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikegami", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jia", "given" : "Weiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jockel", "given" : "Karl-Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Hyun Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen Hong L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "Ann M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Hassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hyung-Lae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Sangsoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Young Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinnunen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korpi-Hyovalti", "given" : "Eeva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kravic", "given" : "Jasmina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krithika", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Ashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumate", "given" : "Jesus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwak", "given" : "Soo Heon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langford", "given" : "Cordelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leander", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jen-Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Nanette R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindholm", "given" : "Eero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jian Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Long", "given" : "Jirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ma", "given" : "Ronald C W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mannisto", "given" : "Satu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metspalu", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mirza", "given" : "Ghazala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mihailov", "given" : "Evelin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moebus", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muhleisen", "given" : "Thomas W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muller-Nurasyid", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musk", "given" : "Bill", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Jiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakashima", "given" : "Eitaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Njolstad", "given" : "Inger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nothen", "given" : "Markus M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohnaka", "given" : "Keizo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Twee Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Kyong Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkin", "given" : "Melissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pechlivanis", "given" : "Sonali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl G P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Jackie F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rallidis", "given" : "Loukianos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossin", "given" : "Elizabeth J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saltevo", "given" : "Juha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saramies", "given" : "Jouko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segre", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shu", "given" : "Xiao Ou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigur[eth]sson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sivapalaratnam", "given" : "Suthesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "So", "given" : "Wing Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stancakova", "given" : "Alena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinbach", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syvanen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takayanagi", "given" : "Ryoichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teslovich", "given" : "Tanya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tikkanen", "given" : "Emmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trakalo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tremoli", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trip", "given" : "Mieke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Fuu Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valladares-Salgado", "given" : "Adan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vedantam", "given" : "Sailaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veglia", "given" : "Fabrizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Congrong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wennauer", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilsgaard", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiltshire", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winckler", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jer-Yuarn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Loic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokota", "given" : "Mitsuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabaneh", "given" : "Delilah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowden", "given" : "Donald W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Nancy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruz", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanis", "given" : "Craig L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jong-Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parra", "given" : "Esteban J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "3" ] ] }, "page" : "234-44", "publisher" : "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.", "title" : "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0024710", "ISSN" : "1932-6203", "PMID" : "21949744", "abstract" : "BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed \u03b2 values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (\u03b2\u200a=\u200a0.063 [95% CI: 0.013, 0.113] p\u200a=\u200a0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative \u03b2 value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p\u200a=\u200a1.29\u00d710(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p\u200a=\u200a9.1\u00d710(-4)) and 1.16 (95% CI: 1.05, 1.29; p\u200a=\u200a3.49\u00d710(-3)) respectively.\n\nCONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-3", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e24710", "title" : "Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1007/s00125-011-2063-2", "ISSN" : "1432-0428", "PMID" : "21350842", "abstract" : "AIMS/HYPOTHESIS: Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODS: Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur.\n\nRESULTS: SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 \u00d7 10(-12)), BMI (p = 2.25 \u00d7 10(-4)) and age at onset of diabetes (p = 0.002).\n\nCONCLUSIONS/INTERPRETATION: We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "1368-74", "title" : "Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1007/s00125-009-1595-1", "ISSN" : "1432-0428", "PMID" : "19937311", "abstract" : "AIMS/HYPOTHESIS: To test fasting glucose association at four loci recently identified or verified by genome-wide association (GWA) studies of European populations, we performed a replication study in two Asian populations.\n\nMETHODS: We genotyped five common variants previously reported in Europeans: rs1799884 (GCK), rs780094 (GCKR), rs560887 (G6PC2-ABCB11) and both rs1387153 and rs10830963 (MTNR1B) in the general Japanese (n = 4,813) and Sri Lankan (n = 2,319) populations. To identify novel variants, we further examined genetic associations near each locus by using GWA scan data on 776 non-diabetic Japanese samples.\n\nRESULTS: Fasting glucose association was replicated for the five single nucleotide polymorphisms (SNPs) at p < 0.05 (one-tailed test) in South Asians (Sri Lankan) as well as in East Asians (Japanese). In fine-mapping by GWA scan data, we identified in the G6PC2-ABCB11 region a novel SNP, rs3755157, with significant association in Japanese (p = 2.6 x 10(-8)) and Sri Lankan (p = 0.001) populations. The strength of association was more prominent at rs3755157 than that of the original SNP rs560887, with allelic heterogeneity detected between the SNPs. On analysing the cumulative effect of associated SNPs, we found the per-allele gradients (beta = 0.055 and 0.069 mmol/l in Japanese and Sri Lankans, respectively) to be almost equivalent to those reported in Europeans.\n\nCONCLUSIONS/INTERPRETATION: Fasting glucose association at four tested loci was proven to be replicable across ethnic groups. Despite this overall consistency, ethnic diversity in the pattern and strength of linkage disequilibrium certainly exists and can help to appreciably reduce potential causal variants after GWA studies.", "author" : [ { "dropping-particle" : "", "family" : "Takeuchi", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katsuya", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrewarthy", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fujioka", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serizawa", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fujisawa", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakashima", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohnaka", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikegami", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nabika", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasturiratne", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kono", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takayanagi", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamori", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogihara", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "A", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "299-308", "title" : "Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1007/s00125-012-2560-y", "ISSN" : "1432-0428", "PMID" : "22538361", "abstract" : "AIMS/HYPOTHESIS: Multiple genetic variants are associated with type 2 diabetes-related traits in Europeans, but their role in South Asian populations needs further study. We hypothesised that genetic variants associated with diabetes-related traits in Europeans would explain a similar proportion of phenotypic variance in a Pakistani population and could be used in Mendelian randomisation analyses.\n\nMETHODS: We used data from 2,131 individuals from the Control of Blood Pressure and Risk Attenuation Trial (COBRA) in Karachi, Pakistan. Individuals were aged 40 years or older.\n\nRESULTS: Combining information from multiple genetic variants showed that fasting glucose, BMI, triacylglycerol, and systolic and diastolic blood pressure variants explained 2.9%, 0.7%, 5.5%, 1.2% and 1.8% of the variance in those traits respectively. Genetic risk scores of fasting glucose, triacylglycerol, BMI, systolic blood pressure and diastolic blood pressure variants were associated with these traits, with per allele SD effects of 0.057 (95% CI 0.041, 0.074), p=3.44 \u00d7 10(-12), 0.130 (95% CI 0.105, 0.155), p=2.9 \u00d7 10(-21), 0.04 (95% CI 0.014, 0.072), p=0.004, 0.031 (95% CI 0.016, 0.047), p=7.9 \u00d7 10(-5), 0.028 (95% CI 0.015, 0.042), p = 5.5 \u00d7 10(-5), respectively. These effects are consistent with those observed in Europeans, except that the effect of triacylglycerol variants in South Asians was slightly lower. Mendelian randomisation provided evidence that genetically influenced, raised triacylglycerol levels do not causally affect type 2 diabetes risk to the extent predicted from observational data (p=0.0003 for difference between observed and instrumental variables correlations).\n\nCONCLUSIONS/INTERPRETATION: Genetic variants identified in Europeans are associated with type 2 diabetes-related traits in Pakistanis, with comparable effect sizes. Larger studies are needed to perform adequately powered Mendelian randomisation and help dissect the relationships between type 2 diabetes-related traits in diverse South Asian subgroups.", "author" : [ { "dropping-particle" : "", "family" : "Islam", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "N M G", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-6", "issue" : "8", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "2193-204", "title" : "Multiple genetic variants explain measurable variance in type 2 diabetes-related traits in Pakistanis.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "81,104,132,151\u2013153", "plainTextFormattedCitation" : "81,104,132,151\u2013153", "previouslyFormattedCitation" : "81,104,132,151\u2013153" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81,104,132,151–153. Four of the published studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0024710", "ISSN" : "1932-6203", "PMID" : "21949744", "abstract" : "BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed \u03b2 values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (\u03b2\u200a=\u200a0.063 [95% CI: 0.013, 0.113] p\u200a=\u200a0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative \u03b2 value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p\u200a=\u200a1.29\u00d710(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p\u200a=\u200a9.1\u00d710(-4)) and 1.16 (95% CI: 1.05, 1.29; p\u200a=\u200a3.49\u00d710(-3)) respectively.\n\nCONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e24710", "title" : "Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00125-011-2063-2", "ISSN" : "1432-0428", "PMID" : "21350842", "abstract" : "AIMS/HYPOTHESIS: Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODS: Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur.\n\nRESULTS: SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 \u00d7 10(-12)), BMI (p = 2.25 \u00d7 10(-4)) and age at onset of diabetes (p = 0.002).\n\nCONCLUSIONS/INTERPRETATION: We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "1368-74", "title" : "Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1007/s00125-009-1595-1", "ISSN" : "1432-0428", "PMID" : "19937311", "abstract" : "AIMS/HYPOTHESIS: To test fasting glucose association at four loci recently identified or verified by genome-wide association (GWA) studies of European populations, we performed a replication study in two Asian populations.\n\nMETHODS: We genotyped five common variants previously reported in Europeans: rs1799884 (GCK), rs780094 (GCKR), rs560887 (G6PC2-ABCB11) and both rs1387153 and rs10830963 (MTNR1B) in the general Japanese (n = 4,813) and Sri Lankan (n = 2,319) populations. To identify novel variants, we further examined genetic associations near each locus by using GWA scan data on 776 non-diabetic Japanese samples.\n\nRESULTS: Fasting glucose association was replicated for the five single nucleotide polymorphisms (SNPs) at p < 0.05 (one-tailed test) in South Asians (Sri Lankan) as well as in East Asians (Japanese). In fine-mapping by GWA scan data, we identified in the G6PC2-ABCB11 region a novel SNP, rs3755157, with significant association in Japanese (p = 2.6 x 10(-8)) and Sri Lankan (p = 0.001) populations. The strength of association was more prominent at rs3755157 than that of the original SNP rs560887, with allelic heterogeneity detected between the SNPs. On analysing the cumulative effect of associated SNPs, we found the per-allele gradients (beta = 0.055 and 0.069 mmol/l in Japanese and Sri Lankans, respectively) to be almost equivalent to those reported in Europeans.\n\nCONCLUSIONS/INTERPRETATION: Fasting glucose association at four tested loci was proven to be replicable across ethnic groups. Despite this overall consistency, ethnic diversity in the pattern and strength of linkage disequilibrium certainly exists and can help to appreciably reduce potential causal variants after GWA studies.", "author" : [ { "dropping-particle" : "", "family" : "Takeuchi", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katsuya", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrewarthy", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fujioka", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serizawa", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fujisawa", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakashima", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohnaka", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikegami", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sugiyama", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nabika", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasturiratne", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kono", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takayanagi", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamori", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobayashi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ogihara", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "A", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "299-308", "title" : "Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations.", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1007/s00125-012-2560-y", "ISSN" : "1432-0428", "PMID" : "22538361", "abstract" : "AIMS/HYPOTHESIS: Multiple genetic variants are associated with type 2 diabetes-related traits in Europeans, but their role in South Asian populations needs further study. We hypothesised that genetic variants associated with diabetes-related traits in Europeans would explain a similar proportion of phenotypic variance in a Pakistani population and could be used in Mendelian randomisation analyses.\n\nMETHODS: We used data from 2,131 individuals from the Control of Blood Pressure and Risk Attenuation Trial (COBRA) in Karachi, Pakistan. Individuals were aged 40 years or older.\n\nRESULTS: Combining information from multiple genetic variants showed that fasting glucose, BMI, triacylglycerol, and systolic and diastolic blood pressure variants explained 2.9%, 0.7%, 5.5%, 1.2% and 1.8% of the variance in those traits respectively. Genetic risk scores of fasting glucose, triacylglycerol, BMI, systolic blood pressure and diastolic blood pressure variants were associated with these traits, with per allele SD effects of 0.057 (95% CI 0.041, 0.074), p=3.44 \u00d7 10(-12), 0.130 (95% CI 0.105, 0.155), p=2.9 \u00d7 10(-21), 0.04 (95% CI 0.014, 0.072), p=0.004, 0.031 (95% CI 0.016, 0.047), p=7.9 \u00d7 10(-5), 0.028 (95% CI 0.015, 0.042), p = 5.5 \u00d7 10(-5), respectively. These effects are consistent with those observed in Europeans, except that the effect of triacylglycerol variants in South Asians was slightly lower. Mendelian randomisation provided evidence that genetically influenced, raised triacylglycerol levels do not causally affect type 2 diabetes risk to the extent predicted from observational data (p=0.0003 for difference between observed and instrumental variables correlations).\n\nCONCLUSIONS/INTERPRETATION: Genetic variants identified in Europeans are associated with type 2 diabetes-related traits in Pakistanis, with comparable effect sizes. Larger studies are needed to perform adequately powered Mendelian randomisation and help dissect the relationships between type 2 diabetes-related traits in diverse South Asian subgroups.", "author" : [ { "dropping-particle" : "", "family" : "Islam", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "N M G", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-4", "issue" : "8", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "2193-204", "title" : "Multiple genetic variants explain measurable variance in type 2 diabetes-related traits in Pakistanis.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "81,151\u2013153", "plainTextFormattedCitation" : "81,151\u2013153", "previouslyFormattedCitation" : "81,151\u2013153" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81,151–153 tested SNPs derived from white Caucasian populations on glucose and type 2 diabetes in various South Asian groups, including Pakistani, Sri Lankan, and South Indians. These SNP effects were then compared with literature-based estimates from white Caucasians. In a study from the UKADS/DGP cohorts, the South Asian estimate of glucose SNPs in 1,163 individuals were found to be similar to white Caucasians from the MAGIC consortium (n= 76,558)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0024710", "ISSN" : "1932-6203", "PMID" : "21949744", "abstract" : "BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed \u03b2 values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (\u03b2\u200a=\u200a0.063 [95% CI: 0.013, 0.113] p\u200a=\u200a0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative \u03b2 value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p\u200a=\u200a1.29\u00d710(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p\u200a=\u200a9.1\u00d710(-4)) and 1.16 (95% CI: 1.05, 1.29; p\u200a=\u200a3.49\u00d710(-3)) respectively.\n\nCONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e24710", "title" : "Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "151", "plainTextFormattedCitation" : "151", "previouslyFormattedCitation" : "151" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }151. Similarly, a study of type 2 diabetes genes compared 3,262 South Asians, again from the UKADS/DGP cohorts, to literature estimates from white Caucasian GWA-studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-011-2063-2", "ISSN" : "1432-0428", "PMID" : "21350842", "abstract" : "AIMS/HYPOTHESIS: Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODS: Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur.\n\nRESULTS: SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 \u00d7 10(-12)), BMI (p = 2.25 \u00d7 10(-4)) and age at onset of diabetes (p = 0.002).\n\nCONCLUSIONS/INTERPRETATION: We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "1368-74", "title" : "Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "81", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "81" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81, and reported homogeneity. As these were indirect comparisons with literature estimates, differences in ascertainment carry the potential to bias comparisons. However, an additional studyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2897", "ISSN" : "1546-1718", "PMID" : "24509480", "abstract" : "To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.", "author" : [ { "dropping-particle" : "", "family" : "DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "South Asian Type 2 Diabetes (SAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mexican American Type 2 Diabetes (MAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Go", "given" : "Min Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Below", "given" : "Jennifer E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horikoshi", "given" : "Momoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Maggie C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adair", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldassarre", "given" : "Damiano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bao", "given" : "Yuqian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "Graeme I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Qiuyin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carey", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "Juliana C N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Li-Ching", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Tien-Jyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yi-Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chien-Hsiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuan-Tsong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Nam H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Young Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chuang", "given" : "Lee-Ming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crenshaw", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donnelly", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorkhan", "given" : "Mozhgan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Josee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edkins", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erbel", "given" : "Raimund", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Escobedo", "given" : "Jorge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esko", "given" : "Tonu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eury", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontanillas", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsen", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraser", "given" : "Ross M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gao", "given" : "Yutang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gertow", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Bok-Ghee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmen", "given" : "Oddgeir L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hovingh", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hreidarsson", "given" : "Astradur B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunt", "given" : "Sarah E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikegami", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jia", "given" : "Weiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jockel", "given" : "Karl-Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Hyun Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen Hong L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "Ann M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Hassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hyung-Lae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Sangsoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Young Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinnunen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korpi-Hyovalti", "given" : "Eeva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kravic", "given" : "Jasmina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krithika", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Ashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumate", "given" : "Jesus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwak", "given" : "Soo Heon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langford", "given" : "Cordelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leander", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jen-Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Nanette R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindholm", "given" : "Eero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jian Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Long", "given" : "Jirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ma", "given" : "Ronald C W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mannisto", "given" : "Satu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metspalu", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mirza", "given" : "Ghazala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mihailov", "given" : "Evelin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moebus", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muhleisen", "given" : "Thomas W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muller-Nurasyid", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musk", "given" : "Bill", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Jiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakashima", "given" : "Eitaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Njolstad", "given" : "Inger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nothen", "given" : "Markus M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohnaka", "given" : "Keizo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Twee Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Kyong Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkin", "given" : "Melissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pechlivanis", "given" : "Sonali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl G P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Jackie F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rallidis", "given" : "Loukianos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossin", "given" : "Elizabeth J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saltevo", "given" : "Juha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saramies", "given" : "Jouko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segre", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shu", "given" : "Xiao Ou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigur[eth]sson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sivapalaratnam", "given" : "Suthesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "So", "given" : "Wing Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stancakova", "given" : "Alena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinbach", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syvanen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takayanagi", "given" : "Ryoichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teslovich", "given" : "Tanya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tikkanen", "given" : "Emmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trakalo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tremoli", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trip", "given" : "Mieke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Fuu Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valladares-Salgado", "given" : "Adan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vedantam", "given" : "Sailaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veglia", "given" : "Fabrizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Congrong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wennauer", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilsgaard", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiltshire", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winckler", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jer-Yuarn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Loic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokota", "given" : "Mitsuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabaneh", "given" : "Delilah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowden", "given" : "Donald W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Nancy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruz", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanis", "given" : "Craig L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jong-Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parra", "given" : "Esteban J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "3" ] ] }, "page" : "234-44", "publisher" : "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.", "title" : "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "104", "plainTextFormattedCitation" : "104", "previouslyFormattedCitation" : "104" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }104 performed a direct comparison of type 2 diabetes SNPs among white Caucasians and South Asians and again found similar effect sizes. There are a few key differences between our study and those previously conducted, which may explain why our results differ. Firstly, the EpiDREAM cohort included white Caucasians at a high-risk for developing diabetes, and thus differs from population-based cohorts included in GWA-studies and consortiums. Though some of these cohorts also investigate individuals at a high-risk for dysglycemia, a majority sample was from the general population or focused on other disease pathologiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "accessed" : { "date-parts" : [ [ "2015", "5", "18" ] ] }, "author" : [ { "dropping-particle" : "", "family" : "MAGIC Investigators", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "0" ] ] }, "title" : "MAGIC Cohorts", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "154", "plainTextFormattedCitation" : "154", "previouslyFormattedCitation" : "154" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }154. Second, the South Asians in our study are younger in age but with comparable BMI and baseline FPG than those from UKADS/DGP cohorts, and as such it is possible that the effect of a genetic load on glucose traits in this group varies from that reported in previous studies. Overall, among the high-risk individuals from the EpiDREAM cohort, genetics may play a greater role in South Asians than in white Caucasians, explaining why a greater effect on glucose traits is seen for this ethnic group. Third, unlike previous studies, we undertook a direct comparison of a genotype score, representing cumulative genetic burden, between South Asians and Caucasians.The genotype score is comprised of 11 SNPs that vary in their effect on glucose traits. The contribution of each SNP, as identified by published GWA-studies, is presented in Supplementary Table 3.2. Based on these estimates, it appears that among the 11 SNPs included, the two MTNR1B SNPs rs10830963 and rs2166706 and GCK rs4607517 has the biggest impact on fasting glucose. The genotypic effects of each SNP on glucose traits in both ethnicities are presented in Supplementary Table 3.3. However, it should be noted that the present analysis was underpowered; specifically, to detect an effect equivalent to the literature for GCK rs4607517, we had 74% power with a Bonferroni corrected type 1 error rate of 5%. 3.4.2 Ethnic heterogeneity in interaction of beta-cell genotype score with abdominal obesityGiven the strong relationship between abdominal obesity and dysglycemia, as well as its high prevalence among South Asians, we assessed if the impact of the beta-cell genotype score on glucose traits was accentuated by the presence of abdominal obesity, and whether this varied by ethnicity. Since a three-way interaction between ethnicity, abdominal obesity, and the genotype score was significant for both glucose traits, the interaction of abdominal obesity with genotype score was investigated separately for South Asians and white Caucasians. The findings showed a positive interaction of abdominal obesity (measured by WaistadjHip) with beta-cell genotype score on AUC glucose and fasting glucose in South Asians, but not in white Caucasians. This suggests that South Asians experience a greater impact on glucose levels of the genetic load of beta cell impairment as they become more abdominally obese.A possible explanation for this observation may be that South Asians experience greater functional beta-cell impairment from glucolipotoxicityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2012/386041", "ISSN" : "1687-5303", "PMID" : "23304116", "abstract" : "AIM: An exploration of ethnic differences in measures of oxidative stress and endothelial activation in relation to known cardiovascular risk factors within South Asians (SA) and White Europeans (WE) residing in the UK.\n\nMETHODS: 202 participants within a UK multiethnic population provided biomedical and anthropometric data. Human urinary 2,3-dinor-8-iso-prostaglandin-F1\u03b1 and plasma ICAM-1 were quantified as measures of oxidative stress and endothelial activation, respectively.\n\nRESULTS: 2,3-Dinor-8-iso-prostaglandin-F1\u03b1 levels were significantly higher in the SA group compared to WE group (10.36 (95% CI: 9.09, 11.79) versus 8.46 (7.71, 9.29), P = 0.021) after adjustment for age, gender, smoking status, body weight, HbA1c, and medication. Oxidative stress was positively associated with HbA1c (\u03b2 = 1.08, 95% CI:1.02, 1.14, P = 0.009), fasting (\u03b2 = 1.06, 95% CI: 1.02, 1.10, P = 0.002), and 2 hr glucose (\u03b2 = 1.02, 95% CI: 1.00, 1.04, P = 0.052). In each adjusted model, SA continued to have elevated levels of oxidative stress compared to WE. ICAM-1 levels were significantly higher in the composite IGR group compared to the normoglycaemic group (P < 0.001). No ethnic differences in ICAM-1 were observed.\n\nCONCLUSION: These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted.", "author" : [ { "dropping-particle" : "", "family" : "Brady", "given" : "E M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Webb", "given" : "D R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "D H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khunti", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talbot", "given" : "D S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sattar", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Experimental diabetes research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "386041", "title" : "Investigating endothelial activation and oxidative stress in relation to glycaemic control in a multiethnic population.", "type" : "article-journal", "volume" : "2012" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/en.2003-0410", "ISSN" : "0013-7227", "PMID" : "12933690", "abstract" : "We have proposed the \"glucolipotoxicity\" hypothesis in which elevated free fatty acids (FFAs) together with hyperglycemia are synergistic in causing islet beta-cell damage because high glucose inhibits fat oxidation and consequently lipid detoxification. The effects of 1-2 d culture of both rat INS 832/13 cells and human islet beta-cells were investigated in medium containing glucose (5, 11, 20 mM) in the presence or absence of various FFAs. A marked synergistic effect of elevated concentrations of glucose and saturated FFA (palmitate and stearate) on inducing beta-cell death by apoptosis was found in both INS 832/13 and human islet beta-cells. In comparison, linoleate (polyunsaturated) synergized only modestly with high glucose, whereas oleate (monounsaturated) was not toxic. Treating cells with the acyl-coenzyme A synthase inhibitor triacsin C, or the AMP kinase activators metformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside that redirect lipid partitioning to oxidation, curtailed glucolipotoxicity. In contrast, the fat oxidation inhibitor etomoxir, like glucose, markedly enhanced palmitate-induced cell death. The data indicate that FFAs must be metabolized to long chain fatty acyl-CoA to exert toxicity, the effect of which can be reduced by activating fatty acid oxidation. The results support the glucolipotoxicity hypothesis of beta-cell failure proposing that elevated FFAs are particularly toxic in the context of hyperglycemia.", "author" : [ { "dropping-particle" : "", "family" : "El-Assaad", "given" : "Wissal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buteau", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peyot", "given" : "Marie-Line", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nolan", "given" : "Christopher", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roduit", "given" : "Raphael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hardy", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joly", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dbaibo", "given" : "Ghassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenberg", "given" : "Lawrence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prentki", "given" : "Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrinology", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "4154-63", "title" : "Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death.", "type" : "article-journal", "volume" : "144" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1210/er.2007-0023", "ISSN" : "0163-769X", "PMID" : "18048763", "abstract" : "Glucotoxicity, lipotoxicity, and glucolipotoxicity are secondary phenomena that are proposed to play a role in all forms of type 2 diabetes. The underlying concept is that once the primary pathogenesis of diabetes is established, probably involving both genetic and environmental forces, hyperglycemia and very commonly hyperlipidemia ensue and thereafter exert additional damaging or toxic effects on the beta-cell. In addition to their contribution to the deterioration of beta-cell function after the onset of the disease, elevations of plasma fatty acid levels that often accompany insulin resistance may, as glucose levels begin to rise outside of the normal range, also play a pathogenic role in the early stages of the disease. Because hyperglycemia is a prerequisite for lipotoxicity to occur, the term glucolipotoxicity, rather than lipotoxicity, is more appropriate to describe deleterious effects of lipids on beta-cell function. In vitro and in vivo evidence supporting the concept of glucotoxicity is presented first, as well as a description of the underlying mechanisms with an emphasis on the role of oxidative stress. Second, we discuss the functional manifestations of glucolipotoxicity on insulin secretion, insulin gene expression, and beta-cell death, and the role of glucose in the mechanisms of glucolipotoxicity. Finally, we attempt to define the role of these phenomena in the natural history of beta-cell compensation, decompensation, and failure during the course of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Poitout", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "R Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrine reviews", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2008", "5" ] ] }, "page" : "351-66", "title" : "Glucolipotoxicity: fuel excess and beta-cell dysfunction.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "131,155,156", "plainTextFormattedCitation" : "131,155,156", "previouslyFormattedCitation" : "131,155,156" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }131,155,156. Comparison of anthropometric profiles, MRI measurement of abdominal fat, and MR spectroscopy of the liver indicate that when matched by BMI, South Asians have more deep superficial subcutaneous and visceral adipose tissue, and more ectopic fat deposition in the liverADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0022112", "ISSN" : "1932-6203", "PMID" : "21829446", "abstract" : "OBJECTIVE: We sought to determine if differences in the distribution and characteristics of adipose tissue between South Asians and white Caucasians account for differences in risk factors for cardiovascular disease.\n\nRESEARCH DESIGN AND METHODS: We recruited 108 healthy South Asians (36.8 years) and white Caucasians (34.2 years) within three BMI strata. Body composition, adipocyte size, abdominal fat area, and hepatic adiposity were assessed and related to fasting glucose, insulin, lipids and adiponectin.\n\nRESULTS: After adjustment for age, sex, and BMI, South Asians compared to white Caucasians had higher ln fasting insulin (mean difference (MD): 0.44; 95% CI: 0.20-0.69), lower HDL cholesterol (md: -0.13; 95% CI:-0.26 to -0.01), and lower adiponectin (md: -2.38; 95% CI: -3.59 to -1.17). South Asians also had more body fat (md: 2.69; 95% CI: 0.70 to 4.69), lower lean muscle mass (md: -3.25; 95%CI: -5.35 to -1.14), increased waist to hip ratio (md: 0.03; 95% CI: 0.01-0.05), less superficial subcutaneous abdominal adipose tissue (md: -2.94; 95% CI: -5.56 to-0.32), more deep/visceral to superficial adipose tissue ratio (md 0.34; 95% CI: 0.02 to 0.65), and more liver fat (md: 7.43%; 95% CI: 2.30 to 12.55%). Adipocyte area was increased in South Asians compared to white Caucasians (md: 64.26; 95% CI: 24.3 to 104.1) units(2). Adjustment for adipocyte area attenuated the ethnic differences in insulin (md: 0.22; 95% CI: -0.07 to 0.51), HDL (md: -0.01; 95% CI: -0.16 to 0.13) and adiponectin (md: -1.11; 95% CI: -2.61 to 0.39). Adjustment for differences in adipocyte area and fat distribution attenuated the ethnic difference in liver fat (md: 5.19; 95% CI: 0.31 to 10.06).\n\nCONCLUSION: South Asians have an increased adipocyte area compared to white Caucasians. This difference accounts for the ethnic differences in insulin, HDL cholesterol, adiponectin, and ectopic fat deposition in the liver.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarnopolsky", "given" : "Mark A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rashid", "given" : "Shirya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schulze", "given" : "Karleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mente", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Sandy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Arya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Stanojevic", "given" : "Sanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e22112", "publisher" : "Public Library of Science", "title" : "Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE).", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jcem.84.7.5817", "ISSN" : "0021-972X", "PMID" : "10404798", "abstract" : "It has been proposed that excessive insulin resistance in Asian Indians living in urban areas or migrated to western countries is responsible for the higher incidence of type 2 diabetes and coronary heart disease observed in this population. To evaluate whether Asian Indians are more insulin resistant than Caucasians and to define the role of generalized and truncal adiposity, we performed hydrodensitometry, skinfold measurements, and euglycemic-hyperinsulinemic clamps in 21 healthy Asian Indian men and 23 Caucasian men of similar age and body fat content. The glucose disposal rate (Rd) was significantly lower in the Asian Indians than in the Caucasians (3.7+/-1.3 vs. 5.3+/-2.0 mg/min x kg lean body mass, respectively; P = 0.003). Despite similar total body fat content, Asian Indians had higher truncal adiposity than Caucasians (sum of truncal skinfolds, 117+/-37 and 92.4+/-38 mm, respectively). In both Asian Indians and Caucasians, the insulin sensitivity index (Rd/plasma insulin concentrations) was inversely correlated with both total body fat (r = -0.49; P<0.03 and r = -0.67; P<0.001, respectively) and sum of truncal skinfold thickness (r = -0.55; P<0.001 and r = -0.61; P<0.002, respectively). After adjustment for total body fat and truncal skinfold thickness, Asian Indians still had a significantly lower glucose disposal rate (P = 0.04). These results show that Asian Indian men are more insulin resistant than Caucasian men independently of generalized or truncal adiposity. The excessive insulin resistance in Asian Indians is probably a primary metabolic defect and may account for the excessive morbidity and mortality from diabetes and coronary heart disease in this population.", "author" : [ { "dropping-particle" : "", "family" : "Chandalia", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abate", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garg", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stray-Gundersen", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "1999", "7" ] ] }, "page" : "2329-35", "title" : "Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men.", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0899-9007", "PMID" : "12921898", "author" : [ { "dropping-particle" : "", "family" : "Misra", "given" : "Anoop", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nutrition (Burbank, Los Angeles County, Calif.)", "id" : "ITEM-3", "issue" : "9", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "815-6", "title" : "Impact of ethnicity on body fat patterning in Asian Indians and blacks: relation with insulin resistance.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "39,134,135", "plainTextFormattedCitation" : "39,134,135", "previouslyFormattedCitation" : "39,134,135" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39,134,135 than do white Caucasians. These differences are associated with greater dyslipidemia, lower adiponectin, and lowered insulin sensitivity in South AsiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/0140-6736(91)91164-P", "ISSN" : "01406736", "abstract" : "The hypothesis that the high mortality from coronary heart disease (CHD) in South Asians settled overseas compared with other populations is due to metabolic disturbances related to insulin resistance was tested in a population survey of 3193 men and 561 women aged 40-69 years in London, UK. The sample was assembled from industrial workforces and general practitioners' lists. In comparison with the European group, the South Asian group had a higher prevalence of diabetes (19% vs 4%), higher blood pressures, higher fasting and post-glucose serum insulin concentrations, higher plasma triglyceride. and lower HDL cholesterol concentrations. Mean waist-hip girth ratios and trunk skinfolds were higher in the South Asian than in the European group. Within each ethnic group waist-hip ratio was correlated with glucose intolerance, insulin, blood pressure, and triglyceride. These results confirm the existence of an insulin resistance syndrome, prevalent in South Asian populations and associated with a pronounced tendency to central obesity in this group. Control of obesity and greater physical activity offer the best chances for prevention of diabetes and CHD in South Asian people.", "author" : [ { "dropping-particle" : "", "family" : "McKeigue", "given" : "P.M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "M.G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet", "id" : "ITEM-1", "issue" : "8738", "issued" : { "date-parts" : [ [ "1991", "2", "16" ] ] }, "page" : "382-386", "title" : "Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians", "type" : "article-journal", "volume" : "337" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0022112", "ISSN" : "1932-6203", "PMID" : "21829446", "abstract" : "OBJECTIVE: We sought to determine if differences in the distribution and characteristics of adipose tissue between South Asians and white Caucasians account for differences in risk factors for cardiovascular disease.\n\nRESEARCH DESIGN AND METHODS: We recruited 108 healthy South Asians (36.8 years) and white Caucasians (34.2 years) within three BMI strata. Body composition, adipocyte size, abdominal fat area, and hepatic adiposity were assessed and related to fasting glucose, insulin, lipids and adiponectin.\n\nRESULTS: After adjustment for age, sex, and BMI, South Asians compared to white Caucasians had higher ln fasting insulin (mean difference (MD): 0.44; 95% CI: 0.20-0.69), lower HDL cholesterol (md: -0.13; 95% CI:-0.26 to -0.01), and lower adiponectin (md: -2.38; 95% CI: -3.59 to -1.17). South Asians also had more body fat (md: 2.69; 95% CI: 0.70 to 4.69), lower lean muscle mass (md: -3.25; 95%CI: -5.35 to -1.14), increased waist to hip ratio (md: 0.03; 95% CI: 0.01-0.05), less superficial subcutaneous abdominal adipose tissue (md: -2.94; 95% CI: -5.56 to-0.32), more deep/visceral to superficial adipose tissue ratio (md 0.34; 95% CI: 0.02 to 0.65), and more liver fat (md: 7.43%; 95% CI: 2.30 to 12.55%). Adipocyte area was increased in South Asians compared to white Caucasians (md: 64.26; 95% CI: 24.3 to 104.1) units(2). Adjustment for adipocyte area attenuated the ethnic differences in insulin (md: 0.22; 95% CI: -0.07 to 0.51), HDL (md: -0.01; 95% CI: -0.16 to 0.13) and adiponectin (md: -1.11; 95% CI: -2.61 to 0.39). Adjustment for differences in adipocyte area and fat distribution attenuated the ethnic difference in liver fat (md: 5.19; 95% CI: 0.31 to 10.06).\n\nCONCLUSION: South Asians have an increased adipocyte area compared to white Caucasians. This difference accounts for the ethnic differences in insulin, HDL cholesterol, adiponectin, and ectopic fat deposition in the liver.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarnopolsky", "given" : "Mark A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rashid", "given" : "Shirya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schulze", "given" : "Karleen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mente", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Sandy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Arya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Stanojevic", "given" : "Sanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e22112", "publisher" : "Public Library of Science", "title" : "Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE).", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "39,157", "plainTextFormattedCitation" : "39,157", "previouslyFormattedCitation" : "39,157" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }39,157. In vivo and in vitro studies have demonstrated that excess fatty acids in the presence of hyperglycemia causes glucolipotoxicity by impairing gene expressionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0026-0495", "PMID" : "10778881", "abstract" : "Long-term exposure of pancreatic beta cells to elevated levels of fatty acids (FAs) impairs glucose-induced insulin secretion. However, the effects of FAs on insulin gene expression are controversial. We hypothesized that FAs adversely affect insulin gene expression only in the presence of elevated glucose concentrations. To test this hypothesis, isolated rat islets were cultured for up to 1 week in the presence of 2.8 or 16.7 mmol/L glucose with or without 0.5 mmol/L palmitate. Insulin release, insulin content, and insulin mRNA levels were determined at the end of each culture period. Palmitate increased insulin release at each time point independently of the glucose concentration. In contrast, insulin content was unchanged in the presence of palmitate at 2.8 mmol/L glucose, but was markedly decreased in the presence of 0.5 mmol/L palmitate and 16.7 mmol/L glucose after 2, 3, and 7 days of culture. In the presence of a basal concentration of glucose, insulin mRNA levels were transiently increased by palmitate at 24 hours but were unchanged thereafter. In contrast, palmitate significantly inhibited the stimulatory effects of 16.7 mmol/L glucose on insulin mRNA levels after 2, 3, and 7 days. To determine whether the inhibitory effect of palmitate on glucose-stimulated insulin mRNA levels was associated with decreased insulin promoter activity, HIT-T15 cells were cultured for 24 hours in 11.1 mmol/L glucose in the presence or absence of palmitate, and insulin gene promoter activity was measured in transient transfection experiments using the insulin promoter-reporter construct INSLUC. INSLUC activity was decreased more than 2-fold after 24 hours of exposure to 0.5 mmol/L palmitate. We conclude that long-term exposure of pancreatic beta cells to palmitate decreases insulin gene expression only in the presence of elevated glucose concentrations, in part through inhibition of insulin gene promoter activity.", "author" : [ { "dropping-particle" : "", "family" : "Jacqueminet", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Briaud", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rouault", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reach", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poitout", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2000", "4" ] ] }, "page" : "532-6", "title" : "Inhibition of insulin gene expression by long-term exposure of pancreatic beta cells to palmitate is dependent on the presence of a stimulatory glucose concentration.", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "158", "plainTextFormattedCitation" : "158", "previouslyFormattedCitation" : "158" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }158, inducing beta-cell deathADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/en.2003-0410", "ISSN" : "0013-7227", "PMID" : "12933690", "abstract" : "We have proposed the \"glucolipotoxicity\" hypothesis in which elevated free fatty acids (FFAs) together with hyperglycemia are synergistic in causing islet beta-cell damage because high glucose inhibits fat oxidation and consequently lipid detoxification. The effects of 1-2 d culture of both rat INS 832/13 cells and human islet beta-cells were investigated in medium containing glucose (5, 11, 20 mM) in the presence or absence of various FFAs. A marked synergistic effect of elevated concentrations of glucose and saturated FFA (palmitate and stearate) on inducing beta-cell death by apoptosis was found in both INS 832/13 and human islet beta-cells. In comparison, linoleate (polyunsaturated) synergized only modestly with high glucose, whereas oleate (monounsaturated) was not toxic. Treating cells with the acyl-coenzyme A synthase inhibitor triacsin C, or the AMP kinase activators metformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside that redirect lipid partitioning to oxidation, curtailed glucolipotoxicity. In contrast, the fat oxidation inhibitor etomoxir, like glucose, markedly enhanced palmitate-induced cell death. The data indicate that FFAs must be metabolized to long chain fatty acyl-CoA to exert toxicity, the effect of which can be reduced by activating fatty acid oxidation. The results support the glucolipotoxicity hypothesis of beta-cell failure proposing that elevated FFAs are particularly toxic in the context of hyperglycemia.", "author" : [ { "dropping-particle" : "", "family" : "El-Assaad", "given" : "Wissal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buteau", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peyot", "given" : "Marie-Line", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nolan", "given" : "Christopher", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roduit", "given" : "Raphael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hardy", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joly", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dbaibo", "given" : "Ghassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosenberg", "given" : "Lawrence", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prentki", "given" : "Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrinology", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "4154-63", "title" : "Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death.", "type" : "article-journal", "volume" : "144" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "156", "plainTextFormattedCitation" : "156", "previouslyFormattedCitation" : "156" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }156, and reducing insulin secretion from existing islet cellsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jcem.80.5.7745004", "ISSN" : "0021-972X", "PMID" : "7745004", "abstract" : "We previously demonstrated in the rat that long term exposure to fatty acids inhibits B-cell function in vivo and in vitro. To further assess the clinical significance of these findings, we tested in human islets the effects of fatty acids on glucose-induced insulin release and biosynthesis and on pyruvate dehydrogenase (PDH) activity. Human islets were obtained from the beta-Cell Transplant Unit (Brussels, Belgium). Exposure to 0.125 mmol/L palmitate or oleate for 48 h during tissue culture (RPMI-1640 and 5.5 mmol/L glucose) inhibited the postculture insulin response to 27 mmol/L glucose by 40% and 42% (P < 0.01 for difference). Inhibition was partly prevented by coculture with 1 mumol/L etomoxir, a carnitine-palmitoyl-transferase-I inhibitor (P < 0.05 for effect of etomoxir). Inhibitory effects on glucose-induced insulin secretion by previous palmitate were additive to the inhibitory effects exerted by previous high glucose (11 and 27 mmol/L). Palmitate-induced inhibition of insulin secretion was evident after exposure to 25 mumol/L added fatty acid. The insulin content of islets exposed to fatty acids was significantly reduced, and glucose-induced proinsulin biosynthesis was inhibited by 59% after palmitate addition and by 51% after oleate exposure (P < 0.01). These effects were partly prevented by etomoxir (P < 0.05). The activity of PDH in mitochondrial extracts of islets preexposed for 48 h to palmitate was decreased by 35% (P < 0.05) vs. that in control islets, whereas the activity of PDH kinase (which inactivates PDH) was significantly increased in the same preparations (P < 0.05). The effects of ketones were tested by 48-h exposure to beta-hydroxybutyrate (beta-D-OHB). Ten millimoles of D-beta-OHB per L inhibited the subsequently tested insulin response to 27 mmol/L glucose by 56% (P < 0.001). Half-maximal inhibitory effects of D-beta-OHB on insulin secretion and insulin content were seen at concentrations between 0.5-2.5 mmol/L. Inhibition by D-beta-OHB was partially reversed by etomoxir, whereas exposure to D-beta-OHB failed to affect PDH and PDH kinase activities. We conclude that fatty acids as well as ketone bodies diminish B-cell responsiveness to glucose in human islets by way of a glucose-fatty acid cycle. Increased plasma concentrations of fatty acids and ketones are likely to be important factors behind the negative influences on B-cell function exerted by a diabetic state in both type 1 and type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Zhou", "given" : "Y P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grill", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "5" ] ] }, "page" : "1584-90", "title" : "Long term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "159", "plainTextFormattedCitation" : "159", "previouslyFormattedCitation" : "159" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }159. Because white Caucasians can expand fat stores in superficial and deep subcutaneous regions, they may be less susceptible to glucolipotoxicityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2012/386041", "ISSN" : "1687-5303", "PMID" : "23304116", "abstract" : "AIM: An exploration of ethnic differences in measures of oxidative stress and endothelial activation in relation to known cardiovascular risk factors within South Asians (SA) and White Europeans (WE) residing in the UK.\n\nMETHODS: 202 participants within a UK multiethnic population provided biomedical and anthropometric data. Human urinary 2,3-dinor-8-iso-prostaglandin-F1\u03b1 and plasma ICAM-1 were quantified as measures of oxidative stress and endothelial activation, respectively.\n\nRESULTS: 2,3-Dinor-8-iso-prostaglandin-F1\u03b1 levels were significantly higher in the SA group compared to WE group (10.36 (95% CI: 9.09, 11.79) versus 8.46 (7.71, 9.29), P = 0.021) after adjustment for age, gender, smoking status, body weight, HbA1c, and medication. Oxidative stress was positively associated with HbA1c (\u03b2 = 1.08, 95% CI:1.02, 1.14, P = 0.009), fasting (\u03b2 = 1.06, 95% CI: 1.02, 1.10, P = 0.002), and 2 hr glucose (\u03b2 = 1.02, 95% CI: 1.00, 1.04, P = 0.052). In each adjusted model, SA continued to have elevated levels of oxidative stress compared to WE. ICAM-1 levels were significantly higher in the composite IGR group compared to the normoglycaemic group (P < 0.001). No ethnic differences in ICAM-1 were observed.\n\nCONCLUSION: These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted.", "author" : [ { "dropping-particle" : "", "family" : "Brady", "given" : "E M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Webb", "given" : "D R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "D H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khunti", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talbot", "given" : "D S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sattar", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Experimental diabetes research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "386041", "title" : "Investigating endothelial activation and oxidative stress in relation to glycaemic control in a multiethnic population.", "type" : "article-journal", "volume" : "2012" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "155", "plainTextFormattedCitation" : "155", "previouslyFormattedCitation" : "155" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }155 than South Asians. Congruent with this, a mechanistic study comparing human urinary 2,3-dinor-8- iso-prostaglandin-F1α and plasma Intercellular Adhesion Molecule 1 (ICAM-1), measures of oxidative stress, in South Asians and Caucasians found that the former are more susceptible to the detrimental effects of oxidative stress on pancreatic beta-cells, a contributing factor to glucolipotoxicity, from hyperglycaemia at lower glucose thresholdsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2012/386041", "ISSN" : "1687-5303", "PMID" : "23304116", "abstract" : "AIM: An exploration of ethnic differences in measures of oxidative stress and endothelial activation in relation to known cardiovascular risk factors within South Asians (SA) and White Europeans (WE) residing in the UK.\n\nMETHODS: 202 participants within a UK multiethnic population provided biomedical and anthropometric data. Human urinary 2,3-dinor-8-iso-prostaglandin-F1\u03b1 and plasma ICAM-1 were quantified as measures of oxidative stress and endothelial activation, respectively.\n\nRESULTS: 2,3-Dinor-8-iso-prostaglandin-F1\u03b1 levels were significantly higher in the SA group compared to WE group (10.36 (95% CI: 9.09, 11.79) versus 8.46 (7.71, 9.29), P = 0.021) after adjustment for age, gender, smoking status, body weight, HbA1c, and medication. Oxidative stress was positively associated with HbA1c (\u03b2 = 1.08, 95% CI:1.02, 1.14, P = 0.009), fasting (\u03b2 = 1.06, 95% CI: 1.02, 1.10, P = 0.002), and 2 hr glucose (\u03b2 = 1.02, 95% CI: 1.00, 1.04, P = 0.052). In each adjusted model, SA continued to have elevated levels of oxidative stress compared to WE. ICAM-1 levels were significantly higher in the composite IGR group compared to the normoglycaemic group (P < 0.001). No ethnic differences in ICAM-1 were observed.\n\nCONCLUSION: These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted.", "author" : [ { "dropping-particle" : "", "family" : "Brady", "given" : "E M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Webb", "given" : "D R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "D H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khunti", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talbot", "given" : "D S C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sattar", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Experimental diabetes research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "386041", "title" : "Investigating endothelial activation and oxidative stress in relation to glycaemic control in a multiethnic population.", "type" : "article-journal", "volume" : "2012" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "155", "plainTextFormattedCitation" : "155", "previouslyFormattedCitation" : "155" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }155.Moreover, using whole genome sequencing Chambers et al recently demonstrated divergence in risk allele frequency in South Asians for genes involved in metabolism and energy storage compared to white Caucasians. This whole genome analysis provides support for variation in the metabolic process among ethnic groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0102645", "ISSN" : "1932-6203", "PMID" : "25115870", "abstract" : "The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.", "author" : [ { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turro", "given" : "Ernest", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "William R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "Sian-Tsung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afzal", "given" : "Uzma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afaq", "given" : "Saima", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehne", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Reilly", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lavery", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandrovcova", "given" : "Jana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wass", "given" : "Mark N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Kathryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oozageer", "given" : "Laticia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Ishminder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Hussaini", "given" : "Abtehale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mills", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grewal", "given" : "Jagvir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Panoulas", "given" : "Vasileios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewin", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Northwood", "given" : "Korrinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geoghegan", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yingrui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aitman", "given" : "Timothy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butcher", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "1", "12" ] ] }, "page" : "e102645", "title" : "The South Asian genome.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "108", "plainTextFormattedCitation" : "108", "previouslyFormattedCitation" : "108" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }108 and also supports the possibility of novel, yet unexplored genetic variants that contribute to the divergent risk for hyperglycemia and the metabolic syndrome. While not exhaustive, some evidence supports presence of exclusive genetic correlates for components of metabolic syndrome in South AsiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2003-030453", "ISSN" : "0021-972X", "PMID" : "14671192", "abstract" : "Genetic susceptibility may be responsible for high prevalence of insulin resistance in Asian Indians. This study was carried out in samples of local Asian Indians and Caucasians to determine whether plasma cell membrane glycoprotein (PC)-1 K121Q and insulin receptor substrate-1 (IRS-1) G972A polymorphisms contribute significantly to susceptibility to insulin resistance in Asian Indians. The frequency of carrying at least one copy of the PC-1 121Q variant in Asian Indians was significantly higher than that in Caucasians (P = 0.01), but the frequency was similar for IRS-1 972A (6% and 7%). A significantly higher insulin area under the curve during oral glucose tolerance testing (P < 0.0001) and lower insulin sensitivity during hyperinsulinemic-euglycemic clamps (P = 0.04) were found in Asian Indians with PC-1 121Q variant compared with Asian Indians with wild-type PC-1 and with Caucasians with or without the polymorphism. IRS-1 972A was not associated with any change in insulin sensitivity. We conclude that the PC-1 K121Q polymorphism associates with primary insulin resistance in migrant Asian Indians. A relatively high frequency of this polymorphism thus may be one factor contributing to insulin resistance susceptibility in Asian Indians. This finding indicates the need for expanded studies on the association between PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Abate", "given" : "Nicola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carulli", "given" : "Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cabo-Chan", "given" : "Alberto", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandalia", "given" : "Manisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Snell", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2003", "12", "2" ] ] }, "language" : "en", "page" : "5927-34", "publisher" : "Endocrine Society", "title" : "Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2004-1338", "ISSN" : "0021-972X", "PMID" : "15598690", "abstract" : "The Chennai Urban Population Study investigates a South Indian population with a high prevalence of cardiovascular disease associated with the metabolic syndrome (MS). The Ala54Thr polymorphism in the fatty acid-binding protein 2 (FABP2) gene as well as the T-455C and C-482T polymorphisms in the apolipoprotein C-III (APOC3) gene promoter have been associated with features of the MS in specific populations. This study evaluates in Asian-Indians the association between these polymorphisms with MS and dyslipidemia, defined according to National Cholesterol Education Program Adult Treatment Panel III. Allelic frequencies in 70 controls and 110 patients with diabetes from the Chennai Urban Population Study were 52.9% for FABP2 Thr54, 73.0% for APOC3 -482T, and 80.2% for APOC3 -455C. The polymorphisms were in agreement with Hardy-Weinberg equilibrium. Controls carrying FABP2 Thr54 were more likely to have MS than noncarriers (Fisher's exact test P = 0.031; odds ratio = 6.9 with a 95% confidence interval of 1.1, 43.9). Those carrying at least one polymorphic allele in both genes had a higher likelihood of having MS than wild type (Fisher's exact test P = 0.003; odds ratio = 12.1 with a 95% confidence interval of 1.88, 77.6). Dyslipidemia was associated with the polymorphism as well. The polymorphisms were not associated with MS in patients with diabetes. The association of the polymorphisms with MS and dyslipidemia could contribute to the high cardiovascular disease prevalence in this population.", "author" : [ { "dropping-particle" : "", "family" : "Guettier", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Georgopoulos", "given" : "Angeliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Michael Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shanthirani", "given" : "Subramaniam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deepa", "given" : "Raj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gross", "given" : "Myron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Gundu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2005", "3" ] ] }, "page" : "1705-11", "title" : "Polymorphisms in the fatty acid-binding protein 2 and apolipoprotein C-III genes are associated with the metabolic syndrome and dyslipidemia in a South Indian population.", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1073/pnas.1410428111", "ISSN" : "1091-6490", "PMID" : "25157153", "abstract" : "Peroxisome proliferator-activated receptor gamma (PPARG) is a master transcriptional regulator of adipocyte differentiation and a canonical target of antidiabetic thiazolidinedione medications. In rare families, loss-of-function (LOF) mutations in PPARG are known to cosegregate with lipodystrophy and insulin resistance; in the general population, the common P12A variant is associated with a decreased risk of type 2 diabetes (T2D). Whether and how rare variants in PPARG and defects in adipocyte differentiation influence risk of T2D in the general population remains undetermined. By sequencing PPARG in 19,752 T2D cases and controls drawn from multiple studies and ethnic groups, we identified 49 previously unidentified, nonsynonymous PPARG variants (MAF < 0.5%). Considered in aggregate (with or without computational prediction of functional consequence), these rare variants showed no association with T2D (OR = 1.35; P = 0.17). The function of the 49 variants was experimentally tested in a novel high-throughput human adipocyte differentiation assay, and nine were found to have reduced activity in the assay. Carrying any of these nine LOF variants was associated with a substantial increase in risk of T2D (OR = 7.22; P = 0.005). The combination of large-scale DNA sequencing and functional testing in the laboratory reveals that approximately 1 in 1,000 individuals carries a variant in PPARG that reduces function in a human adipocyte differentiation assay and is associated with a substantial risk of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Majithia", "given" : "Amit R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flannick", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shahinian", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guo", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bray", "given" : "Mark-Anthony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontanillas", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabriel", "given" : "Stacey B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosen", "given" : "Evan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Proceedings of the National Academy of Sciences of the United States of America", "id" : "ITEM-3", "issue" : "36", "issued" : { "date-parts" : [ [ "2014", "9", "9" ] ] }, "page" : "13127-32", "title" : "Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes.", "type" : "article-journal", "volume" : "111" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "160\u2013162", "plainTextFormattedCitation" : "160\u2013162", "previouslyFormattedCitation" : "160\u2013162" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }160–162. Future investigation of novel SNPs and insertion/deletion polymorphisms involved in storage and metabolism may help explain the divergent metabolic phenotype of South Asians, including variation in deposition of fat as well as adipocyte cell size and type, and may further explain the interaction between abdominal adiposity and beta cell function observed in this high risk ethnic group.3.4.3 Population stratification and inbreedingPopulation stratification was assessed using PCA as outlined by Price and colleaguesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng1847", "ISSN" : "1061-4036", "PMID" : "16862161", "abstract" : "Population stratification--allele frequency differences between cases and controls due to systematic ancestry differences-can cause spurious associations in disease studies. We describe a method that enables explicit detection and correction of population stratification on a genome-wide scale. Our method uses principal components analysis to explicitly model ancestry differences between cases and controls. The resulting correction is specific to a candidate marker's variation in frequency across ancestral populations, minimizing spurious associations while maximizing power to detect true associations. Our simple, efficient approach can easily be applied to disease studies with hundreds of thousands of markers.", "author" : [ { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plenge", "given" : "Robert M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinblatt", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shadick", "given" : "Nancy A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2006", "8" ] ] }, "page" : "904-9", "title" : "Principal components analysis corrects for stratification in genome-wide association studies.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "140", "plainTextFormattedCitation" : "140", "previouslyFormattedCitation" : "140" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }140. Our results suggest that within the South Asian and white Caucasian groups from the EpiDREAM cohort, there is no evidence of population substructure. It should be noted that the 50K IBC array is designed with admixture and ancestry informed markers for only European and American Caucasians as well as African American groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0003583", "ISSN" : "1932-6203", "PMID" : "18974833", "abstract" : "A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a \"cosmopolitan\" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.", "author" : [ { "dropping-particle" : "", "family" : "Keating", "given" : "Brendan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tischfield", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murray", "given" : "Sarah S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhangale", "given" : "Tushar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Thomas S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glessner", "given" : "Joseph T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galver", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrett", "given" : "Jeffrey C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "Struan F A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farlow", "given" : "Deborah N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandrupatla", "given" : "Hareesh R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ajmal", "given" : "Saad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papanicolaou", "given" : "George J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guo", "given" : "Yiran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Mingyao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Derohannessian", "given" : "Stephanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edmondson", "given" : "Andrew C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "Kent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gai", "given" : "Xiaowu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Susanna S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fornage", "given" : "Myriam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaikh", "given" : "Tamim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Alistair S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frackelton", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiang", "given" : "Charleston W K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Cecelia E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fabsitz", "given" : "Richard R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouwehand", "given" : "Willem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munroe", "given" : "Patricia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Drake", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whitehead", "given" : "A Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappola", "given" : "Thomas P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samani", "given" : "Nilesh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lusis", "given" : "A Jake", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schadt", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koenig", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabriel", "given" : "Stacey B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hakonarson", "given" : "Hakon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reilly", "given" : "Muredach", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nickerson", "given" : "Deborah A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fitzgerald", "given" : "Garret A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2008", "1", "31" ] ] }, "page" : "e3583", "publisher" : "Public Library of Science", "title" : "Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "163", "plainTextFormattedCitation" : "163", "previouslyFormattedCitation" : "163" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }163, as such it may not be equipped to appropriately address the question of substructure among South Asians. However, as the South Asians in this cohort were recruited mainly from one geographical region in South India, there likely is no substructure in this group. Conversely, the white Caucasians from EpiDREAM were recruited from several countries in Europe, North America, and Australia. While some previous literature investigating white Caucasian groups has shown evidence of a North-South gradientADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.0020143", "ISSN" : "1553-7404", "PMID" : "17044734", "abstract" : "Using a genome-wide single nucleotide polymorphism (SNP) panel, we observed population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests, there is a consistent and reproducible distinction between \"northern\" and \"southern\" European population groups: most individual participants with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the \"southern\" population; and most northern, western, eastern, and central Europeans have >90% in the \"northern\" population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the \"southern\" population, consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies.", "author" : [ { "dropping-particle" : "", "family" : "Seldin", "given" : "Michael F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shigeta", "given" : "Russell", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Villoslada", "given" : "Pablo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Selmi", "given" : "Carlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "Gabriel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belmont", "given" : "John W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klareskog", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregersen", "given" : "Peter K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2006", "9", "15" ] ] }, "page" : "e143", "publisher" : "Public Library of Science", "title" : "European population substructure: clustering of northern and southern populations.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "164", "plainTextFormattedCitation" : "164", "previouslyFormattedCitation" : "164" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }164, no substructure was found in our cohort. Secondly, we investigated inbreeding in both ethnicities. Our findings show no evidence of substantial inbreeding in either group, but indicate that South Asians were more inbred than Caucasians. This is congruent with previous researchADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nature08365", "ISSN" : "1476-4687", "PMID" : "19779445", "abstract" : "India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' (ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.", "author" : [ { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "7263", "issued" : { "date-parts" : [ [ "2009", "9", "24" ] ] }, "page" : "489-94", "title" : "Reconstructing Indian population history.", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ajhg.2013.07.006", "ISSN" : "1537-6605", "PMID" : "23932107", "abstract" : "Most Indian groups descend from a mixture of two genetically divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians (ASI) not closely related to groups outside the subcontinent. The date of mixture is unknown but has implications for understanding Indian history. We report genome-wide data from 73 groups from the Indian subcontinent and analyze linkage disequilibrium to estimate ANI-ASI mixture dates ranging from about 1,900 to 4,200 years ago. In a subset of groups, 100% of the mixture is consistent with having occurred during this period. These results show that India experienced a demographic transformation several thousand years ago, from a region in which major population mixture was common to one in which mixture even between closely related groups became rare because of a shift to endogamy.", "author" : [ { "dropping-particle" : "", "family" : "Moorjani", "given" : "Priya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lipson", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Po-Ru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Govindaraj", "given" : "Periyasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Bonnie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "9", "5" ] ] }, "page" : "422-38", "title" : "Genetic evidence for recent population mixture in India.", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "20,21", "plainTextFormattedCitation" : "20,21", "previouslyFormattedCitation" : "20,21" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20,21. The coefficient of inbreeding was calculated using pruned SNPs in linkage equilibrium and therefore approximately 20,000 SNPs were used in this estimation. As the procedure performs optimally in larger number of SNPs, preferably greater than 50,000, the estimate for the coefficient of inbreeding may be biasedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/519795", "ISSN" : "0002-9297", "PMID" : "17701901", "abstract" : "Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.", "author" : [ { "dropping-particle" : "", "family" : "Purcell", "given" : "Shaun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neale", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todd-Brown", "given" : "Kathe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Lori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Manuel A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bender", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maller", "given" : "Julian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sklar", "given" : "Pamela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "559-75", "title" : "PLINK: a tool set for whole-genome association and population-based linkage analyses.", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/s13742-015-0047-8", "ISSN" : "2047-217X", "PMID" : "25722852", "abstract" : "BACKGROUND: PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for faster and scalable implementations of key functions, such as logistic regression, linkage disequilibrium estimation, and genomic distance evaluation. In addition, GWAS and population-genetic data now frequently contain genotype likelihoods, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format.\n\nFINDINGS: To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, [Formula: see text]-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. We have also developed an extension to the data format which adds low-overhead support for genotype likelihoods, phase, multiallelic variants, and reference vs. alternate alleles, which is the basis of our planned second release (PLINK 2.0).\n\nCONCLUSIONS: The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.", "author" : [ { "dropping-particle" : "", "family" : "Chang", "given" : "Christopher C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chow", "given" : "Carson C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tellier", "given" : "Laurent CAM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vattikuti", "given" : "Shashaank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purcell", "given" : "Shaun M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "James J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "GigaScience", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "2", "25" ] ] }, "page" : "7", "title" : "Second-generation PLINK: rising to the challenge of larger and richer datasets", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "142,165", "plainTextFormattedCitation" : "142,165", "previouslyFormattedCitation" : "142,165" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }142,165.3.4.4 Strengths and limitationsThis study has several strengths. First, the sample was derived from a large multi-ethnic study and contained detailed assessment of dysglycemia and abdominal obesity. Additionally, evidence of genes associated with beta-cell impairment was systematically gathered in order to create a robust genotype score. Some limitations exist; first, as some genes implicated in pancreatic dysfunction were unavailable on the Illumina 50K IBC array, the genotype score was not exhaustive. Secondly, since EpiDREAM is a cohort of high-risk individuals, as determined by family history and abdominal obesity, the estimates ascertained from this analysis may not reflect the general population. Nevertheless, this should not affect our inter-ethnic comparisons as all individuals were recruited using the same criteria, and hence the results are internally valid. Lastly, our study used glucose testing to establish dysglycemia. Many institutions, including American Diabetes Association, the Endocrine Society, and the American Association of Clinical Endocrinologists/American College of Endocrinology, have endorsed the use of HbA1c in screening for and monitoring dysglycemiaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4158/EP.16.2.155", "ISSN" : "1934-2403", "PMID" : "20350901", "author" : [ { "dropping-particle" : "", "family" : "American Association of Clinical Endocrinologists", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "155-6", "title" : "American Association of Clinical Endocrinologists/American College of Endocrinology statement on the use of hemoglobin A1c for the diagnosis of diabetes.", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/dc09-9033", "ISSN" : "1935-5548", "PMID" : "19502545", "author" : [ { "dropping-particle" : "", "family" : "International Expert Committee", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2009", "7" ] ] }, "page" : "1327-34", "title" : "International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes.", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2337/dc10-S062", "ISSN" : "1935-5548", "PMID" : "20042775", "author" : [ { "dropping-particle" : "", "family" : "American Diabetes Association", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "S62-9", "title" : "Diagnosis and classification of diabetes mellitus.", "type" : "article-journal", "volume" : "33 Suppl 1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "166\u2013168", "plainTextFormattedCitation" : "166\u2013168", "previouslyFormattedCitation" : "166\u2013168" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }166–168. These recommendations were made based on overview of factors, such as inconvenience in acquiring fasting and OGTT measures, sample instability (i.e. glucose concentrations decrease in the test tube by 5–7% per hour due to glycolysisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc11-9998", "ISSN" : "1935-5548", "PMID" : "21617108", "abstract" : "BACKGROUND: Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially.\n\nAPPROACH: An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association.\n\nCONTENT: In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A(1c) (HbA(1c)) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of HbA(1c). The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed.\n\nSUMMARY: The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended.", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnold", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakris", "given" : "George L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruns", "given" : "David E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horvath", "given" : "Andrea Rita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirkman", "given" : "M Sue", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lernmark", "given" : "Ake", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metzger", "given" : "Boyd E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "e61-99", "title" : "Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "169", "plainTextFormattedCitation" : "169", "previouslyFormattedCitation" : "169" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }169), considerable intra-individual variation as a result of acute stressors (such as not finding parking prior to a visit), and nature of collection (including site of collection)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc10-1546", "ISSN" : "1935-5548", "PMID" : "21270207", "author" : [ { "dropping-particle" : "", "family" : "Sacks", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011", "2", "1" ] ] }, "page" : "518-23", "title" : "A1C versus glucose testing: a comparison.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "170", "plainTextFormattedCitation" : "170", "previouslyFormattedCitation" : "170" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }170. Use of HbA1c would overcome many of these limitations that can bias results and as such future investigations should seek to incorporate HbA1c as a measure of dysglycemia. However, researchers and reviewers should be cognizant of reported racial and ethnic differences in A1c concentrationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0149-5992", "PMID" : "9167108", "abstract" : "OBJECTIVE: To compare African-American and Caucasian patients with preexisting diabetes in a health maintenance organization (HMO) on: 1) frequency with which they received a subset of recommended laboratory tests according to the American Diabetes Association (ADA) consensus guidelines and 2) the results of laboratory test values (glycosylated hemoglobin, cholesterol, and creatinine).\n\nRESEARCH DESIGN AND METHODS: A cross-sectional study of 2,312 HMO members with diabetes continuously enrolled during 1991 was conducted using computerized medical record and billing data. Receipt of the ADA recommended tests for glycosylated hemoglobin, cholesterol, and creatinine was compared between African-Americans and Caucasians, stratified by insulin requirements. In addition, group comparisons were made based on the laboratory test results.\n\nRESULTS: Less than 20 percent of all subjects received the recommended number of ADA tests. This did not differ by race except for creatinine and cholesterol testing in insulin users only, where African-Americans had more tests. On average, after adjusting for covariates, African-Americans had significantly higher glycosylated hemoglobin and creatinine laboratory values. Both groups had elevated cholesterol values.\n\nCONCLUSIONS: The opportunity exists to improve the process of care for both African-Americans and Caucasians with diabetes in an HMO setting. The need to improve glycosylated hemoglobin results and subsequently limit complications is especially pressing among the African-American population.", "author" : [ { "dropping-particle" : "", "family" : "Wisdom", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fryzek", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Havstad", "given" : "S L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dreiling", "given" : "M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tilley", "given" : "B C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1997", "6" ] ] }, "page" : "971-7", "title" : "Comparison of laboratory test frequency and test results between African-Americans and Caucasians with diabetes: opportunity for improvement. Findings from a large urban health maintenance organization.", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Davidson", "given" : "MB", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schriger", "given" : "DL", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes Res Clin Pract.", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "415-421", "title" : "Effect of age and race/ethnicity on HbA1c levels in people without known diabetes mellitus: implications for the diagnosis of diabetes", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "171,172", "plainTextFormattedCitation" : "171,172", "previouslyFormattedCitation" : "171,172" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }171,172 when incorporating this measure in studies similar to ours.3.5 Conclusions A beta-cell impairment genotype score is associated with dysglycemia in South Asians and white Caucasians, although the per-allele effect appears to be greater in South Asians. The impact of genetic beta-cell impairment is magnified in South Asians with abdominal obesity.Chapter 4 Ethnic heterogeneity in DNA Methylation for birth weight and length 4.1 BackgroundDNA methylation is the reversible and heritable attachment of a methyl group to a nucleotide, commonly at the 5’ carbon of cytosine in dinucleotide consisting of cytosine and guanine (CpG). CpG sites are distributed throughout the genome; because methylcytosine spontaneously deaminates to thymine, there is a substantial underrepresentation of CpG sites in the genome, except in densely populated repeat elements / clusters and CpG islands (CGI)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/nar/gks928", "ISSN" : "1362-4962", "PMID" : "23066096", "abstract" : "Methylation of a CpG island is a faithful marker of silencing of its associated gene. Different approaches report the methylation status of a CpG island based on the determination of one or a few CpG sites by assuming the homogeneity of methylation along the element. This strategy is frequently applied in both locus-specific and genome-wide studies, but often without a validation of the representativeness of the interrogated CpG site compared with the whole element. We have evaluated the predictive informativeness of the HpaII sites located in CpG islands using data from high-resolution methylome maps, which offer the possibility to assess the methylation homogeneity of each CpG island and to determine the reporter accuracy of single sites as surrogate markers. An excellent correlation was observed between the HpaII and CpG island methylation levels (r > 0.93). At the qualitative level, the predictive sensitivity of HpaII was >95% with >92% specificity for methylated CpG islands and >90% sensitivity with >95% specificity for unmethylated CpG islands. This analysis provides a global validation framework for strategies based on the use of the methylation-sensitive HpaII restriction enzyme.", "author" : [ { "dropping-particle" : "", "family" : "Barrera", "given" : "V\u00edctor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peinado", "given" : "Miguel A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nucleic acids research", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2012", "12", "12" ] ] }, "page" : "11490-8", "title" : "Evaluation of single CpG sites as proxies of CpG island methylation states at the genome scale.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/bioinformatics/btt498", "ISSN" : "1367-4803", "PMID" : "23990415", "abstract" : "MOTIVATION: DNA methylation is a heritable modifiable chemical process that affects gene transcription and is associated with other molecular markers (e.g. gene expression) and biomarkers (e.g. cancer or other diseases). Current technology measures methylation in hundred of thousands, or millions of CpG sites throughout the genome. It is evident that neighboring CpG sites are often highly correlated with each other, and current literature suggests that clusters of adjacent CpG sites are co-regulated.\n\nRESULTS: We develop the Adjacent Site Clustering (A-clustering) algorithm to detect sets of neighboring CpG sites that are correlated with each other. To detect methylation regions associated with exposure, we propose an analysis pipeline for high-dimensional methylation data in which CpG sites within regions identified by A-clustering are modeled as multivariate responses to environmental exposure using a generalized estimating equation approach that assumes exposure equally affects all sites in the cluster. We develop a correlation preserving simulation scheme, and study the proposed methodology via simulations. We study the clusters detected by the algorithm on high dimensional dataset of peripheral blood methylation of pesticide applicators.\n\nAVAILABILITY: We provide the R package Aclust that efficiently implements the A-clustering and the analysis pipeline, and produces analysis reports. The package is found on \n\nCONTACT: tsofer@hsph.harvard.edu", "author" : [ { "dropping-particle" : "", "family" : "Sofer", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schifano", "given" : "E. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoppin", "given" : "J. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hou", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baccarelli", "given" : "A. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Bioinformatics", "id" : "ITEM-2", "issue" : "22", "issued" : { "date-parts" : [ [ "2013", "8", "29" ] ] }, "page" : "2884-2891", "title" : "A-clustering: a novel method for the detection of co-regulated methylation regions, and regions associated with exposure", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/nrg3273", "ISSN" : "1471-0064", "PMID" : "22986265", "abstract" : "DNA methylation is an epigenetic mark that has suspected regulatory roles in a broad range of biological processes and diseases. The technology is now available for studying DNA methylation genome-wide, at a high resolution and in a large number of samples. This Review discusses relevant concepts, computational methods and software tools for analysing and interpreting DNA methylation data. It focuses not only on the bioinformatic challenges of large epigenome-mapping projects and epigenome-wide association studies but also highlights software tools that make genome-wide DNA methylation mapping more accessible for laboratories with limited bioinformatics experience.", "author" : [ { "dropping-particle" : "", "family" : "Bock", "given" : "Christoph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Genetics", "id" : "ITEM-3", "issue" : "10", "issued" : { "date-parts" : [ [ "2012", "10" ] ] }, "page" : "705-19", "title" : "Analysing and interpreting DNA methylation data.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "173\u2013175", "plainTextFormattedCitation" : "173\u2013175", "previouslyFormattedCitation" : "173\u2013175" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }173–175. Considerable efforts have been made to identify these clusters; based on a relaxed correlation threshold 307,000 clusters were identified and 24,163 based on strict thresholdsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.febslet.2009.04.012", "ISSN" : "1873-3468", "PMID" : "19376112", "abstract" : "Mammalian genomes are punctuated by DNA sequences containing an atypically high frequency of CpG sites termed CpG islands (CGIs). CGIs generally lack DNA methylation and associate with the majority of annotated gene promoters. Many studies, however, have identified examples of CGI methylation in malignant cells, leading to improper gene silencing. CGI methylation also occurs in normal tissues and is known to function in X-inactivation and genomic imprinting. More recently, differential methylation has been shown between tissues, suggesting a potential role in transcriptional regulation during cell specification. Many of these tissue-specific methylated CGIs localise to regions distal to promoters, the regulatory function of which remains to be determined.", "author" : [ { "dropping-particle" : "", "family" : "Illingworth", "given" : "Robert S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bird", "given" : "Adrian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "FEBS letters", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2009", "6", "5" ] ] }, "page" : "1713-20", "title" : "CpG islands--'a rough guide'.", "type" : "article-journal", "volume" : "583" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "176", "plainTextFormattedCitation" : "176", "previouslyFormattedCitation" : "176" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }176. Most sites within clusters show a similar level of methylation and together may be involved in transcriptional regulation of genes and miRNAs, control of alternative promoter usage, and alternative splicing. Methylation in this manner is considered a mark of long-term inactivation of the associated geneADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/nar/gks928", "ISSN" : "1362-4962", "PMID" : "23066096", "abstract" : "Methylation of a CpG island is a faithful marker of silencing of its associated gene. Different approaches report the methylation status of a CpG island based on the determination of one or a few CpG sites by assuming the homogeneity of methylation along the element. This strategy is frequently applied in both locus-specific and genome-wide studies, but often without a validation of the representativeness of the interrogated CpG site compared with the whole element. We have evaluated the predictive informativeness of the HpaII sites located in CpG islands using data from high-resolution methylome maps, which offer the possibility to assess the methylation homogeneity of each CpG island and to determine the reporter accuracy of single sites as surrogate markers. An excellent correlation was observed between the HpaII and CpG island methylation levels (r > 0.93). At the qualitative level, the predictive sensitivity of HpaII was >95% with >92% specificity for methylated CpG islands and >90% sensitivity with >95% specificity for unmethylated CpG islands. This analysis provides a global validation framework for strategies based on the use of the methylation-sensitive HpaII restriction enzyme.", "author" : [ { "dropping-particle" : "", "family" : "Barrera", "given" : "V\u00edctor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peinado", "given" : "Miguel A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nucleic acids research", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2012", "12", "12" ] ] }, "page" : "11490-8", "title" : "Evaluation of single CpG sites as proxies of CpG island methylation states at the genome scale.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/bioinformatics/btt498", "ISSN" : "1367-4803", "PMID" : "23990415", "abstract" : "MOTIVATION: DNA methylation is a heritable modifiable chemical process that affects gene transcription and is associated with other molecular markers (e.g. gene expression) and biomarkers (e.g. cancer or other diseases). Current technology measures methylation in hundred of thousands, or millions of CpG sites throughout the genome. It is evident that neighboring CpG sites are often highly correlated with each other, and current literature suggests that clusters of adjacent CpG sites are co-regulated.\n\nRESULTS: We develop the Adjacent Site Clustering (A-clustering) algorithm to detect sets of neighboring CpG sites that are correlated with each other. To detect methylation regions associated with exposure, we propose an analysis pipeline for high-dimensional methylation data in which CpG sites within regions identified by A-clustering are modeled as multivariate responses to environmental exposure using a generalized estimating equation approach that assumes exposure equally affects all sites in the cluster. We develop a correlation preserving simulation scheme, and study the proposed methodology via simulations. We study the clusters detected by the algorithm on high dimensional dataset of peripheral blood methylation of pesticide applicators.\n\nAVAILABILITY: We provide the R package Aclust that efficiently implements the A-clustering and the analysis pipeline, and produces analysis reports. The package is found on \n\nCONTACT: tsofer@hsph.harvard.edu", "author" : [ { "dropping-particle" : "", "family" : "Sofer", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schifano", "given" : "E. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoppin", "given" : "J. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hou", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baccarelli", "given" : "A. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Bioinformatics", "id" : "ITEM-2", "issue" : "22", "issued" : { "date-parts" : [ [ "2013", "8", "29" ] ] }, "page" : "2884-2891", "title" : "A-clustering: a novel method for the detection of co-regulated methylation regions, and regions associated with exposure", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "173,174", "plainTextFormattedCitation" : "173,174", "previouslyFormattedCitation" : "173,174" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }173,174 and ultimately can impact how specific phenotypes or disease states develop.Considerable variation in body compositionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)15269-5", "ISSN" : "1474-547X", "PMID" : "14726172", "author" : [ { "dropping-particle" : "", "family" : "Yajnik", "given" : "Chittaranjan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yudkin", "given" : "John S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9403", "issued" : { "date-parts" : [ [ "2004", "1", "10" ] ] }, "language" : "English", "page" : "163", "publisher" : "Elsevier", "title" : "The Y-Y paradox.", "type" : "article-journal", "volume" : "363" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "10.1210/jcem.84.1.5371", "abstract" : "There is a high prevalence of type 2 diabetes mellitus and coronary artery disease among urban and migrant Asian Indians despite the absence of traditional risk factors. Evidence exists that Asian Indians are more hyperinsulinemic than Caucasians and that hyperinsulinemia may be important in the development of these diseases. To test whether insulin action was related to total or regional adiposity and to explore the potential role of plasma leptin and lipids, we measured insulin-mediated glucose disposal by the euglycemic insulin clamp, adipose distribution and muscle volume using computed axial tomography, and fasting serum leptin and lipid levels in 20 healthy Asian Indian male volunteers (age, 36 \u00b1 10 yr). A mean body mass index of 24.5 \u00b1 2.5 kg/m2 was associated with an unusually high percentage of body fat (33 \u00b1 7%). The majority of the fat was sc, and 16% was visceral (intraabdominal) adipose tissue. The majority (66%) of these nonobese men were insulin resistant. The mean fasting serum leptin leve...", "author" : [ { "dropping-particle" : "", "family" : "Banerji", "given" : "Mary Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faridi", "given" : "Nuzhat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atluri", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaiken", "given" : "Rochelle L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lebovitz", "given" : "Harold E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Clinical Endocrinology & Metabolism", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "7", "1" ] ] }, "language" : "en", "publisher" : "Endocrine Society", "title" : "Body Composition, Visceral Fat, Leptin, and Insulin Resistance in Asian Indian Men1", "type" : "article" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0000812", "ISSN" : "1932-6203", "author" : [ { "dropping-particle" : "", "family" : "Chandalia", "given" : "Manisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seenivasan", "given" : "Thanalakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Livingston", "given" : "Edward H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Snell", "given" : "Peter G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abate", "given" : "Nicola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS ONE", "editor" : [ { "dropping-particle" : "", "family" : "Maedler", "given" : "Kathrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8", "29" ] ] }, "page" : "e812", "title" : "Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1046/j.1467-789X.2002.00065.x", "ISSN" : "1467-7881", "author" : [ { "dropping-particle" : "", "family" : "Deurenberg", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deurenberg-Yap", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guricci", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity Reviews", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2002", "8" ] ] }, "page" : "141-146", "title" : "Asians are different from Caucasians and from each other in their body mass index/body fat per cent relationship", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "35\u201338", "plainTextFormattedCitation" : "35\u201338", "previouslyFormattedCitation" : "35\u201338" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }35–38 and adipose tissue distribution / storageADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2010.94", "ISSN" : "1930-739X", "PMID" : "20448537", "abstract" : "South Asians have a higher prevalence of cardiovascular disease (CVD) than Europeans. Studies have identified distinct subcompartments of subcutaneous adipose tissue (SAT) that provide insight into the relationship between abdominal obesity and metabolic risk factors in different ethnic groups. Our objective was to determine the relationship between SAT compartments and fat-free mass (FFM) between South Asian and European cohorts, and between men and women. Healthy Europeans and South Asians (n = 408) were assessed for FFM via dual energy X-ray absorptiometry, and SAT areas by computed tomography (CT). SAT was subdivided into superficial subcutaneous abdominal adipose tissue (SSAT) and deep subcutaneous abdominal adipose tissue (DSAT). Linear regression analyses were performed using DSAT and SSAT as separate dependent variables and FFM and ethnicity as primary independent variables adjusting for age, gender, income, education, and smoking status. Results showed that South Asian men had significantly higher amounts of DSAT (median 187.65 cm(2) vs. 145.15 cm(2), P < 0.001), SSAT (median 92.0 cm(2) vs. 76.1 cm(2), P = 0.046), and body fat mass (BFM) (25.1 kg vs. 22.6 kg, P = 0.049) than European men. In a fully adjusted model, South Asians showed significantly greater DSAT at any FFM than Europeans. Women had more SSAT at any given FFM than men and less DSAT at any given FFM than men, irrespective of ethnic background. In conclusion, South Asians had more DSAT than Europeans and men had relatively more DSAT than women. These data suggest that specific fat depots are influenced by ethnicity and gender; therefore, could provide insight into the relationship between ethnicity, gender and subsequent risk for CVD.", "author" : [ { "dropping-particle" : "", "family" : "Kohli", "given" : "Simi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sniderman", "given" : "Allan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tchernof", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lear", "given" : "Scott A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity (Silver Spring, Md.)", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "2177-83", "title" : "Ethnic-specific differences in abdominal subcutaneous adipose tissue compartments.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "40", "plainTextFormattedCitation" : "40", "previouslyFormattedCitation" : "40" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }40 exists between South Asians and white Caucasians, both at birthADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ije/dys139", "ISSN" : "1464-3685", "PMID" : "22984147", "abstract" : "BACKGROUND: South Asian children and adults have a more adipose body composition compared with those of European ancestry. This is thought to be related to their increased risk of metabolic disorders. However, little is known about how early in life such differences are manifest.\n\nOBJECTIVE: To determine whether there are differences in fat mass (FM) and fat-free mass (FFM) between UK-born South Asians and White Europeans in infancy. Design A cross-sectional study of 30 South Asian and 30 White European infants aged 6-12 weeks. Mothers were recruited from clinics in London, and infants' FM and FFM were determined using air-displacement plethysmography (PeaPod(\u00ae)).\n\nRESULTS: In early infancy South Asians had less FFM than White Europeans [0.34 kg less, 95% confidence interval (CI): 0.15, 0.52], with a considerably weaker indication of them also having more FM (0.02 kg more, 95% CI: -0.14, 0.18). These differences persisted when the overall smaller body size of South Asian infants was taken into account. For a given total infant weight, the balance of body composition of South Asians was shifted by 0.16 kg (95% CI: 0.06, 0.25) from FFM to FM. The ethnic differences in the amount of FFM were almost completely accounted for by ethnic differences in the rate of growth in utero and length of gestation.\n\nCONCLUSIONS: The characteristic differences in body composition observed between adult South Asians and White Europeans are apparent in early infancy. Of particular note is that this is the first study to demonstrate that South Asians compared with White Europeans have reduced FFM in infancy. The early manifestation of this phenotype suggests that it is either genetic and/or determined through exposure to maternal physiology, rather than a consequence of behaviours or diet in childhood or at older ages.", "author" : [ { "dropping-particle" : "", "family" : "Stanfield", "given" : "Kristina M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wells", "given" : "Jonathan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fewtrell", "given" : "Mary S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frost", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leon", "given" : "David A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "page" : "1409-18", "title" : "Differences in body composition between infants of South Asian and European ancestry: the London Mother and Baby Study.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1203/PDR.0b013e31819d98be", "ISSN" : "0031-3998", "abstract" : "Abdominal adiposity and metabolic ill health in Asian Indians are a growing public health concern. Causal pathways are unknown. Preventive measures in adults have had limited success. The aim of this observational case-control study was to compare adipose tissue partitioning in 69 healthy full term Asian Indian and white European newborns born in Pune, India and London, UK, respectively. The main outcome measures were total and regional adipose tissue content measured by whole body magnetic resonance imaging. Although smaller in weight (95% CI for difference \u22120.757 to \u22120.385 kg, p < 0.001), head circumference (\u22122.15 to \u22120.9 cm, p < 0.001), and length (\u22122.9 to \u22121.1 cm p < 0.001), the Asian Indian neonates had significantly greater absolute adiposity in all three abdominal compartments, internal (visceral) (0.012\u20130.023 L, p < 0.001), deep s.c. (0.003\u20130.017 L, p = 0.006) and superficial s.c. (0.006\u20130.043 L, p = 0.011) and a significant reduction in nonabdominal superficial s.c. adipose tissue (\u22120.184 to \u22120.029 L, p = 0.008) in comparison to the white European babies despite similar whole body adipose tissue content (\u22120.175 to 0.034 L, p = 0.2). We conclude that differences in adipose tissue partitioning exist at birth. Investigative, screening, and preventive measures must involve maternal health, intrauterine life, and infancy.", "author" : [ { "dropping-particle" : "", "family" : "Modi", "given" : "Neena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "E Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uthaya", "given" : "Sabita N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Umranikar", "given" : "Shalini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "Jimmy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "Chittaranjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatric Research", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5" ] ] }, "page" : "584-587", "publisher" : "International Pediatrics Research Foundation, Inc.", "title" : "Whole Body Magnetic Resonance Imaging of Healthy Newborn Infants Demonstrates Increased Central Adiposity in Asian Indians", "title-short" : "Pediatr Res", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1210/jc.2002-020434", "ISSN" : "0021-972X", "abstract" : "We studied body size and cord blood leptin and insulin concentrations in newborn urban Indian (Pune, India) and white Caucasian (London, UK) babies to test the hypothesis that the adiposity and hyperinsulinemia of Indians are present at birth. Indian babies (n = 157) were lighter in weight compared with white Caucasian babies [n = 67; median weight, 2805 g vs. 3475 g, respectively; P < 0.001, adjusted for gestational age and sex; \u22121.52 sd score; confidence interval (CI), \u22121.66, \u22121.42] and had smaller abdominal (\u22122.39 sd score; CI, \u22122.52, \u22122.09), midarm (\u22121.47 sd score; CI, \u22121.58, \u22121.34), and head (\u22121.23 sd score; CI, \u22121.42, \u22121.13) circumferences. However, their skinfolds were relatively preserved: subscapular (central) skinfold (\u22120.32 sd score; CI, \u22120.43, \u22120.20) was better preserved than triceps (peripheral) skinfold (\u22120.86 sd score; CI, \u22120.97, \u22120.75). Cord plasma leptin (median, 6.2 ng/ml Pune and 6.4 ng/ml London) and insulin (median, 34.7 pmol/liter Pune and 20.8 pmol/liter London) concentrations were ...", "author" : [ { "dropping-particle" : "", "family" : "Yajnik", "given" : "C. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lubree", "given" : "H. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rege", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naik", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshpande", "given" : "J. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshpande", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V.", "family" : "Joglekar", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yudkin", "given" : "J. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Clinical Endocrinology & Metabolism", "id" : "ITEM-3", "issue" : "12", "issued" : { "date-parts" : [ [ "2002", "12", "2" ] ] }, "language" : "en", "page" : "5575-5580", "publisher" : "Endocrine Society", "title" : "Adiposity and Hyperinsulinemia in Indians Are Present at Birth", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1093/ije/dyq180", "ISSN" : "1464-3685", "PMID" : "21044977", "abstract" : "BACKGROUND: The objective of this study was to examine adiposity patterns in UK South Asian, black African-Caribbean and white European children using a range of adiposity markers. A cross-sectional survey in London, Birmingham and Leicester primary schools was conducted. Weight, height, waist circumference, skinfold thickness values (biceps, triceps, subscapular and suprailiac) were measured. Fat mass was derived from bioimpedance; optimally height-standardized indices were derived for all adiposity markers. Ethnic origin was based on parental self-report. Multilevel models were used to obtain adjusted means and ethnic differences adjusted for gender, age, month, observer and school (fitted as a random effect). A total of 5887 children aged 9-10 years participated (response rate 68%), including 1345 white Europeans, 1523 South Asians and 1570 black African-Caribbeans.\n\nRESULTS: Compared with white Europeans, South Asians had a higher sum of all skinfolds and fat mass percentage, and their body mass index (BMI) was lower. South Asians were slightly shorter but use of optimally height-standardized indices did not materially affect these comparisons. At any given fat mass, BMI was lower in South Asians than white Europeans. In similar comparisons, black African-Caribbeans had a lower sum of all skinfolds but a higher fat mass percentage, and their BMI was higher. Black African-Caribbeans were markedly taller. Use of optimally height-standardized indices yielded markedly different findings; sum of skinfolds index was markedly lower, whereas fat mass index and weight-for-height index were similar. At any given fat mass, BMI was similar in black African-Caribbeans and white Europeans.\n\nCONCLUSIONS: UK South Asian children have higher adiposity levels and black African-Caribbeans have similar or lower adiposity levels when compared with white Europeans. However, these differences are not well represented by comparisons based on BMI, which systematically underestimates adiposity in South Asians, and in black African-Caribbeans it overestimates adiposity because of its association with height.", "author" : [ { "dropping-particle" : "", "family" : "Nightingale", "given" : "Claire M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudnicka", "given" : "Alicja R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Chris G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "Derek G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whincup", "given" : "Peter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "2", "1" ] ] }, "page" : "33-44", "title" : "Patterns of body size and adiposity among UK children of South Asian, black African-Caribbean and white European origin: Child Heart And health Study in England (CHASE Study).", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "53\u201356", "plainTextFormattedCitation" : "53\u201356", "previouslyFormattedCitation" : "53\u201356" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }53–56 and as adults. These differences contribute to cardiometabolic traits such as dyslipidemia and dysglycemiaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ije/dyl245", "ISSN" : "0300-5771", "PMID" : "17510078", "abstract" : "The rates of coronary disease have accelerated dramatically amongst South Asians, driven to an important extent by the atherogenic dyslipidemia and type 2 diabetes that have become so common amongst them. These precursors of vascular disease appear at lower absolute amounts of adipose tissue in South Asians than in whites. In this paper, we set out a new hypothesis--the adipose tissue overflow hypothesis--to account for these findings. The adipose tissue mass within our bodies can be divided into three different compartments: superficial subcutaneous adipose tissue, deep subcutaneous adipose tissue and visceral adipose tissue. The superficial subcutaneous adipose tissue compartment is the primary compartment, is present throughout the body, and constitutes the vast majority of the adipose tissue in the lower limb. With energy excess, the secondary adipose tissue compartments--the deep subcutaneous (mainly upper body) and the visceral adipose tissue compartments--become more prominent. Superficial subcutaneous adipose tissue is relatively inert metabolically, whereas the other two compartments are characterized by higher transmembrane fatty acid flux rates and thus are more closely linked to dyslipidemia and dysglycemia. We hypothesize that the superficial subcutaneous adipose tissue compartment is larger in whites than in South Asians. If so, as obesity develops, South Asians exhaust the storage capacity of their superficial subcutaneous adipose tissue compartment before whites do and that is why they develop the metabolic complications of upper body obesity at lower absolute masses of adipose tissue than white people.", "author" : [ { "dropping-particle" : "", "family" : "Sniderman", "given" : "Allan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhopal", "given" : "Raj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarrafzadegan", "given" : "Nizal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tchernof", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "2", "1" ] ] }, "page" : "220-5", "title" : "Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "33", "plainTextFormattedCitation" : "33", "previouslyFormattedCitation" : "33" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }33. As differences in body composition are present at birth, the variation is likely a result of altered genetic predisposition and/or the in-utero environment, or their interactions. Since both genetic and environmental factors can independently and together alter methylation of genes, having downstream effects on the expression of genes, it is an intriguing field of study to explain the ethnic heterogeneity between South Asians and white Caucasians. Despite a strong rationale to explain ethnic heterogeneity, very few studies have explored whether DNA methylation is associated with differences in birth weight and length between ethnic groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s13148-015-0080-6", "ISSN" : "1868-7075", "abstract" : "The birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities. The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race and birth weight. Data was collected on a cohort of 87 live born infants. IGF1 methylation was measured in DNA isolated from the mononuclear fraction of umbilical cord blood collected after delivery. Quantitative, loci-specific methylation was assessed using the Infinium HumanMethylation27 BeadArray (Illumina Inc., San Diego, CA). Locus specific methylation of the IGF1 CpG site was validated on a subset of the original sample (N\u2009=\u200961) using pyrosequencing. Multiple linear regression was used to examine relationships between IGF1 methylation, race, and birth weight. A formal mediation analysis was then used to estimate the relationship of IGF1 methylation to race and birth weight.", "author" : [ { "dropping-particle" : "", "family" : "Straughen", "given" : "Jennifer K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sipahi", "given" : "Levent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uddin", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Misra", "given" : "Dawn P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Misra", "given" : "Vinod K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Epigenetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "4", "21" ] ] }, "language" : "en", "page" : "47", "publisher" : "BioMed Central Ltd", "title" : "Racial differences in IGF1 methylation and birth weight", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/jech-2014-204781", "ISSN" : "1470-2738", "PMID" : "25678712", "abstract" : "BACKGROUND: Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood.\n\nMETHODS: We measured DNA methylation at DMRs regulating genomically imprinted domains (IGF2/H19, DLK1/MEG3, NNAT and PLAGL1) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010-2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences.\n\nRESULTS: Unadjusted race/ethnic differences only were evident for DMRs regulating MEG3 and IGF2; race/ethnic differences persisted in IGF2/H19 and NNAT after accounting for income and education.\n\nCONCLUSIONS: Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers.", "author" : [ { "dropping-particle" : "", "family" : "King", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murphy", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoyo", "given" : "Cathrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of epidemiology and community health", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015", "2", "12" ] ] }, "title" : "Epigenetic regulation of Newborns' imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "177,178", "plainTextFormattedCitation" : "177,178", "previouslyFormattedCitation" : "177,178" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }177,178. Furthermore, of the work published, both GWA-ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2477", "ISSN" : "1546-1718", "PMID" : "23202124", "abstract" : "Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.", "author" : [ { "dropping-particle" : "", "family" : "Horikoshi", "given" : "Momoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yaghootkar", "given" : "Hanieh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mook-Kanamori", "given" : "Dennis O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taal", "given" : "H Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hennig", "given" : "Branwen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bradfield", "given" : "Jonathan P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "St Pourcain", "given" : "Beate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charoen", "given" : "Pimphen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cousminer", "given" : "Diana L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtim\u00e4ki", "given" : "Terho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kreiner-M\u00f8ller", "given" : "Eskil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warrington", "given" : "Nicole M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bustamante", "given" : "Mariona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feenstra", "given" : "Bjarke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berry", "given" : "Diane J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thiering", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfab", "given" : "Thiemo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barton", "given" : "Sheila J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kerkhof", "given" : "Marjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leeuwen", "given" : "Elisabeth M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulford", "given" : "Anthony J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kutalik", "given" : "Zolt\u00e1n", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindi", "given" : "Virpi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goh", "given" : "Liang-Kee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raitakari", "given" : "Olli T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harder", "given" : "Marie N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meirhaeghe", "given" : "Aline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ntalla", "given" : "Ioanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salem", "given" : "Rany M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jameson", "given" : "Karen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhou", "given" : "Kaixin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monies", "given" : "Dorota M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirin", "given" : "Mirna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heikkinen", "given" : "Jani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adair", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alkuraya", "given" : "Fowzan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Odaib", "given" : "Ali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amouyel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersson", "given" : "Ehm Astrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blakemore", "given" : "Alexandra I F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buxton", "given" : "Jessica L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dallongeville", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Shikta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estivill", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flexeder", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geller", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godfrey", "given" : "Keith M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gottrand", "given" : "Fr\u00e9d\u00e9ric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Hollegaard", "given" : "Mads", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hougaard", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hypp\u00f6nen", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Inskip", "given" : "Hazel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isaacs", "given" : "Aaron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanaka-Gantenbein", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemp", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiess", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kilpel\u00e4inen", "given" : "Tuomas O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Bridget A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuzawa", "given" : "Christopher W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McMahon", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Newnham", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niinikoski", "given" : "Harri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Postma", "given" : "Dirkje S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "Susan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sebert", "given" : "Sylvain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simell", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slowinski", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiesler", "given" : "Carla M T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaag", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viikari", "given" : "Jorma S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vink", "given" : "Jacqueline M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vissing", "given" : "Nadja Hawwa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witte", "given" : "Daniel R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Haitao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jianhua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prentice", "given" : "Andrew M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Brian F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Ewan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boreham", "given" : "Colin A G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillman", "given" : "Matthew W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreno", "given" : "Luis A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saarinen", "given" : "Maiju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saw", "given" : "Seang-Mei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6rner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Ken K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koppelman", "given" : "Gerard H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holloway", "given" : "John W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hocher", "given" : "Berthold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heinrich", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Power", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melbye", "given" : "Mads", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guxens", "given" : "M\u00f2nica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennell", "given" : "Craig E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f8nnelykke", "given" : "Klaus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bisgaard", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wid\u00e9n", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hakonarson", "given" : "Hakon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "Struan F A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Jaddoe", "given" : "Vincent W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "76-82", "title" : "New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1086/518517", "ISSN" : "0002-9297", "PMID" : "17503332", "abstract" : "The role of genes in normal birth-weight variation is poorly understood, and it has been suggested that the genetic component of fetal growth is small. Type 2 diabetes genes may influence birth weight through maternal genotype, by increasing maternal glycemia in pregnancy, or through fetal genotype, by altering fetal insulin secretion. We aimed to assess the role of the recently described type 2 diabetes gene TCF7L2 in birth weight. We genotyped the polymorphism rs7903146 in 15,709 individuals whose birth weight was available from six studies and in 8,344 mothers from three studies. Each fetal copy of the predisposing allele was associated with an 18-g (95% confidence interval [CI] 7-29 g) increase in birth weight (P=.001) and each maternal copy with a 30-g (95% CI 15-45 g) increase in offspring birth weight (P=2.8x10-5). Stratification by fetal genotype suggested that the association was driven by maternal genotype (31-g [95% CI 9-48 g] increase per allele; corrected P=.003). Analysis of diabetes-related traits in 10,314 nondiabetic individuals suggested the most likely mechanism is that the risk allele reduces maternal insulin secretion (disposition index reduced by ~0.15 standard deviation; P=1x10-4), which results in increased maternal glycemia in pregnancy and hence increased offspring birth weight. We combined information with the other common variant known to alter fetal growth, the -30G-->A polymorphism of glucokinase (rs1799884). The 4% of offspring born to mothers carrying three or four risk alleles were 119 g (95% CI 62-172 g) heavier than were the 32% born to mothers with none (for overall trend, P=2x10-7), comparable to the impact of maternal smoking during pregnancy. In conclusion, we have identified the first type 2 diabetes-susceptibility allele to be reproducibly associated with birth weight. Common gene variants can substantially influence normal birth-weight variation.", "author" : [ { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hypponen", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Relton", "given" : "Caroline L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parnell", "given" : "Kirstie S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "Susan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pembrey", "given" : "Marcus E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strachan", "given" : "David P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Power", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davey Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2007", "6", "6" ] ] }, "language" : "English", "page" : "1150-61", "publisher" : "Elsevier", "title" : "Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2337/db08-1739", "ISSN" : "1939-327X", "PMID" : "19228808", "abstract" : "OBJECTIVE: Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight.\n\nRESEARCH DESIGN AND METHODS: We genotyped single-nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four studies of white Europeans. We tested the association between maternal or fetal genotype at each locus and birth weight of the offspring.\n\nRESULTS: We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with reduced birth weight when inherited by the fetus (21 g [95% CI 11-31], P = 2 x 10(-5), and 14 g [4-23], P = 0.004, lower birth weight per risk allele, respectively). The 4% of offspring carrying four risk alleles at these two loci were 80 g (95% CI 39-120) lighter at birth than the 8% carrying none (P(trend) = 5 x 10(-7)). There were no associations between birth weight and fetal genotypes at the three other loci or maternal genotypes at any locus.\n\nCONCLUSIONS: Our results are in keeping with the fetal insulin hypothesis and provide robust evidence that common disease-associated variants can alter size at birth directly through the fetal genotype.", "author" : [ { "dropping-particle" : "", "family" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "Susan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hypp\u00f6nen", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Power", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strachan", "given" : "David P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00e4rvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2009", "6", "1" ] ] }, "page" : "1428-33", "title" : "Type 2 diabetes risk alleles are associated with reduced size at birth.", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "179\u2013181", "plainTextFormattedCitation" : "179\u2013181", "previouslyFormattedCitation" : "179\u2013181" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }179–181 and methylation studiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/aje/kwt433", "ISSN" : "1476-6256", "PMID" : "24561991", "abstract" : "Although epigenetic regulation plays a critical role in embryonic development, few studies have examined the relationship of epigenome-wide methylation with fetal growth. Using the Infinium HumanMethylation450 BeadChip (Illumina, Inc., San Diego, California) in a substudy of 1,046 infants from the Norwegian Mother and Child Cohort Study (MoBa) enrolled between 1999 and 2008, we examined epigenome-wide cord blood DNA methylation in relation to birth weight. In multivariable-adjusted robust linear regression models, we identified differential methylation at 19 cytosine-guanine dinucleotides (CpGs) associated with either decreased (AT-rich interactive domain 5B (MRF1-like) (ARID5B), 2 CpGs) or increased (x-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3), 4 CpGs) birth weight. ARID5B knockout mice have less adipose tissue and significantly lower weight in the postnatal period. XRCC3 plays a key role in the maintenance of chromosome stability and the repair of DNA damage. Although there are fewer data on the other implicated genes, many of these genes have been shown to have roles in developmental processes. This constitutes the largest and most robust study of birth weight using an epigenome-wide methylation platform and offers potential insights into epigenetic mechanisms of fetal growth.", "author" : [ { "dropping-particle" : "", "family" : "Engel", "given" : "Stephanie M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joubert", "given" : "Bonnie R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Michael C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olshan", "given" : "Andrew F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e5berg", "given" : "Siri E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ueland", "given" : "Per Magne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nystad", "given" : "Wenche", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsen", "given" : "Roy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollset", "given" : "Stein Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peddada", "given" : "Shyamal D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "London", "given" : "Stephanie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of epidemiology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2014", "4", "1" ] ] }, "page" : "834-42", "title" : "Neonatal genome-wide methylation patterns in relation to birth weight in the Norwegian Mother and Child Cohort.", "type" : "article-journal", "volume" : "179" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1186/1755-8794-5-10", "ISSN" : "1755-8794", "PMID" : "22498030", "abstract" : "BACKGROUND: Infant birth weight is a complex quantitative trait associated with both neonatal and long-term health outcomes. Numerous studies have been published in which candidate genes (IGF1, IGF2, IGF2R, IGF binding proteins, PHLDA2 and PLAGL1) have been associated with birth weight, but these studies are difficult to reproduce in man and large cohort studies are needed due to the large inter individual variance in transcription levels. Also, very little of the trait variance is explained. We decided to identify additional candidates without regard for what is known about the genes. We hypothesize that DNA methylation differences between individuals can serve as markers of gene \"expression potential\" at growth related genes throughout development and that these differences may correlate with birth weight better than single time point measures of gene expression.\n\nMETHODS: We performed DNA methylation and transcript profiling on cord blood and placenta from newborns. We then used novel computational approaches to identify genes correlated with birth weight.\n\nRESULTS: We identified 23 genes whose methylation levels explain 70-87% of the variance in birth weight. Six of these (ANGPT4, APOE, CDK2, GRB10, OSBPL5 and REG1B) are associated with growth phenotypes in human or mouse models. Gene expression profiling explained a much smaller fraction of variance in birth weight than did DNA methylation. We further show that two genes, the transcriptional repressor MSX1 and the growth factor receptor adaptor protein GRB10, are correlated with transcriptional control of at least seven genes reported to be involved in fetal or placental growth, suggesting that we have identified important networks in growth control. GRB10 methylation is also correlated with genes involved in reactive oxygen species signaling, stress signaling and oxygen sensing and more recent data implicate GRB10 in insulin signaling.\n\nCONCLUSIONS: Single time point measurements of gene expression may reflect many factors unrelated to birth weight, while inter-individual differences in DNA methylation may represent a \"molecular fossil record\" of differences in birth weight-related gene expression. Finding these \"unexpected\" pathways may tell us something about the long-term association between low birth weight and adult disease, as well as which genes may be susceptible to environmental effects. These findings increase our understanding of the molecular mechanisms involved in human development an\u2026", "author" : [ { "dropping-particle" : "", "family" : "Turan", "given" : "Nahid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghalwash", "given" : "Mohamed F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katari", "given" : "Sunita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coutifaris", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Obradovic", "given" : "Zoran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sapienza", "given" : "Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genomics", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "10", "title" : "DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease?", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "182,183", "plainTextFormattedCitation" : "182,183", "previouslyFormattedCitation" : "182,183" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }182,183 are predominantly performed in white Caucasians. No genome-wide search of SNPs or CpG sites for birth weight has been undertaken in South Asians alone or comparing South Asians and white Caucasians. Since methylation can be important in identifying the phenotypic differences, we investigated whether ethnic heterogeneity between South Asians and white Caucasians exists in the effect of methylation on birth weight and length. The purpose of this chapter was to: (1) explore ethnic heterogeneity in methylation at known birth weight and length genes; (2) conduct a regional analysis to assess the relationship of the entire CpG cluster with the birth weight / length in genes that were significant from our primary analysis; and (3) perform a genome-wide search of CpG sites related to birth weight in South Asians.4.2 Methods4.2.1 ParticipantsData for 250 unrelated South Asian newborns from the South Asian Birth Cohort (START) and 274 unrelated white Caucasian newborns from the Canadian Healthy Infant Longitudinal Development (CHILD) study were acquired. Individuals were considered South Asian if both parents originated from the Indian subcontinent. Newborns were white Caucasian if both parents were whites of European origin. Details of these cohorts have been reported previouslyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2458-13-79", "ISSN" : "1471-2458", "PMID" : "23356884", "abstract" : "BACKGROUND: People who originate from the Indian subcontinent (South Asians) suffer among the highest rates of type 2 diabetes in the world. Prior evidence suggests that metabolic risk factors develop early in life and are influenced by maternal and paternal behaviors, the intrauterine environment, and genetic factors. The South Asian Birth Cohort Study (START) will investigate the environmental and genetic basis of adiposity among 750 South Asian offspring recruited from highly divergent environments, namely, rural and urban India and urban Canada.\n\nMETHODS: Detailed information on health behaviors including diet and physical activity, and blood samples for metabolic parameters and DNA are collected from pregnant women of South Asian ancestry who are free of significant chronic disease. They also undergo a provocative test to diagnose impaired glucose tolerance and gestational diabetes. At delivery, cord blood and newborn anthropometric indices (i.e. birth weight, length, head circumference and skin fold thickness) are collected. The mother and growing offspring are followed prospectively and information on the growth trajectory, adiposity and health behaviors will be collected annually up to age 3 years. Our aim is to recruit a minimum of 750 mother-infant pairs equally divided between three divergent environments: rural India, urban India, and Canada.\n\nSUMMARY: The START cohort will increase our understanding of the environmental and genetic determinants of adiposity and related metabolic abnormalities among South Asians living in India and Canada.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vasudevan", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Milan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurpad", "given" : "Anura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Koon K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinivasan", "given" : "Krishnamachari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC public health", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "79", "title" : "Rationale and design of South Asian Birth Cohort (START): a Canada-India collaborative study.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/jes.2015.7", "ISSN" : "1559-064X", "PMID" : "25805254", "abstract" : "The Canadian Healthy Infant Longitudinal Development birth cohort was designed to elucidate interactions between environment and genetics underlying development of asthma and allergy. Over 3600 pregnant mothers were recruited from the general population in four provinces with diverse environments. The child is followed to age 5 years, with prospective characterization of diverse exposures during this critical period. Key exposure domains include indoor and outdoor air pollutants, inhalation, ingestion and dermal uptake of chemicals, mold, dampness, biological allergens, pets and pests, housing structure, and living behavior, together with infections, nutrition, psychosocial environment, and medications. Assessments of early life exposures are focused on those linked to inflammatory responses driven by the acquired and innate immune systems. Mothers complete extensive environmental questionnaires including time-activity behavior at recruitment and when the child is 3, 6, 12, 24, 30, 36, 48, and 60 months old. House dust collected during a thorough home assessment at 3-4 months, and biological specimens obtained for multiple exposure-related measurements, are archived for analyses. Geo-locations of homes and daycares and land-use regression for estimating traffic-related air pollution complement time-activity-behavior data to provide comprehensive individual exposure profiles. Several analytical frameworks are proposed to address the many interacting exposure variables and potential issues of co-linearity in this complex data set.Journal of Exposure Science and Environmental Epidemiology advance online publication, 25 March 2015; doi:10.1038/jes.2015.7.", "author" : [ { "dropping-particle" : "", "family" : "Takaro", "given" : "Tim K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allen", "given" : "Ryan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Allan B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Befus", "given" : "A Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brauer", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "Joanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lefebvre", "given" : "Diana L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lou", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandhane", "given" : "Piush J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McLean", "given" : "Kathleen E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Gregory", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sbihi", "given" : "Hind", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shu", "given" : "Huan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subbarao", "given" : "Padmaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turvey", "given" : "Stuart E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeng", "given" : "Leilei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sears", "given" : "Malcolm R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brook", "given" : "Jeffrey R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of exposure science & environmental epidemiology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2015", "3", "25" ] ] }, "title" : "The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: assessment of environmental exposures.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "63,184", "plainTextFormattedCitation" : "63,184", "previouslyFormattedCitation" : "63,184" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }63,184 and the specific inclusion and exclusion criteria are presented in Supplementary Table 4.1. Briefly, the START and CHILD cohorts recruited pregnant mothers above the age of 18 during the first or second trimester; the pregnant women, along with their newborns, are prospectively followed for 3 to 5 years. Anthropometric measurements and cord blood are collected for the mother-baby pairs at birth and at each subsequent visit. Informed consent was obtained from all participants. Ethics boards at Hamilton Health Sciences, Trillium Health Partners, and the William Osler Health System approved the START study and ethics boards at St. Joseph’s Healthcare, University of Alberta, Covenant Health, Alberta Health Services, BC Children’s hospital, University of Manitoba, Health Science Centre Winnipeg, St. Boniface General Hospital, Regional Health Authority – Central Manitoba Inc., Manitoba Health Information Privacy Committee, University of British Columbia, Children’s and Women’s Hospital, St. Paul’s Hospital – Providence Health Care, Simon Fraser University, and Vancouver Coastal Health Research Institute approved the CHILD study.4.2.3 Quality control proceduresThe following quality control procedures were undertaken prior to conducting the main analysis. Methods describing our main analysis follow (Sections 4.2.4 – 4.2.6).Methylation probe site quality control: DNA was extracted from cord blood. Data on methylation of DNA were available for 274 CHILD and 250 START participants. Quality control assessments were conducted in R using the ChAMP and minfi bioconductor packages. Raw intensity signals (*.idat files) were imported from the Infinium Illumina HumanMethylation450 BeadChip. Singular Value Decomposition (SVD) analysis was performed to identify technical variation between the samples (i.e., array, slide, or batch effect). The analysis demonstrated that the primary sources of variation within and between samples were not technical. The following exclusions were made for CpG probe sites: probes on the X- or Y-chromosomes and any probe with a detection p-value of ≤ 0.05ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(13)62674-4", "ISSN" : "1474-547X", "PMID" : "24630777", "abstract" : "BACKGROUND: Obesity is a major health problem that is determined by interactions between lifestyle and environmental and genetic factors. Although associations between several genetic variants and body-mass index (BMI) have been identified, little is known about epigenetic changes related to BMI. We undertook a genome-wide analysis of methylation at CpG sites in relation to BMI.\n\nMETHODS: 479 individuals of European origin recruited by the Cardiogenics Consortium formed our discovery cohort. We typed their whole-blood DNA with the Infinium HumanMethylation450 array. After quality control, methylation levels were tested for association with BMI. Methylation sites showing an association with BMI at a false discovery rate q value of 0\u00b705 or less were taken forward for replication in a cohort of 339 unrelated white patients of northern European origin from the MARTHA cohort. Sites that remained significant in this primary replication cohort were tested in a second replication cohort of 1789 white patients of European origin from the KORA cohort. We examined whether methylation levels at identified sites also showed an association with BMI in DNA from adipose tissue (n=635) and skin (n=395) obtained from white female individuals participating in the MuTHER study. Finally, we examined the association of methylation at BMI-associated sites with genetic variants and with gene expression.\n\nFINDINGS: 20 individuals from the discovery cohort were excluded from analyses after quality-control checks, leaving 459 participants. After adjustment for covariates, we identified an association (q value \u22640\u00b705) between methylation at five probes across three different genes and BMI. The associations with three of these probes--cg22891070, cg27146050, and cg16672562, all of which are in intron 1 of HIF3A--were confirmed in both the primary and second replication cohorts. For every 0\u00b71 increase in methylation \u03b2 value at cg22891070, BMI was 3\u00b76% (95% CI 2\u00b74-4\u00b79) higher in the discovery cohort, 2\u00b77% (1\u00b72-4\u00b72) higher in the primary replication cohort, and 0\u00b78% (0\u00b72-1\u00b74) higher in the second replication cohort. For the MuTHER cohort, methylation at cg22891070 was associated with BMI in adipose tissue (p=1\u00b772\u2008\u00d7\u200810(-5)) but not in skin (p=0\u00b7882). We observed a significant inverse correlation (p=0\u00b7005) between methylation at cg22891070 and expression of one HIF3A gene-expression probe in adipose tissue. Two single nucleotide polymorphisms--rs8102595 and rs3826795--had independent ass\u2026", "author" : [ { "dropping-particle" : "", "family" : "Dick", "given" : "Katherine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nelson", "given" : "Christopher P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsaprouni", "given" : "Loukia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandling", "given" : "Johanna K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "A\u00efssi", "given" : "Dylan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahl", "given" : "Simone", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meduri", "given" : "Eshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morange", "given" : "Pierre-Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gagnon", "given" : "France", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waldenberger", "given" : "Melanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdmann", "given" : "Jeanette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hengstenberg", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cambien", "given" : "Francois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodall", "given" : "Alison H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouwehand", "given" : "Willem H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schunkert", "given" : "Heribert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Tim D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tr\u00e9gou\u00ebt", "given" : "David-Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samani", "given" : "Nilesh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9933", "issued" : { "date-parts" : [ [ "2014", "6", "7" ] ] }, "page" : "1990-8", "title" : "DNA methylation and body-mass index: a genome-wide analysis.", "type" : "article-journal", "volume" : "383" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "185", "plainTextFormattedCitation" : "185", "previouslyFormattedCitation" : "185" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }185. Based on these criteria, 8,634 (1.82%) and 12,598 (2.66%) of 474,209 probes were removed from the START and CHILD cohorts, respectively, leaving 465,575 probes in START and 461,611 probes in CHILD available for analysis. The following exclusions were made at the participant-level: individuals with discordant methylation-identified and reported phenotypic sex and those with ≥ 0.01 missing probes. Nine samples from START and 16 from CHILD demonstrated discordant sex, and 1 sample from START and 9 samples from CHILD failed probe detection. These samples were removed from the analysis. After quality control, 234 South Asian and 250 white Caucasian newborns were available for methylation analysis. Finally, to correct for differences in distribution and intensity between the Infinium type-I and type-II methylation probes used by the HumanMethylation450k platform, Subset-quantile Within Array Normalization (SWAN) was performed.Genotyping quality control: Genetic data from newborns were available for 244 START participants and 204 CHILD participants. Genotyping was performed using the Illumina Human Core Exome 12 (version 1.1). Standard assessments were conducted to ensure quality of genotyping. SNPs chosen for the main analysis (see Section 4.2.4 below) were in agreement with Hardy Weinberg Equilibrium (P>1.00x10-3), had a minor allele frequency ≥ 5%, and displayed call rates greater than 95% (Supplementary Table 4.2). Presence of inbreeding was assessed using SNPs in approximate linkage equilibrium, automatically selected from genome-wide data (542,585 markers) using LD-based pruning in PLINKADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/519795", "ISSN" : "0002-9297", "PMID" : "17701901", "abstract" : "Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.", "author" : [ { "dropping-particle" : "", "family" : "Purcell", "given" : "Shaun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neale", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todd-Brown", "given" : "Kathe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Lori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Manuel A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bender", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maller", "given" : "Julian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sklar", "given" : "Pamela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "559-75", "title" : "PLINK: a tool set for whole-genome association and population-based linkage analyses.", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "142", "plainTextFormattedCitation" : "142", "previouslyFormattedCitation" : "142" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }142. 175,217 pruned markers were used to calculate coefficients of inbreeding (F) based on observed and expected number of homozygous genotypes. An F-value of >0.2 was used to exclude individuals. No exclusions were made based on this procedure.4.2.4 Ethnic heterogeneity in methylation of known birth weight and length genesThe primary objective was to explore whether ethnic heterogeneity exists in methylation on known birth weight and length genes. This section describes methods used to accomplish this.Identification of known birth weight and length genes: We searched the literature for candidate genes reported in GWA-studies or at a genome-wide significance level (P<5x10-8). Based on this criterion, we identified 12 independent SNPs for birth weight and 18 for birth length (Supplementary Table 4.3). Additionally, though SNPs on IGF1 and IGF2 have not been reported in GWA-studies, evidence from previous methylation studies strongly suggests its role in fetal growthADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJM199610313351805", "ISSN" : "0028-4793", "PMID" : "8857020", "author" : [ { "dropping-particle" : "", "family" : "Woods", "given" : "K A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camacho-H\u00fcbner", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Savage", "given" : "M O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clark", "given" : "A J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England journal of medicine", "id" : "ITEM-1", "issue" : "18", "issued" : { "date-parts" : [ [ "1996", "10", "31" ] ] }, "page" : "1363-7", "title" : "Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene.", "type" : "article-journal", "volume" : "335" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jcem.85.11.6998", "ISSN" : "0021-972X", "PMID" : "11095465", "abstract" : "Experimental rodent studies demonstrate that insulin-like growth factor II (IGF-II) promotes fetal growth, whereas the nonsignaling IGF-II receptor (IGF2R) is inhibitory; in humans their influence is as yet unclear. A soluble, circulating form of IGF2R inhibits IGF-II mediated DNA synthesis and may therefore restrain fetal growth. We measured cord blood levels of IGF-II, soluble IGF2R, insulin, IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and examined their relationships to weight, length, head circumference, ponderal index, and placental weight at birth in 199 normal term singletons. IGF-II levels correlated with levels of IGF-I (r = 0.29; P < 0.0005), IGFBP-3 (r = 0.45; P < 0.0005), and soluble IGF2R (r = 0.20; P < 0.005). Insulin and IGF-I were positively related to all parameters of size at birth. IGF-II was weakly related to ponderal index (r = 0.18; P < 0.05) and placental weight (r = 0.18; P < 0.05), and the molar ratio of IGF-II to IGF2R was also related to birth weight (r = 0.15; P < 0.05). Correlations between the IGFs and size at birth were stronger in nonprimiparous pregnancies; in these, IGF-I (r = 0.52; P < 0.0005), IGFBP-3 (r = 0.41; P < 0.0005), and the IGF-II to IGF2R ratio (r = 0.40; P < 0.0005) were most closely related to placental weight, together accounting for 39% of its variance. We demonstrate for the first time relationships between circulating IGF-II and soluble IGF2R levels and size at birth, supporting their putative opposing roles in human fetal growth.", "author" : [ { "dropping-particle" : "", "family" : "Ong", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kratzsch", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiess", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Costello", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dunger", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2000", "11", "1" ] ] }, "language" : "en", "page" : "4266-9", "publisher" : "Endocrine Society", "title" : "Size at birth and cord blood levels of insulin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and the soluble IGF-II/mannose-6-phosphate receptor in term human infants. The ALSPAC Study Team. Avon Longitudinal Stu", "type" : "article-journal", "volume" : "85" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1056/NEJMoa010107", "ISSN" : "1533-4406", "PMID" : "14657428", "abstract" : "BACKGROUND: Approximately 10 percent of infants with intrauterine growth retardation remain small, and the causes of their growth deficits are often unclear. We postulated that mutations in the gene for the insulin-like growth factor I receptor (IGF-IR) might underlie some cases of prenatal and postnatal growth failure.\n\nMETHODS: We screened two groups of children for abnormalities in the IGF-IR gene. In one group of 42 patients with unexplained intrauterine growth retardation and subsequent short stature, we used single-strand conformation polymorphism analysis, followed by direct DNA sequencing of any abnormalities found. A second cohort consisted of 50 children with short stature who had elevated circulating IGF-I concentrations. Complete sequencing of the IGF-IR gene was performed with DNA from nine children. We also studied a control group of 43 children with normal birth weights.\n\nRESULTS: In the first cohort, we identified one girl who was a compound heterozygote for point mutations in exon 2 of the IGF-IR gene that altered the amino acid sequence to Arg108Gln in one allele and Lys115Asn in the other. Fibroblasts cultured from the patient had decreased IGF-I-receptor function, as compared with that in control fibroblasts. No such mutations were found in the 43 controls. In the second group, we identified one boy with a nonsense mutation (Arg59stop) that reduced the number of IGF-I receptors on fibroblasts. Both children had intrauterine growth retardation and poor postnatal growth.\n\nCONCLUSIONS: Mutations in the IGF-IR gene that lead to abnormalities in the function or number of IGF-I receptors may also retard intrauterine and subsequent growth in humans.", "author" : [ { "dropping-particle" : "", "family" : "Abuzzahab", "given" : "M Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goddard", "given" : "Audrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grigorescu", "given" : "Florin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lautier", "given" : "Corinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keller", "given" : "Eberhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiess", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klammt", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kratzsch", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Osgood", "given" : "Doreen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pf\u00e4ffle", "given" : "Roland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raile", "given" : "Klemens", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seidel", "given" : "Berthold", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Robert J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chernausek", "given" : "Steven D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England journal of medicine", "id" : "ITEM-3", "issue" : "23", "issued" : { "date-parts" : [ [ "2003", "12", "4" ] ] }, "page" : "2211-22", "title" : "IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation.", "type" : "article-journal", "volume" : "349" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "186\u2013188", "plainTextFormattedCitation" : "186\u2013188", "previouslyFormattedCitation" : "186\u2013188" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }186–188. As a result, these two genes were included. Overall, 15 candidate genes for birth weight and 20 genes for birth length were investigated. Selection of CpG probe sites within candidate genes: The Illumina 450k database in R was used to identify CpG probe sites that resided within 100 kilobase pairs of the candidate SNPs. Since no index SNP was available for IGF1 and IGF2, all CpG sites on these genes were included. CpG probe sites with missing data for either study (n=25) and probes previously reported as being sensitive to SNPs (n=51) or cross-reactivity (n=3)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4161/epi.23470", "ISSN" : "1559-2308", "PMID" : "23314698", "abstract" : "DNA methylation, an important type of epigenetic modification in humans, participates in crucial cellular processes, such as embryonic development, X-inactivation, genomic imprinting and chromosome stability. Several platforms have been developed to study genome-wide DNA methylation. Many investigators in the field have chosen the Illumina Infinium HumanMethylation microarray for its ability to reliably assess DNA methylation following sodium bisulfite conversion. Here, we analyzed methylation profiles of 489 adult males and 357 adult females generated by the Infinium HumanMethylation450 microarray. Among the autosomal CpG sites that displayed significant methylation differences between the two sexes, we observed a significant enrichment of cross-reactive probes co-hybridizing to the sex chromosomes with more than 94% sequence identity. This could lead investigators to mistakenly infer the existence of significant autosomal sex-associated methylation. Using sequence identity cutoffs derived from the sex methylation analysis, we concluded that 6% of the array probes can potentially generate spurious signals because of co-hybridization to alternate genomic sequences highly homologous to the intended targets. Additionally, we discovered probes targeting polymorphic CpGs that overlapped SNPs. The methylation levels detected by these probes are simply the reflection of underlying genetic polymorphisms but could be misinterpreted as true signals. The existence of probes that are cross-reactive or of target polymorphic CpGs in the Illumina HumanMethylation microarrays can confound data obtained from such microarrays. Therefore, investigators should exercise caution when significant biological associations are found using these array platforms. A list of all cross-reactive probes and polymorphic CpGs identified by us are annotated in this paper.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "Yi-an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemire", "given" : "Mathieu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choufani", "given" : "Sanaa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butcher", "given" : "Darci T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grafodatskaya", "given" : "Daria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zanke", "given" : "Brent W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gallinger", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hudson", "given" : "Thomas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weksberg", "given" : "Rosanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Epigenetics : official journal of the DNA Methylation Society", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "203-9", "title" : "Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "189", "plainTextFormattedCitation" : "189", "previouslyFormattedCitation" : "189" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }189 were excluded. None of the 7 probes available on ACTBL2 resided within 100 kilobase pairs of the SNP and the only probe available on DCST2 was polymorphic. Furthermore, no CpG probe sites on IGF2 were available. As a result, probe sites on these three genes were not tested. Overall, 216 probe sites on birth weight genes and 308 probe sites on birth length genes were available for analysis.Statistical analysis of selected CpG sites: All analyses were performed using R (version 3.0.2) and PLINK () (version 1.9)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/519795", "ISSN" : "0002-9297", "PMID" : "17701901", "abstract" : "Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.", "author" : [ { "dropping-particle" : "", "family" : "Purcell", "given" : "Shaun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neale", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Todd-Brown", "given" : "Kathe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Lori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Manuel A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bender", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maller", "given" : "Julian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sklar", "given" : "Pamela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bakker", "given" : "Paul I W", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "559-75", "title" : "PLINK: a tool set for whole-genome association and population-based linkage analyses.", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "142", "plainTextFormattedCitation" : "142", "previouslyFormattedCitation" : "142" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }142. The main outcomes of birth weight and length were normally distributed (Supplementary Figure 4.1). Newborn and mother characteristics were compared between the ethnic groups using an independent sample’s t-test. Linear regression analyses were conducted to test the association between percent methylation at CpG sites identified above with birth weight / lengthADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrg3273", "ISSN" : "1471-0064", "PMID" : "22986265", "abstract" : "DNA methylation is an epigenetic mark that has suspected regulatory roles in a broad range of biological processes and diseases. The technology is now available for studying DNA methylation genome-wide, at a high resolution and in a large number of samples. This Review discusses relevant concepts, computational methods and software tools for analysing and interpreting DNA methylation data. It focuses not only on the bioinformatic challenges of large epigenome-mapping projects and epigenome-wide association studies but also highlights software tools that make genome-wide DNA methylation mapping more accessible for laboratories with limited bioinformatics experience.", "author" : [ { "dropping-particle" : "", "family" : "Bock", "given" : "Christoph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2012", "10" ] ] }, "page" : "705-19", "title" : "Analysing and interpreting DNA methylation data.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "175", "plainTextFormattedCitation" : "175", "previouslyFormattedCitation" : "175" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }175. Due to marked difference in global methylation observed between the two cohorts (Supplementary Table 4.4), all analyses were conducted separately for South Asians and white Caucasians. Heterogeneity in the effect of methylation on birth weight / length between ethnicities was assessed using Cochran’s Q statistic based on a fixed effects meta-analysis. To correct for multiple testing, we used the false-discovery rate (FDR) procedure to estimate q values; associations with a q value of 0.05 or less were considered statistically significantADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(13)62674-4", "ISSN" : "1474-547X", "PMID" : "24630777", "abstract" : "BACKGROUND: Obesity is a major health problem that is determined by interactions between lifestyle and environmental and genetic factors. Although associations between several genetic variants and body-mass index (BMI) have been identified, little is known about epigenetic changes related to BMI. We undertook a genome-wide analysis of methylation at CpG sites in relation to BMI.\n\nMETHODS: 479 individuals of European origin recruited by the Cardiogenics Consortium formed our discovery cohort. We typed their whole-blood DNA with the Infinium HumanMethylation450 array. After quality control, methylation levels were tested for association with BMI. Methylation sites showing an association with BMI at a false discovery rate q value of 0\u00b705 or less were taken forward for replication in a cohort of 339 unrelated white patients of northern European origin from the MARTHA cohort. Sites that remained significant in this primary replication cohort were tested in a second replication cohort of 1789 white patients of European origin from the KORA cohort. We examined whether methylation levels at identified sites also showed an association with BMI in DNA from adipose tissue (n=635) and skin (n=395) obtained from white female individuals participating in the MuTHER study. Finally, we examined the association of methylation at BMI-associated sites with genetic variants and with gene expression.\n\nFINDINGS: 20 individuals from the discovery cohort were excluded from analyses after quality-control checks, leaving 459 participants. After adjustment for covariates, we identified an association (q value \u22640\u00b705) between methylation at five probes across three different genes and BMI. The associations with three of these probes--cg22891070, cg27146050, and cg16672562, all of which are in intron 1 of HIF3A--were confirmed in both the primary and second replication cohorts. For every 0\u00b71 increase in methylation \u03b2 value at cg22891070, BMI was 3\u00b76% (95% CI 2\u00b74-4\u00b79) higher in the discovery cohort, 2\u00b77% (1\u00b72-4\u00b72) higher in the primary replication cohort, and 0\u00b78% (0\u00b72-1\u00b74) higher in the second replication cohort. For the MuTHER cohort, methylation at cg22891070 was associated with BMI in adipose tissue (p=1\u00b772\u2008\u00d7\u200810(-5)) but not in skin (p=0\u00b7882). We observed a significant inverse correlation (p=0\u00b7005) between methylation at cg22891070 and expression of one HIF3A gene-expression probe in adipose tissue. Two single nucleotide polymorphisms--rs8102595 and rs3826795--had independent ass\u2026", "author" : [ { "dropping-particle" : "", "family" : "Dick", "given" : "Katherine J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nelson", "given" : "Christopher P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsaprouni", "given" : "Loukia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandling", "given" : "Johanna K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "A\u00efssi", "given" : "Dylan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wahl", "given" : "Simone", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meduri", "given" : "Eshwar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morange", "given" : "Pierre-Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gagnon", "given" : "France", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waldenberger", "given" : "Melanie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdmann", "given" : "Jeanette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hengstenberg", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cambien", "given" : "Francois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodall", "given" : "Alison H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouwehand", "given" : "Willem H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schunkert", "given" : "Heribert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Tim D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tr\u00e9gou\u00ebt", "given" : "David-Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samani", "given" : "Nilesh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9933", "issued" : { "date-parts" : [ [ "2014", "6", "7" ] ] }, "page" : "1990-8", "title" : "DNA methylation and body-mass index: a genome-wide analysis.", "type" : "article-journal", "volume" : "383" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "185", "plainTextFormattedCitation" : "185", "previouslyFormattedCitation" : "185" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }185. For seven sites showing significant ethnic heterogeneity on birth weight from the primary analysis, an investigation of genetic confounding was carried out to assess whether observed associations between birth weight / length and methylation levels at CpG sites were a result of adjacent SNPs being correlated with both methylation and birth weight / lengthADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/gb-2011-12-1-r10", "ISSN" : "1465-6914", "PMID" : "21251332", "abstract" : "BACKGROUND: DNA methylation is an essential epigenetic mechanism involved in gene regulation and disease, but little is known about the mechanisms underlying inter-individual variation in methylation profiles. Here we measured methylation levels at 22,290 CpG dinucleotides in lymphoblastoid cell lines from 77 HapMap Yoruba individuals, for which genome-wide gene expression and genotype data were also available.\n\nRESULTS: Association analyses of methylation levels with more than three million common single nucleotide polymorphisms (SNPs) identified 180 CpG-sites in 173 genes that were associated with nearby SNPs (putatively in cis, usually within 5 kb) at a false discovery rate of 10%. The most intriguing trans signal was obtained for SNP rs10876043 in the disco-interacting protein 2 homolog B gene (DIP2B, previously postulated to play a role in DNA methylation), that had a genome-wide significant association with the first principal component of patterns of methylation; however, we found only modest signal of trans-acting associations overall. As expected, we found significant negative correlations between promoter methylation and gene expression levels measured by RNA-sequencing across genes. Finally, there was a significant overlap of SNPs that were associated with both methylation and gene expression levels.\n\nCONCLUSIONS: Our results demonstrate a strong genetic component to inter-individual variation in DNA methylation profiles. Furthermore, there was an enrichment of SNPs that affect both methylation and gene expression, providing evidence for shared mechanisms in a fraction of genes.", "author" : [ { "dropping-particle" : "", "family" : "Bell", "given" : "Jordana T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pai", "given" : "Athma A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pickrell", "given" : "Joseph K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaffney", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pique-Regi", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Degner", "given" : "Jacob F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilad", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pritchard", "given" : "Jonathan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genome biology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "R10", "title" : "DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "190", "plainTextFormattedCitation" : "190", "previouslyFormattedCitation" : "190" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }190. An additive model of inheritance for the SNPs was assumed. We report both the unadjusted association between CpG sites and birth weight / length, and an adjusted association for gestational age, newborn sex, and genotype. Additionally, we assessed whether selected SNPs (or proxies, Supplementary Table 4.5 and 4.6) were associated with birth weight / length in our sample and if ethnic heterogeneity in this association was present. To accomplish this, we tested the association of a genotype score with the respective outcome. Genotype data was available for nine of the 12 chosen birth weight SNPs and nine of the 18 birth length SNPs from both cohorts. A genotype score was also created for both traits. For each SNP, the weight/length-reducing allele was used as the risk allele. Genotypes were coded as 0, 1, and 2, designating copies of the risk allele. The un-weighted genotype score was calculated for each individual by allele counting. Exploring sources of heterogeneity: The primary analysis revealed ethnic heterogeneity in the effect of methylation on birth weight. To preclude the possibility that this heterogeneity stemmed from technical or other biological variation, we conducted the following investigations. The CHILD offers a unique opportunity to investigate possible sources of heterogeneity as a small number of individuals in this cohort were of South Asian descent. As these individuals were recruited and their samples processed in the same manner as the white Caucasians included in our analysis, we were able to investigate whether observed ethnic differences were true or result from variation between the cohorts. Firstly, as leukocytes and erythrocytes in blood can vary in methylation levels, we investigated whether differences in cell type existed between South Asians and white Caucasians that can manifest as differences in the effect of methylation. Additionally, there were some differences in the blood collection protocols for the START and CHILD cohorts, which may have impacted the relationship between methylation and the outcomes tested. The main protocol variations are highlighted in Supplementary Table 4.7. To this end, we (1) investigated the relationship between methylation and birth weight for both South Asians and white Caucasians in the CHILD cohort as data on a small number of South Asians were available in this cohort; and (2) assessed the effect of processing time on methylation levels in the CHILD cohort, as this was among the key protocol differences between the START and CHILD cohorts.4.2.5 Regional analysis of significant sitesCpG sites can be highly correlated with neighboring sites and may occur within clusters that are co-regulatedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/bioinformatics/btt498", "ISSN" : "1367-4803", "PMID" : "23990415", "abstract" : "MOTIVATION: DNA methylation is a heritable modifiable chemical process that affects gene transcription and is associated with other molecular markers (e.g. gene expression) and biomarkers (e.g. cancer or other diseases). Current technology measures methylation in hundred of thousands, or millions of CpG sites throughout the genome. It is evident that neighboring CpG sites are often highly correlated with each other, and current literature suggests that clusters of adjacent CpG sites are co-regulated.\n\nRESULTS: We develop the Adjacent Site Clustering (A-clustering) algorithm to detect sets of neighboring CpG sites that are correlated with each other. To detect methylation regions associated with exposure, we propose an analysis pipeline for high-dimensional methylation data in which CpG sites within regions identified by A-clustering are modeled as multivariate responses to environmental exposure using a generalized estimating equation approach that assumes exposure equally affects all sites in the cluster. We develop a correlation preserving simulation scheme, and study the proposed methodology via simulations. We study the clusters detected by the algorithm on high dimensional dataset of peripheral blood methylation of pesticide applicators.\n\nAVAILABILITY: We provide the R package Aclust that efficiently implements the A-clustering and the analysis pipeline, and produces analysis reports. The package is found on \n\nCONTACT: tsofer@hsph.harvard.edu", "author" : [ { "dropping-particle" : "", "family" : "Sofer", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schifano", "given" : "E. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoppin", "given" : "J. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hou", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baccarelli", "given" : "A. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Bioinformatics", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2013", "8", "29" ] ] }, "page" : "2884-2891", "title" : "A-clustering: a novel method for the detection of co-regulated methylation regions, and regions associated with exposure", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "174", "plainTextFormattedCitation" : "174", "previouslyFormattedCitation" : "174" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }174. Therefore, for each CpG site that was found to be significant in our primary analysis?(Section 4.2.4), we conducted an additional?regional analysis whereby the presence of a CpG cluster and its effect on the phenotype was investigated.??Identification of correlated sites:?The Illumina 450k database was used to identify known CGI. For?sites for where CGI have not been previously identified or existence of a cluster is not known, a correlation with neighboring sites with Pearson’s r ≥0.5 was used to establish a CpG clusterADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/nar/gks928", "ISSN" : "1362-4962", "PMID" : "23066096", "abstract" : "Methylation of a CpG island is a faithful marker of silencing of its associated gene. Different approaches report the methylation status of a CpG island based on the determination of one or a few CpG sites by assuming the homogeneity of methylation along the element. This strategy is frequently applied in both locus-specific and genome-wide studies, but often without a validation of the representativeness of the interrogated CpG site compared with the whole element. We have evaluated the predictive informativeness of the HpaII sites located in CpG islands using data from high-resolution methylome maps, which offer the possibility to assess the methylation homogeneity of each CpG island and to determine the reporter accuracy of single sites as surrogate markers. An excellent correlation was observed between the HpaII and CpG island methylation levels (r > 0.93). At the qualitative level, the predictive sensitivity of HpaII was >95% with >92% specificity for methylated CpG islands and >90% sensitivity with >95% specificity for unmethylated CpG islands. This analysis provides a global validation framework for strategies based on the use of the methylation-sensitive HpaII restriction enzyme.", "author" : [ { "dropping-particle" : "", "family" : "Barrera", "given" : "V\u00edctor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peinado", "given" : "Miguel A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nucleic acids research", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2012", "12", "12" ] ] }, "page" : "11490-8", "title" : "Evaluation of single CpG sites as proxies of CpG island methylation states at the genome scale.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "173", "plainTextFormattedCitation" : "173", "previouslyFormattedCitation" : "173" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }173.?Statistical analysis: Within each cluster, the percent methylation for all CpG sites?was averaged; the average percent methylation was then used as a predictor for birth weight. The analysis was?adjusted for gestational age, sex, and genotype. For each cluster,?analyses were conducted separately in South Asians and white Caucasians, and heterogeneity in the effect sizes between ethnic groups was assessed.4.2.6 Genome-wide methylation for birth weight in South AsiansSince the primary analysis consistently found CpG sites were associated with birth weight in white Caucasians, but not South Asians, we conducted an agnostic search in the START cohort to investigate whether novel CpG sites were associated with birth weight in South Asians.Selection of CpG probe sites: After quality control, 465,575 CpG probe sites were available from the Ilumina Methylation BeadChip in the START cohort, as described earlier (Section 4.2.3). We further excluded CpG sites known to be polymorphic and/or cross-reactive (n=91,698), leaving 373,877 CpG sites for analysis. Statistical analysis: Linear regression was performed between percent methylation at CpG probe sites and birth weight. The genome-wide analysis was adjusted for gestational age and sex. To correct for multiple comparisons, a genome-wide significance level of 1.3x10-7 was used, determined according to the Bonferroni procedure. Similar to previous genome-wide analyses, a second ‘suggestive’ threshold (P<1x10-5) was setADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1534/genetics.110.120907", "ISSN" : "1943-2631", "PMID" : "21115973", "abstract" : "Enormous progress in mapping complex traits in humans has been made in the last 5 yr. There has been early success for prevalent diseases with complex phenotypes. These studies have demonstrated clearly that, while complex traits differ in their underlying genetic architectures, for many common disorders the predominant pattern is that of many loci, individually with small effects on phenotype. For some traits, loci of large effect have been identified. For almost all complex traits studied in humans, the sum of the identified genetic effects comprises only a portion, generally less than half, of the estimated trait heritability. A variety of hypotheses have been proposed to explain why this might be the case, including untested rare variants, and gene-gene and gene-environment interaction. Effort is currently being directed toward implementation of novel analytic approaches and testing rare variants for association with complex traits using imputed variants from the publicly available 1000 Genomes Project resequencing data and from direct resequencing of clinical samples. Through integration with annotations and functional genomic data as well as by in vitro and in vivo experimentation, mapping studies continue to characterize functional variants associated with complex traits and address fundamental issues such as epistasis and pleiotropy. This review focuses primarily on the ways in which genome-wide association studies (GWASs) have revolutionized the field of human quantitative genetics.", "author" : [ { "dropping-particle" : "", "family" : "Stranger", "given" : "Barbara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stahl", "given" : "Eli A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raj", "given" : "Towfique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011", "2", "1" ] ] }, "page" : "367-83", "title" : "Progress and promise of genome-wide association studies for human complex trait genetics.", "type" : "article-journal", "volume" : "187" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "191", "plainTextFormattedCitation" : "191", "previouslyFormattedCitation" : "191" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }191.4.3 ResultsAs shown in Table 4.1, some differences in baseline physical characteristics between South Asians and white Caucasians were evident. Briefly, South Asian newborns were lower birth weight, had a greater birth length, and a lower gestational age than white Caucasians. Ethnic differences in birth weight and length persisted after adjustment for gestational age and sex (P for birth weight = 8.61x10-9; P for birth length = 1.59x10-4 after adjustment). Additionally, South Asian mothers were younger, had a lower pre-pregnancy BMI, were less likely to be smokers, but had a higher prevalence of gestational diabetes and hypertension during pregnancy.Table 4. SEQ Table_4. \* ARABIC 1 Descriptive characteristics of included participants stratified by ethnicitySouth Asian (n=234)White Caucasian (n=250)PMean (SD) / %Mean (SD) / %NewbornsBirth weight (in kg)3.21 (0.51)3.48 (0.48)7.73x10-9Birth length (in cm)52.22 (2.89)51.41 (2.72)3.68x10-3Gestational age (weeks)38.96 (1.48)39.17 (1.35)9.58x10-2% Female50.0%44.0%1.93x10-1MothersAge (years)29.96 (4.05)32.53 (4.54)1.30x10-10Gestational weight gain (in kg)*13.28 (5.97)15.14 (5.93)3.35x10-3Pre-pregnancy BMI (in kg/m2)**23.87 (4.66)24.14 (6.68)6.73x10-1% Gestational diabetes17.5%?5.20%?1.31x10-3% Smokers0%2.83%7.89x10-3% Hypertension during pregnancy4.32%1.65%8.86x10-2* Available in n=146 White Caucasians** Available in n=141 White Caucasians? Established using self-report and diagnosis using an OGTT? Established using self-report (OGTT data was not available from the CHILD cohort)4.3.1 Ethnic heterogeneity in methylation at known birth weight and length genesBirth weightWe first conducted an unadjusted analysis of methylation at CpG sites (specified in the methods, Section 4.2.4) and birth weight. Thirty-seven out of the 216 CpG sites that were investigated showed nominal evidence of ethnic heterogeneity (P heterogeneity <0.05) in the association between methylation and birth weight. After adjusting for multiple testing using the FDR procedure, seven of these CpG sites still showed significant ethnic heterogeneity (Table 4.2). These included CpG sites in TCF7L2 on chromosome 10, CALCR on chromosome 7, CDKAL1 on chromosome 6, IGF1 on chromosome 12, and HMGA2 on chromosome 12. Among white Caucasians, six of these seven sites (TCF7L2 cg09022607, CALCR cg23061150, IGF1 cg01305421, HMGA2 cg24776736, TCF7L2 cg11748187, and CDKAL1 cg06512263) were associated with birth weight after an FDR correction, while none were significantly associated with birth weight in South Asians.While increasing methylation demonstrated a positive relationship with birth weight among South Asians, it led to a decrease in birth weight in white Caucasians, indicating the presence of a quantitative interaction. Methylation at HMGA2 cg24892571 showed the largest change in birth weight among South Asians – a 10 percent increase in methylation led to a 0.6 kg higher birth weight (Table 4.2). In white Caucasians, methylation of cg09022607 on TCF7L2 had the greatest impact on birth weight; specifically, a decrease in birth weight of 0.4 kg for every 10 percent increase in methylation. Average methylation at all seven sites is summarized in Table 4.3. Notably, white Caucasians were consistently hypo-methylated at all sites compared to South Asians. Table 4. SEQ Table_4. \* ARABIC 2 Association between percent methylation at sites showing ethnic variation for birth weight in cord-blood DNA GeneCpG siteBase pair positionModelSouth AsianWhite CaucasiansP heterogeneityβ-coefficient?Pβ-coefficient?PTCF7L2cg09022607114712695Unadjusted0.111.70x10-1-0.371.51x10-52.72x10-5Adjusted0.054.03x10-1-0.213.46x10-22.46x10-2CALCRcg2306115093181353Unadjusted0.267.71x10-3-0.269.70x10-42.82x10-5Adjusted0.182.79x10-2-0.237.41x10-34.78x10-4HMGA2cg2489257166284828Unadjusted0.579.55x10-4-0.207.87x10-21.64x10-4Adjusted0.451.56x10-3-0.123.22x10-12.13x10-3HMGA2cg2477673666356357Unadjusted0.082.40x10-1-0.221.97x10-53.43x10-4Adjusted0.044.28x10-1-0.132.95x10-23.34x10-2TCF7L2cg11748187114713108Unadjusted0.091.09x10-1-0.161.36x10-36.80x10-4Adjusted0.034.47x10-1-0.106.18x10-25.12x10-2IGF1cg01305421102874286Unadjusted0.082.10x10-1-0.231.68x10-43.40x10-4Adjusted*0.017.63x10-1-0.156.64x10-42.39x10-2CDKAL1cg0651226320709867Unadjusted0.053.06x10-1-0.176.40x10-41.31x10-3Adjusted0.034.74x10-1-0.062.92x10-12.02x10-1* IGF1 cg01305421 was only adjusted for gestational age and sex ? β-coefficients are reported as change in birth weight (in kg) for a 10% increase in methylation at the respective CpG probe siteTable 4. SEQ Table_4. \* ARABIC 3 Percent methylation at the seven sites showing ethnic heterogeneity in the primary analysisGeneCpG siteAverage percent methylation (interquartile range)South AsiansWhite CaucasiansTCF7L2cg0902260733% (30% - 36%)29% (27% - 31%)TCF7L2cg1174818744% (40% - 48%)37% (33% - 41%)CALCRcg2306115086% (84% - 88%)82% (79% - 84%)HMGA2cg2489257190% (89% - 91%)86% (84% - 88%)HMGA2cg2477673666% (62% - 70%)59% (54% - 63%)CDKAL1cg0651226334% (29% - 39%)27% (23% - 31%)IGF1cg0130542127% (22% - 31%)19% (16% - 22%)Of the seven CpG sites showing ethnic heterogeneity, the CpG sites on TCF7L2 and HMGA2 were correlated with other sites on those genes. The two CpG sites on TCF7L2 are neighbouring sites in the body of the gene. Methylation levels at cg11748187 and cg09022607 were highly correlated with each other (Pearson’s r=0.767 and 0.782 in the CHILD and START cohorts, respectively). Similarly, on HMGA2, cg24892571 and cg24776736 were weakly correlated neighboring probes (Pearson’s r=0.386 in the CHILD cohort and 0.420 in the START cohort).Confounding and adjustment for covariatesGenetic confounding: Genetic confounding can result if genotype variation at SNPs is correlated with both methylation levels at nearby CpG sites and the phenotype. Conversely, the SNP can also be causal in the association with the phenotypeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0014040", "ISSN" : "1932-6203", "PMID" : "21124985", "abstract" : "Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D), focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip) and absolute methylation values were estimated using a Bayesian algorithm (BATMAN). Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p\u200a=\u200a9.40\u00d710(-4), permutation p\u200a=\u200a1.0\u00d710(-3)). Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p\u200a=\u200a1.13\u00d710(-7)). Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM), encapsulates a Highly Conserved Non-Coding Element (HCNE) that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA) SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.", "author" : [ { "dropping-particle" : "", "family" : "Bell", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finer", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Gareth A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rakyan", "given" : "Vardhman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teschendorff", "given" : "Andrew E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akan", "given" : "Pelin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stupka", "given" : "Elia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Down", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morison", "given" : "Ian M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mill", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pidsley", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beck", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "1", "18" ] ] }, "page" : "e14040", "publisher" : "Public Library of Science", "title" : "Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "192", "plainTextFormattedCitation" : "192", "previouslyFormattedCitation" : "192" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }192. To investigate presence of genetic confounding, we tested whether SNPs on TCF7L2, CALCR, HMGA2, and CDKAL1 were associated with percent methylation at the related CpG site and birth weight. We then examined whether any ethnic heterogeneity in these associations existed (Table 4.4). It should be noted that genetic confounding at IGF1 cg01305421 was not tested, as a SNP associated with birth weight on this gene has not been reported from GWA-studies. Of the SNPs tested, rs4132670 and rs10784502 appeared to be associated with methylation levels at nearby CpG sites. Variation in methylation of cg11748187 by genotype of rs4132670 on TCF7L2 was significant in white Caucasians, but not South Asians (P heterogeneity=2.99x10-2). Genetic variation on rs4132670 explained 4.04% of the variation in methylation at cg11748187 in white Caucasians, and as expected, explained none of the variation in South Asians. Additionally, methylation at cg24776736 on HMGA2 was significantly associated with rs10784502 in both South Asians and white Caucasians. Though this association explained 4.44% of the variation in methylation at cg24776736 in Caucasians and only 1.97% in South Asians, there was no statistically significant ethnic heterogeneity. Given the association of these two SNPs with methylation, we next needed to test whether the SNPs were associated with birth weight to uncover genetic confounding. Similar to the relationship of the SNP with methylation, we found that TCF7L2 rs4132670 was associated with birth weight in Caucasians, suggesting a possibility for genetic confounding at this site. The SNP was not associated with birth weight in South Asians. HMGA2 rs10784502, on the other hand, was not associated with birth weight in either ethnicity. An important consideration is that the power of these analyses was quite low (Supplementary Table 4.5). Confounding from gestational age and sex: No substantial differences were evident for percent methylation at any of the seven sites between males and females or by gestational age in South Asians. Conversely, in female Caucasians, percent methylation was significantly lower compared to males at 4 sites (IGF1 cg01305421, CDKAL1 cg06512263 and both cg09022607 and cg11748187 on TCF7L2). Furthermore, 5 sites also varied by gestational age in white Caucasians; with the percent methylation at IGF-1 cg01305421, HMGA2 cg24776736, TCF7L2 cg11748187 and cg09022607, and CDKAL1 cg06512263 lower in newborns with a gestational age ≥ 39 weeks.Adjustment for confounders: To account for possible confounding by gestational age, sex, and genotype, the models for each CpG–birth weight pair were recalculated after adjustment in both ethnic groups. After adjustment, significant heterogeneity between ethnic groups persisted at five of the seven sites (IGF1 cg01305421, TCF7L2 cg09022607, CALCR cg23061150, HMGA2 cg24776736 and cg24892571). After adjustment for gestational age, sex, and genotype, percent methylation at TCF7L2 cg11748187, CDKAL1 cg06512263, and HMGA2 cg24892571 was no longer significantly associated with birth weight in white Caucasians. Because HMGA2 cg24892571 remained nominally significant among South Asians, ethnic heterogeneity at this site persisted. For the other two sites, it appears that a combination of gestational age, sex, and genotype explains variation in birth weight and as such there is no ethnic heterogeneity in the effect of methylation after adjustment for these confounders, i.e. methylation status is no longer associated with outcome in either ethnic group. Exploring sources of heterogeneityVariation in cell-type composition: Differences in the composition of leukocytes and erythrocytes by ethnicity was investigated in the CHILD cohort as this data was available for both ethnic groups. Results are presented in Supplementary Table 4.8 and suggest no statistically significant differences between South Asians and white Caucasians.Methylation-birth weight relationship in South Asians of the CHILD cohort: To investigate whether the discordance in direction of effect for methylation on birth weight between South Asians and white Caucasians was a result of between-study differences, we assessed the seven sites in a sample of 18 South Asian newborns available from the CHILD cohort. Our analyses revealed that at five out of the seven sites, an increase in methylation led to a decrease in birth weight, consistent with white Caucasians from CHILD (Supplementary Table 4.9). Though, it should be noted, this was not evident at all CpG sites and was based only on a sample of 18 individuals. Effect of processing time on methylation: Among the most notable protocol differences between the START and CHILD cohorts is the time elapsed between collection and processing of the samples. In the START cohort, this time was less than or equal to 2 hours, while in the CHILD cohort, the time stipulation was 24 hours, with an average of 19.8 hours. To this end, we first investigated whether processing time affected methylation levels. A statistically significant relationship between methylation and processing time was evident for only one CpG site among the seven tested; methylation at TCF7L2 cg11748187 was associated with processing time with a P-value of 4.86x10-5. Methylation at the remaining six sites did not show any relationship with processing time (Supplementary Table 4.10). Secondly, we stratified the CHILD samples by processing time (greater than 2 hours elapsed versus less than or equal to 2 hours) and compared the relationship between methylation at the seven CpG sites and birth weight in the sub-groups. The results are presented in Supplementary Table 4.11. While not statistically significant, methylation at three of the seven sites in the less than 2-hour subgroup showed a positive relationship with birth weight, congruent with results from the START cohort. This lends some support to the speculation that differences in processing time may be responsible for the observed discordance in the direction of effect between South Asians and white Caucasians.Birth lengthNo CpG sites showed evidence of ethnic heterogeneity after correction for multiple testing using a FDR q value of 0.05. As no sites were significant in our primary analysis, we did not carry out any further analyses (i.e. regional or genome-wide analyses) for this phenotype. Additionally, our genetic analysis revealed that no individual SNPs or the genotype score of birth length SNPs was associated with the trait in either ethnic group (Supplementary Table 4.6). The power for these analyses, however, was very low.Table 4. SEQ Table_4. \* ARABIC 4 Association between methylation level and SNP on birth weight genesGeneSNP ?Risk alleleCpG site% Methylationβ-coefficient ?PP heterogeneity TCF7L2rs4132670Gcg09022607GGGAAASouth Asians33.0533.1132.790.059.21 x10-14.74 x10-1White Caucasians28.9629.5129.60-0.383.23 x10-1cg11748187GGGAAASouth Asians44.0144.2043.07-0.197.73 x10-12.99 x10-2 *White Caucasians36.3738.4239.841.835.92 x10-3 *CALCRrs6968642Gcg23061150GGGAAASouth Asians86.1985.9685.520.313.29 x10-11.24 x10-1White Caucasians81.3281.9382.19-0.452.36 x10-1HMGA2rs10784502Acg24892571GGGAAASouth Asians89.5289.6789.800.144.97 x10-16.00 x10-1White Caucasians85.8785.8685.27-0.322.61 x10-1cg24776736GGGAAASouth Asians62.4665.9766.151.113.25 x10-2 *3.86 x10-1White Caucasians56.6160.0960.441.813.79 x10-3 *CDKAL1rs9368222Acg06512263CCCAAASouth Asians34.5833.5434.86-0.435.72 x10-17.33 x10-1White Caucasians28.1127.4526.32-0.79x10-1? Proxy SNPs are presented here; Lead SNPs are available in Supplementary Table 4.2? β-coefficients represent percent change in methylation for each risk allele* P < 0.054.3.2 Regional analysis of significant sitesAs neighboring CpG sites can be correlated and co-regulated, we conducted a regional analysis whereby the effect of CpG clusters (neighboring sites with Pearson’s r ≥0.5) on birth weight was investigated in both ethnic groups. Only CpG sites on TCF7L2 and CALCR showed significant correlations with neighboring sites. CpG sites near IGF1 cg01305421, HMGA2 cg24776736 and cg24892571 as well as CDKAL1 cg06512263 were not greatly correlated and therefore regional analyses on these sites were not performed. The two probe sites on TCF7L2 are located on the south shore of a known CGI that spans from bp114712115 and bp114712544 on Chromosome 10. Consequently, percent methylation at sites encompassed in this region was averaged. These included cg04557665, cg09022607, cg27162705, and cg11748187. A 10 percent increase in the average methylation at these 4 sites led to a 0.1 kg increase in birth weight for South Asians, and 0.2 kg decrease for white Caucasians. Four CpG probe sites (cg12970937, cg20696338, cg13916255, and cg07123608) neighboring cg23061150 on CALCR had a Pearson’s r ≥ 0.5 (Figure 4.1). However, the effect of the average methylation across these four sites was not statistically associated with birth weight in either ethnicity (Table 4.5). Figure 4. SEQ Figure_4. \* ARABIC 1 Plots of Pearson’s r correlations for CpG sites on TCF7L2 and CALCR in white Caucasians and South Asians036957000(a) CpG sites on TCF7L2 in white Caucasians (left) and South Asians (right)(b) CpG sites on CALCR in white Caucasians (left) and South Asians (right)04191000Table 4. SEQ Table_4. \* ARABIC 5 Regional analysis of significant CpG sites in South Asians and white CaucasiansGeneSouth AsiansWhite CaucasiansP heterogeneityβ-coefficient *Pβ-coefficient *PTCF7L2 ?0.063.68 x10-1-0.212.48x10-21.92x10-2CALCR ?0.148.18x10-2-0.225.31x10-29.06x10-3* β-coefficients are reported as change in birth weight (in kg) for a 10% increase in methylation at the respective CpG probe site? Methylation was averaged over the following sites: cg04557665, cg09022607, cg27162705, and cg11748187 ? Methylation was averaged over the following sites: cg12970937, cg20696338, cg13916255, cg07123608, and cg230611504.3.3 Genome-wide methylation for birth weight in South AsiansAs the primary analysis of ethnic heterogeneity revealed that methylation of CpG sites on known birth weight genes were not associated with the phenotype in South Asians, we conducted a genome-wide search in this group. Associations between methylation at CpG probe sites with birth weight were adjusted for gestational age and sex. After Bonferroni correction, none of the sites were significant at the genome-wide threshold of P<1.3x10-7, however three sites showed suggestive significance (P<1x10-5) (Figure 4.2). These included probe site cg07605236 on SFXN5 (P=5.20x10-6), cg20408693 on SLC38A2 (P=8.76x10-6), and cg06032483 on a gene on chromosome 8 (P=6.65x10-6). Average methylation values for cg06032483, cg07605236, and cg20408693 were 90.0%, 91.9%, 6.5% in South Asians, respectively. A Q-Q plot of the P-values from the GWA-study of methylation sites was generated (Figure 4.3). We then investigated the association of these sites in white Caucasians; none were associated with birth weight in this group (Table 4.6).Figure 4. SEQ Figure_4. \* ARABIC 2 Manhattan plot showing the distribution of P values of the association between methylation probes and birth weight in South AsiansTable 4. SEQ Table_4. \* ARABIC 6 Association between percent methylation on CpG sites associated at P<1x10-5 with birth weight in South AsiansGeneCpG siteSouth AsiansWhite Caucasiansβ-coefficient ?Pβ-coefficient ?PSFXN5cg076052360.915.20x10-6-0.047.54x10-1NAcg060324830.466.65x10-6-0.046.18x10-1SLC38A2cg204086931.348.76x10-6-0.302.44x10-1? β-coefficients are reported as change in birth weight (in kg) for a 10% increase in methylation at the respective CpG probe siteFigure 4. SEQ Figure_4. \* ARABIC 3 Q-Q plot of P-values acquired from GWA-studies of CpG sites 4.4 DiscussionOur investigation demonstrates significant ethnic heterogeneity in methylation levels of birth weight genes comparing South Asians and white Caucasians. We report seven CpG probe sites on TCF7L2, CALCR, IGF1, HMGA2, and CDKAL1 at which percent methylation is robustly associated with birth weight in white Caucasians, but not in South Asians. We also report three sites associated with birth weight in South Asians at a genome-wide P < 1x10-5. These three sites were not associated with birth weight in white Caucasians. None of the sites tested were robustly associated with birth length in either cohort and did not show ethnic heterogeneity. Although some previous studies have assessed methylation profiles for birth weightADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1755-8794-5-10", "ISSN" : "1755-8794", "PMID" : "22498030", "abstract" : "BACKGROUND: Infant birth weight is a complex quantitative trait associated with both neonatal and long-term health outcomes. Numerous studies have been published in which candidate genes (IGF1, IGF2, IGF2R, IGF binding proteins, PHLDA2 and PLAGL1) have been associated with birth weight, but these studies are difficult to reproduce in man and large cohort studies are needed due to the large inter individual variance in transcription levels. Also, very little of the trait variance is explained. We decided to identify additional candidates without regard for what is known about the genes. We hypothesize that DNA methylation differences between individuals can serve as markers of gene \"expression potential\" at growth related genes throughout development and that these differences may correlate with birth weight better than single time point measures of gene expression.\n\nMETHODS: We performed DNA methylation and transcript profiling on cord blood and placenta from newborns. We then used novel computational approaches to identify genes correlated with birth weight.\n\nRESULTS: We identified 23 genes whose methylation levels explain 70-87% of the variance in birth weight. Six of these (ANGPT4, APOE, CDK2, GRB10, OSBPL5 and REG1B) are associated with growth phenotypes in human or mouse models. Gene expression profiling explained a much smaller fraction of variance in birth weight than did DNA methylation. We further show that two genes, the transcriptional repressor MSX1 and the growth factor receptor adaptor protein GRB10, are correlated with transcriptional control of at least seven genes reported to be involved in fetal or placental growth, suggesting that we have identified important networks in growth control. GRB10 methylation is also correlated with genes involved in reactive oxygen species signaling, stress signaling and oxygen sensing and more recent data implicate GRB10 in insulin signaling.\n\nCONCLUSIONS: Single time point measurements of gene expression may reflect many factors unrelated to birth weight, while inter-individual differences in DNA methylation may represent a \"molecular fossil record\" of differences in birth weight-related gene expression. Finding these \"unexpected\" pathways may tell us something about the long-term association between low birth weight and adult disease, as well as which genes may be susceptible to environmental effects. These findings increase our understanding of the molecular mechanisms involved in human development an\u2026", "author" : [ { "dropping-particle" : "", "family" : "Turan", "given" : "Nahid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghalwash", "given" : "Mohamed F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katari", "given" : "Sunita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coutifaris", "given" : "Christos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Obradovic", "given" : "Zoran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sapienza", "given" : "Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genomics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "10", "title" : "DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease?", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1559-2308", "PMID" : "21521940", "abstract" : "Birthweight has been associated with a number of health outcomes throughout life. Crucial to proper infant growth and development is the placenta, and alterations to placental gene function may reflect differences in the intrauterine environment which functionally contribute to infant growth and may ultimately affect the child's health. To examine if epigenetic alteration to the glucocorticoid receptor (GR) gene was linked to infant growth, we analyzed 480 human placentas for differential methylation of the GR gene exon 1F and examined how this variation in methylation extent was associated with fetal growth. Multivariable linear regression revealed a significant association (p < 0.0001) between differential methylation of the GR gene and large for gestational age (LGA) status. Our work is one of the first to link infant growth as a measure of the intrauterine environment and epigenetic alterations to the GR and suggests that DNA methylation may be a critical determinant of placental function.", "author" : [ { "dropping-particle" : "", "family" : "Filiberto", "given" : "Amanda C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maccani", "given" : "Matthew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koestler", "given" : "Devin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilhelm-Benartzi", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avissar-Whiting", "given" : "Michele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banister", "given" : "Carolyn E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gagne", "given" : "Luc A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marsit", "given" : "Carmen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Epigenetics : official journal of the DNA Methylation Society", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "566-72", "title" : "Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.metabol.2013.10.003", "ISSN" : "1532-8600", "PMID" : "24262291", "abstract" : "OBJECTIVE: Increased DNA methylation of the metabolic regulator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) has been reported in skeletal muscle from type 2 diabetes (T2D) subjects and from low birth weight (LBW) subjects with an increased risk of T2D. High-fat overfeeding increases PPARGC1A DNA methylation in muscle in a birth weight dependent manner. However, PPARGC1A DNA methylation in subcutaneous adipose tissue (SAT) in LBW subjects has not previously been investigated. Our objective was to determine PPARGC1A DNA methylation and mRNA expression in basal and insulin-stimulated SAT from LBW and matched normal birth weight (NBW) subjects during control and high-fat overfeeding.\n\nMATERIALS/METHODS: Nineteen young healthy men with LBW and 26 NBW controls were studied after both a 5-day high-fat overfeeding and a control diet in a randomized crossover setting. DNA methylation was assessed with bisulfite sequencing and mRNA expression with quantitative real-time PCR.\n\nRESULTS: Following high-fat overfeeding, increased SAT PPARGC1A DNA methylation was observed in LBW subjects but not in NBW controls. Basal SAT PPARGC1A mRNA expression was unaffected by diet and similar in the two groups. However, LBW subjects showed an increased SAT PPARGC1A mRNA expression during insulin-stimulation. SAT PPARGC1A methylation correlated inversely with mRNA expression during insulin-stimulation.\n\nCONCLUSIONS: The study adds to the increasing awareness of PPARGC1A DNA methylation being flexible and influenced by high-fat overfeeding in a birth weight dependent manner with muscle and fat responding differently. Further data are needed to understand the role of PPARGC1A DNA methylation in insulin resistance and developmental programming of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Gillberg", "given" : "Linn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobsen", "given" : "Stine C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00f6nn", "given" : "Tina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Br\u00f8ns", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaag", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2", "2" ] ] }, "language" : "English", "page" : "263-71", "publisher" : "Elsevier", "title" : "PPARGC1A DNA methylation in subcutaneous adipose tissue in low birth weight subjects--impact of 5 days of high-fat overfeeding.", "type" : "article-journal", "volume" : "63" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1371/journal.pone.0025254", "ISSN" : "1932-6203", "PMID" : "21980406", "abstract" : "Low birthweight, premature birth, intrauterine growth retardation, and maternal malnutrition have been related to an increased risk of cardiovascular disease, type 2 diabetes mellitus, obesity, and neuropsychiatric disorders later in life. Conversely, high birthweight has been linked to future risk of cancer. Global DNA methylation estimated by the methylation of repetitive sequences in the genome is an indicator of susceptibility to chronic diseases. We used data and biospecimens from an epigenetic birth cohort to explore the association between trajectories of fetal and maternal weight and LINE-1 methylation in 319 mother-child dyads. Newborns with low or high birthweight had significantly lower LINE-1 methylation levels in their cord blood compared to normal weight infants after adjusting for gestational age, sex of the child, maternal age at delivery, and maternal smoking during pregnancy (p\u200a=\u200a0.007 and p\u200a=\u200a0.036, respectively), but the magnitude of the difference was small. Infants born prematurely also had lower LINE-1 methylation levels in cord blood compared to term infants, and this difference, though small, was statistically significant (p\u200a=\u200a0.004). We did not find important associations between maternal prepregnancy BMI or gestational weight gain and global methylation of the cord blood or fetal placental tissue. In conclusion, we found significant differences in cord blood LINE-1 methylation among newborns with low and high birthweight as well as among prematurely born infants. Future studies may elucidate whether chromosomal instabilities or other functional consequences of these changes contribute to the increased risk of chronic diseases among individuals with these characteristics.", "author" : [ { "dropping-particle" : "", "family" : "Michels", "given" : "Karin B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Holly R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barault", "given" : "Ludovic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-4", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1", "28" ] ] }, "page" : "e25254", "title" : "Birthweight, maternal weight trajectories and global DNA methylation of LINE-1 repetitive elements.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0168-8227", "PMID" : "11137183", "abstract" : "The purpose of this study was to compare the prevalence of diabetes and risk factors for the disease in three ethnic groups in Taiwan; the Hakaas, Fukienese, and aborigines. A cross-sectional study of men and women aged 50-79 years were invited to attend a standardized interview and physical examination. Diabetes mellitus was defined as a fasting plasma glucose (concentration of greater than or = 126) or a previous diagnosis of diabetes. Demographic, socioeconomic, and risk factor data were obtained. A total of 1293 persons (468 Hakaas, 440 Fukienese, and 385 aborigines) completed the examination. Hakaas had the highest age-adjusted prevalence of diabetes, 17.9% in men and 15.5% in women, followed by Fukienese, 14.5% in men and 12.8% in women. Aborigines had a prevalence of 10.0% in men and 13.3% in women. Diabetes prevalence was positively associated with family history of diabetes, obesity, hypertension, and hypertriglyceridemia. The ethnic variation in diabetes prevalence was reduced after adjustment for age, sex and significant factors. The multivariate-adjusted odds ratios (95% confidence interval) were 1.27 (0.76-2.12) for Fukienese and 1.44 (0.89-2.33) for Hakaas compared with aborigines. Diabetes mellitus is a major public health problem in Taiwan and warrants prevention efforts tailored to the country's different ethnic groups.", "author" : [ { "dropping-particle" : "", "family" : "Chen", "given" : "K T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "C J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregg", "given" : "E W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engelgau", "given" : "M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narayan", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes research and clinical practice", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2001", "1" ] ] }, "page" : "59-66", "title" : "Prevalence of type 2 diabetes mellitus in Taiwan: ethnic variation and risk factors.", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1093/hmg/ddv119", "ISSN" : "1460-2083", "PMID" : "25869828", "abstract" : "Gestational age (GA) and birth weight have been implicated in the determination of long-term health. It has been hypothesized that changes in DNA methylation may mediate these long-term effects. We obtained DNA methylation profiles from cord blood and peripheral blood at ages 7 and 17 in the same children from the Avon Longitudinal Study of Parents and Children. Repeated-measures data were used to investigate changes in birth-related methylation during childhood and adolescence. Ten developmental phenotypes (e.g. height) were analysed to identify possible mediation of health effects by DNA methylation. In cord blood, methylation at 224 CpG sites was found to be associated with GA and 23 CpG sites with birth weight. Methylation changed in the majority of these sites over time, but neither birth characteristic was strongly associated with methylation at age 7 or 17 (using a conservative correction for multiple testing of P < 1.03 \u00d7 10(-7)), suggesting resolution of differential methylation by early childhood. Associations were observed between birth weight-associated CpG sites and phenotypic characteristics in childhood. One strong association involved birth weight, methylation of a CpG site proximal to the NFIX locus and bone mineral density at age 17. Analysis of serial methylation from birth to adolescence provided evidence for a lack of persistence of methylation differences beyond early childhood. Sites associated with birth weight were linked to developmental genes and have methylation levels which are associated with developmental phenotypes. Replication and interrogation of causal relationships are needed to substantiate whether methylation differences at birth influence the association between birth weight and development.", "author" : [ { "dropping-particle" : "", "family" : "Simpkin", "given" : "Andrew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suderman", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaunt", "given" : "Tom R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyttleton", "given" : "Oliver", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McArdle", "given" : "Wendy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "Susan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tilling", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davey Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Relton", "given" : "Caroline L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Human molecular genetics", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "2015", "4", "13" ] ] }, "page" : "ddv119-", "title" : "Longitudinal analysis of DNA methylation associated with birth weight and gestational age.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "193\u2013198", "plainTextFormattedCitation" : "193\u2013198", "previouslyFormattedCitation" : "193\u2013198" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }193–198 and ethnic variation in these profilesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s13148-015-0080-6", "ISSN" : "1868-7075", "abstract" : "The birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities. The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race and birth weight. Data was collected on a cohort of 87 live born infants. IGF1 methylation was measured in DNA isolated from the mononuclear fraction of umbilical cord blood collected after delivery. Quantitative, loci-specific methylation was assessed using the Infinium HumanMethylation27 BeadArray (Illumina Inc., San Diego, CA). Locus specific methylation of the IGF1 CpG site was validated on a subset of the original sample (N\u2009=\u200961) using pyrosequencing. Multiple linear regression was used to examine relationships between IGF1 methylation, race, and birth weight. A formal mediation analysis was then used to estimate the relationship of IGF1 methylation to race and birth weight.", "author" : [ { "dropping-particle" : "", "family" : "Straughen", "given" : "Jennifer K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sipahi", "given" : "Levent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uddin", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Misra", "given" : "Dawn P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Misra", "given" : "Vinod K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Epigenetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2015", "4", "21" ] ] }, "language" : "en", "page" : "47", "publisher" : "BioMed Central Ltd", "title" : "Racial differences in IGF1 methylation and birth weight", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "177", "plainTextFormattedCitation" : "177", "previouslyFormattedCitation" : "177" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }177, we are the first to undertake a large-scale comparison of differentially methylated regions for birth weight between South Asians infants and Caucasians.4.4.1 Ethnic heterogeneity in methylation at known birth weight genesBirth weight is a polygenic trait, influenced by multiple factors including genetic, constitutional, and environmental (e.g. in-utero) exposures. These include gestational age, infant sex, parental height, maternal risk factors such as pre-pregnancy weight, nutrition, hypertension, gestational diabetes and exposure to smoking during pregnancy, among others. In our analysis, percent methylation at all seven sites (from our primary analysis) explained 3.2% of the variation in birth weight in white Caucasians after considering a multivariate model including infant’s gestational age, sex, mothers pre-pregnancy BMI, smoking exposure, gestational diabetes and hypertension in pregnancy (Supplementary Table 4.12).Among the sites showing significant heterogeneity by ethnicity were probe sites on two genes associated with diabetes among other phenotypes, TCF7L2 and CDKAL1. Methylation at these CpG sites influence birth weight in white Caucasians, but this was not observed in South Asians. Association for TCF7L2 persisted after adjustment for gestational age, sex, and genotype at near-by SNP. TCF7L2 is a transcription factor involved in the Wnt signaling pathway. The rs7903146 SNP in the TCF7L2 gene is the hallmark type 2 diabetes variant. Functional studies and animal models suggest that TCF7L2 is involved in distribution of voltage-gated Ca2+ channelsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-0099", "ISSN" : "1939-327X", "PMID" : "19336690", "author" : [ { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rorsman", "given" : "Patrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "800-2", "title" : "Type 2 diabetes susceptibility gene TCF7L2 and its role in beta-cell function.", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "199", "plainTextFormattedCitation" : "199", "previouslyFormattedCitation" : "199" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }199, which in turn affect exocytosis of insulin from pancreatic beta-cellsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db08-1187", "ISSN" : "1939-327X", "PMID" : "19168596", "abstract" : "OBJECTIVE: Polymorphisms in the human TCF7L2 gene are associated with reduced insulin secretion and an increased risk of type 2 diabetes. However, the mechanisms by which TCF7L2 affect insulin secretion are still unclear. We define the effects of TCF7L2 expression level on mature beta-cell function and suggest a potential mechanism for its actions.\n\nRESEARCH DESIGN AND METHODS: TCF7L2 expression in rodent islets and beta-cell lines was altered using RNAi or adenoviral transduction. Beta-cell gene profiles were measured by quantitative real-time PCR and the effects on intracellular signaling and exocytosis by live cell imaging, electron microscopy, and patch clamp electrophysiology.\n\nRESULTS: Reducing TCF7L2 expression levels by RNAi decreased glucose- but not KCl-induced insulin secretion. The glucose-induced increments in both ATP/ADP ratio and cytosolic free Ca2+ concentration ([Ca2+]i) were increased compared with controls. Overexpression of TCF7L2 exerted minor inhibitory effects on glucose-regulated changes in [Ca2+]i and insulin release. Gene expression profiling in TCF7L2-silenced cells revealed increased levels of mRNA encoding syntaxin 1A but decreased Munc18-1 and ZnT8 mRNA. Whereas the number of morphologically docked vesicles was unchanged by TCF7L2 suppression, secretory granule movement increased and capacitance changes decreased, indicative of defective vesicle fusion.\n\nCONCLUSION: TCF7L2 is involved in maintaining expression of beta-cell genes regulating secretory granule fusion. Defective insulin exocytosis may thus underlie increased diabetes incidence in carriers of the at-risk TCF7L2 alleles.", "author" : [ { "dropping-particle" : "", "family" : "Silva Xavier", "given" : "Gabriela", "non-dropping-particle" : "da", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loder", "given" : "Merewyn K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McDonald", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tarasov", "given" : "Andrei I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carzaniga", "given" : "Raffaella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kronenberger", "given" : "Katrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barg", "given" : "Sebastian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rutter", "given" : "Guy A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "894-905", "title" : "TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells.", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "200", "plainTextFormattedCitation" : "200", "previouslyFormattedCitation" : "200" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }200. Similarly, while the specific function of CDKAL1, a member of a methylthiotransferase family, is not known, it too is implicated in insulin secretionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-008-1083-z", "ISSN" : "0012-186X", "PMID" : "18618095", "abstract" : "AIMS/HYPOTHESIS: Genome-wide association studies have recently identified novel type 2 diabetes susceptibility gene regions. We assessed the effects of six of these regions on insulin secretion as determined by a hyperglycaemic clamp.\n\nMETHODS: Variants of the HHEX/IDE, CDKAL1, SLC30A8, IGF2BP2 and CDKN2A/CDKN2B genes were genotyped in a cohort of 146 participants with NGT and 126 with IGT from the Netherlands and Germany, who all underwent a hyperglycaemic clamp at 10 mmol/l glucose.\n\nRESULTS: Variants of CDKAL1 and IGF2BP2 were associated with reductions in first-phase insulin secretion (34% and 28%, respectively). The disposition index was also significantly reduced. For gene regions near HHEX/IDE, SLC30A8 and CDKN2A/CDKN2B we did not find significant associations with first-phase insulin secretion (7-18% difference between genotypes; all p > 0.3). None of the variants showed a significant effect on second-phase insulin secretion in our cohorts (2-8% difference between genotypes, all p > 0.3). Furthermore, the gene variants were not associated with the insulin sensitivity index.\n\nCONCLUSIONS: Variants of CDKAL1 and IGF2BP2 attenuate the first phase of glucose-stimulated insulin secretion but show no effect on the second phase of insulin secretion. Our results, based on hyperglycaemic clamps, provide further insight into the pathogenic mechanism behind the association of these gene variants with type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Groenewoud", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dekker", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fritsche", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reiling", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nijpels", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heine", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maassen", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Machicao", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sch\u00e4fer", "given" : "S A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00e4ring", "given" : "H U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "'t Hart", "given" : "L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haeften", "given" : "T W", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "page" : "1659-63", "title" : "Variants of CDKAL1 and IGF2BP2 affect first-phase insulin secretion during hyperglycaemic clamps.", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0015553", "ISSN" : "1932-6203", "PMID" : "21151568", "abstract" : "BACKGROUND: A variant of the CDKAL1 gene was reported to be associated with type 2 diabetes and reduced insulin release in humans; however, the role of CDKAL1 in \u03b2 cells is largely unknown. Therefore, to determine the role of CDKAL1 in insulin release from \u03b2 cells, we studied insulin release profiles in CDKAL1 gene knockout (CDKAL1 KO) mice.\n\nPRINCIPAL FINDINGS: Total internal reflection fluorescence imaging of CDKAL1 KO \u03b2 cells showed that the number of fusion events during first-phase insulin release was reduced. However, there was no significant difference in the number of fusion events during second-phase release or high K(+)-induced release between WT and KO cells. CDKAL1 deletion resulted in a delayed and slow increase in cytosolic free Ca(2+) concentration during high glucose stimulation. Patch-clamp experiments revealed that the responsiveness of ATP-sensitive K(+) (K(ATP)) channels to glucose was blunted in KO cells. In addition, glucose-induced ATP generation was impaired. Although CDKAL1 is homologous to cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1, there was no difference in the kinase activity of CDK5 between WT and CDKAL1 KO islets.\n\nCONCLUSIONS/SIGNIFICANCE: We provide the first report describing the function of CDKAL1 in \u03b2 cells. Our results indicate that CDKAL1 controls first-phase insulin exocytosis in \u03b2 cells by facilitating ATP generation, K(ATP) channel responsiveness and the subsequent activity of Ca(2+) channels through pathways other than CDK5-mediated regulation.", "author" : [ { "dropping-particle" : "", "family" : "Ohara-Imaizumi", "given" : "Mica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshida", "given" : "Masashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aoyagi", "given" : "Kyota", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saito", "given" : "Taro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamura", "given" : "Tadashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takenaka", "given" : "Hitoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akimoto", "given" : "Yoshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamichi", "given" : "Yoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takanashi-Yanobu", "given" : "Rieko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nishiwaki", "given" : "Chiyono", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawakami", "given" : "Hayato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hisanaga", "given" : "Shin-ichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kakei", "given" : "Masafumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagamatsu", "given" : "Shinya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-2", "issue" : "12", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "e15553", "title" : "Deletion of CDKAL1 affects mitochondrial ATP generation and first-phase insulin exocytosis.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/ng2043", "ISSN" : "1061-4036", "PMID" : "17460697", "abstract" : "We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.", "author" : [ { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reynisdottir", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsdottir", "given" : "Thorbjorg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Styrkarsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gretarsdottir", "given" : "Solveig", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Shyamali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Adam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Snorradottir", "given" : "Steinunn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjarnason", "given" : "Hjordis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Maggie C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bagger", "given" : "Yu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilensky", "given" : "Robert L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reilly", "given" : "Muredach P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adeyemo", "given" : "Adebowale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuanxiu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhou", "given" : "Jie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudnason", "given" : "Vilmundur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Guanjie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Hanxia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lashley", "given" : "Kerrie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doumatey", "given" : "Ayo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "So", "given" : "Wing-Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ma", "given" : "Ronald C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jorgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Vliet-Ostaptchouk", "given" : "Jana", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofker", "given" : "Marten H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Christiansen", "given" : "Claus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotimi", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gurney", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "Juliana C N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurdsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gulcher", "given" : "Jeffrey R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "2007", "6" ] ] }, "page" : "770-5", "title" : "A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "201\u2013203", "plainTextFormattedCitation" : "201\u2013203", "previouslyFormattedCitation" : "201\u2013203" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }201–203. Both these genes may affect birth weight via in-utero reduction of insulin secretion and consequent impaired insulin-mediated fetus growth, as suggested by the fetal insulin hypothesisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9378", "PMID" : "2658601", "abstract" : "Plasma insulin and blood glucose levels were measured in umbilical venous samples obtained by cordocentesis from 42 small-for-gestational-age and 68 appropriate-for-gestational-age fetuses at 17 to 38 weeks' gestation. In the appropriate-for-gestational-age fetuses plasma insulin and the insulin/glucose ratio increased exponentially with gestation, reflecting the progressive maturation of the pancreas. Maternal blood glucose concentration, not fetal plasma insulin, was the major determinant of fetal blood glucose concentration. In some small-for-gestational-age fetuses hypoinsulinemia and hypoglycemia were found; the two were significantly correlated. However, the fetal insulin/glucose ratio was lower in small-for-gestational-age fetuses than in appropriate-for-gestational-age ones, suggesting that hypoinsulinemia in a small-for-gestational-age fetuses is not only the result of hypoglycemia but also a consequence of pancreatic dysfunction. The degree of fetal smallness did not correlate with plasma insulin or with the insulin/glucose ratio. These findings suggest that insulin may influence fetal growth through its action on nutrient uptake and utilization but it is not the primary determinant of fetal size.", "author" : [ { "dropping-particle" : "", "family" : "Economides", "given" : "D L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proudler", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nicolaides", "given" : "K H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of obstetrics and gynecology", "id" : "ITEM-1", "issue" : "5 Pt 1", "issued" : { "date-parts" : [ [ "1989", "5" ] ] }, "page" : "1091-4", "title" : "Plasma insulin in appropriate- and small-for-gestational-age fetuses.", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/jech.58.2.126", "ISSN" : "0143-005X", "author" : [ { "dropping-particle" : "", "family" : "Davey Smith", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Epidemiology & Community Health", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2004", "2", "1" ] ] }, "page" : "126-128", "title" : "Birth characteristics of offspring and parental diabetes: evidence for the fetal insulin hypothesis", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "204,205", "plainTextFormattedCitation" : "204,205", "previouslyFormattedCitation" : "204,205" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }204,205.Furthermore, methylation of probe sites on IGF1, HMGA2 and CALCR were also associated with birth weight in Caucasians, but not South Asians. HMGA2 encodes proteins that belong to the non-histone chromosomal high-mobility group. Functional, knockout, and amplification studies suggest a role of these proteins in adipogenesis and mesenchymal differentiation. Subsequently, at a genome-wide level, this gene is robustly associated with various dimensions of growth, including height, infant head circumference, and tooth development. Studies of HMGA2 elucidating its role in adipocyteADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/oby.20137", "ISSN" : "1930-739X", "PMID" : "24106133", "abstract" : "OBJECTIVE: In this study the activation of HMGA2 and overexpression by FGF1-driven stimulation of adipose tissue derived stem cells (ADSCs) in adipose tissue tumors were analyzed. In addition, the expression of HMGA2 and PPAR-gamma mRNA were quantified in canine subcutaneous abdominal adipose tissue from normal and overweight purebred dogs.\n\nDESIGN AND METHODS: ADSCs and adipose tissue explants stimulated with FGF1 followed by gene expression analyses of HMGA2 and p14(Arf) using Western-blot and qRT-PCR. Furthermore, canine subcutaneous white adipose tissue (WAT) were analyzed by qRT-PCR for their expression of HMGA2 and PPAR-gamma.\n\nRESULTS: ADSCs and adipose tissue explants are able to execute a HMGA2 response upon FGF1 stimulation. FGF1 enhances proliferation of ADSCs by a HMGA2-dependent mechanism. In lipomas increase of HMGA2 is accompanied by increased expression of p14(Arf) . Furthermore, a significantly elevated level of HMGA2 in overweight dogs and a negative correlation between the expression of HMGA2 and PPAR-gamma in subcutaneous cWAT were noted.\n\nCONCLUSIONS: These results suggest that WAT contains cells that as essential part of adipogenesis up-regulate HMGA2 resulting from growth factor stimulation. In subgroups of lipoma, constitutive activation of HMGA2 due to rearrangements replaces the temporal response triggered by growth factors.", "author" : [ { "dropping-particle" : "", "family" : "Thies", "given" : "Helge W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nolte", "given" : "Ingo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wenk", "given" : "Heiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mertens", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bullerdiek", "given" : "J\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Markowski", "given" : "Dominique N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity (Silver Spring, Md.)", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "141-50", "title" : "Permanent activation of HMGA2 in lipomas mimics its temporal physiological activation linked to the gain of adipose tissue.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "206", "plainTextFormattedCitation" : "206", "previouslyFormattedCitation" : "206" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }206 and muscle development and proliferationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.devcel.2012.10.019", "ISSN" : "1878-1551", "PMID" : "23177649", "abstract" : "A group of genes that are highly and specifically expressed in proliferating skeletal myoblasts during myogenesis was identified. Expression of one of these genes, Hmga2, increases coincident with satellite cell activation, and later its expression significantly declines correlating with fusion of myoblasts into myotubes. Hmga2 knockout mice exhibit impaired muscle development and reduced myoblast proliferation, while overexpression of HMGA2 promotes myoblast growth. This perturbation in proliferation can be explained by the finding that HMGA2 directly regulates the RNA-binding protein IGF2BP2. Add-back of IGF2BP2 rescues the phenotype. IGF2BP2 in turn binds to and controls the translation of a set of mRNAs, including c-myc, Sp1, and Igf1r. These data demonstrate that the HMGA2-IGF2BP2 axis functions as a key regulator of satellite cell activation and therefore skeletal muscle development.", "author" : [ { "dropping-particle" : "", "family" : "Li", "given" : "Zhizhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilbert", "given" : "Jason A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Yunyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Minsi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qiu", "given" : "Qiong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramanujan", "given" : "Krishnan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shavlakadze", "given" : "Tea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eash", "given" : "John K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaramozza", "given" : "Annarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goddeeris", "given" : "Matthew M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirsch", "given" : "David G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Kevin P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brack", "given" : "Andrew S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glass", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Developmental cell", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "12", "11" ] ] }, "page" : "1176-88", "title" : "An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis.", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "207", "plainTextFormattedCitation" : "207", "previouslyFormattedCitation" : "207" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }207 makes this gene an obvious candidate for implication in birth weight. CALCR codes a G-coupled receptor that binds calcitonin and is important in maintaining calcium homeostasis. Although its specific role in birth weight is not clear, it is known to interact with LRP1ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1083/jcb.200302069", "ISSN" : "0021-9525", "PMID" : "12821648", "abstract" : "Thrombospondin (TSP) signals focal adhesion disassembly (the intermediate adhesive state) through interactions with cell surface calreticulin (CRT). TSP or a peptide (hep I) of the active site induces focal adhesion disassembly through binding to CRT, which activates phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinase (ERK) through Galphai2 proteins. Because CRT is not a transmembrane protein, it is likely that CRT signals as part of a coreceptor complex. We now show that low density lipoprotein receptor-related protein (LRP) mediates focal adhesion disassembly initiated by TSP binding to CRT. LRP antagonists (antibodies, receptor-associated protein) block hep I/TSP-induced focal adhesion disassembly. LRP is necessary for TSP/hep I signaling because TSP/hep I is unable to stimulate focal adhesion disassembly or ERK or PI3K signaling in fibroblasts deficient in LRP. LRP is important in TSP-CRT signaling, as shown by the ability of hep I to stimulate association of Galphai2 with LRP. The isolated proteins LRP and CRT interact, and LRP and CRT are associated with hep I in molecular complexes extracted from cells. These data establish a mechanism of cell surface CRT signaling through its coreceptor, LRP, and suggest a novel function for LRP in regulating cell adhesion.", "author" : [ { "dropping-particle" : "", "family" : "Orr", "given" : "Anthony Wayne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedraza", "given" : "Claudio E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pallero", "given" : "Manuel Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elzie", "given" : "Carrie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goicoechea", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strickland", "given" : "Dudley K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murphy-Ullrich", "given" : "Joanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of cell biology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2003", "6", "23" ] ] }, "page" : "1179-89", "title" : "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly.", "type" : "article-journal", "volume" : "161" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "208", "plainTextFormattedCitation" : "208", "previouslyFormattedCitation" : "208" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }208, involved in energy homeostasisADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1152/physrev.00033.2007", "ISSN" : "0031-9333", "PMID" : "18626063", "abstract" : "The LDL receptor-related protein (originally called LRP, but now referred to as LRP1) is a large endocytic receptor that is widely expressed in several tissues. LRP1 is a member of the LDL receptor family that plays diverse roles in various biological processes including lipoprotein metabolism, degradation of proteases, activation of lysosomal enzymes, and cellular entry of bacterial toxins and viruses. Deletion of the LRP1 gene leads to lethality in mice, revealing a critical, but as of yet, undefined role in development. Tissue-specific gene deletion studies reveal an important contribution of LRP1 in the vasculature, central nervous system, macrophages, and adipocytes. Three important properties of LRP1 dictate its diverse role in physiology: 1) its ability to recognize more than 30 distinct ligands, 2) its ability to bind a large number of cytoplasmic adaptor proteins via determinants located on its cytoplasmic domain in a phosphorylation-specific manner, and 3) its ability to associate with and modulate the activity of other transmembrane receptors such as integrins and receptor tyrosine kinases.", "author" : [ { "dropping-particle" : "", "family" : "Lillis", "given" : "Anna P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duyn", "given" : "Lauren B", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murphy-Ullrich", "given" : "Joanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strickland", "given" : "Dudley K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiological reviews", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008", "7" ] ] }, "page" : "887-918", "title" : "LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pbio.1000575", "ISSN" : "1545-7885", "PMID" : "21264353", "abstract" : "Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Qiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zerbinatti", "given" : "Celina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhan", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolber", "given" : "Benedict J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herz", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muglia", "given" : "Louis J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bu", "given" : "Guojun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS biology", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "11" ] ] }, "page" : "e1000575", "title" : "Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "209,210", "plainTextFormattedCitation" : "209,210", "previouslyFormattedCitation" : "209,210" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }209,210. Lastly, IGF1 encodes a protein, similar to insulin in structure and function, which plays an integral role in mediating growth and development. In adults, SNPs on IGF1 are associated with height at a genome-wide levelADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/hmg/ddq091", "ISSN" : "1460-2083", "PMID" : "20189936", "abstract" : "Previous genome-wide association studies (GWASs) have identified several loci associated with human height; however, such evidence was mostly reported in Caucasian populations. Since the different distributions of height between populations suggest their different genetic backgrounds, analysis in different populations would be useful. Here, we present the results of a GWAS for adult height in 19 633 Japanese subjects. We found eight significantly associated loci that satisfied the genome-wide significance level (P < 5.0 x 10(-8)). Of these, the association to the LHX3-QSOX2 locus was entirely novel (rs12338076, P = 2.2 x 10(-8)). We also identified the association to the IGF1 locus (rs17032362, P = 8.1 x 10(-9)). Conditional association analysis in the IGF1 locus with rs17032362 suggested the existence of an additional independent association with height to this locus (rs1457595, P = 1.2 x 10(-5)). We observed large differences in the allele frequencies of rs17032362 and rs1457595 between Japanese (34 and 9%, respectively) and Caucasian (1.7 and 0%, respectively) populations, thereby suggesting weak statistical powers for the IGF1 locus in the previous Caucasian GWASs for height. We extensively compared our results with those of previous reports on the Caucasian and Korean populations. We were able to replicate all four loci previously reported in Koreans (EFEMP1, ZBTB38, HMGA1 and PLAG1, P < 5.0 x 10(-8)) and 15 loci identified in Caucasians (P < 0.001). The combination of the height-associated loci identified in our study and the previous GWASs demonstrated an effect size of 1.26 cm (95% confidence interval: 1.18-1.34) per 1.0 increase of the normalized Z score for height-increasing alleles, explaining 4.6% of the total variance of adult height.", "author" : [ { "dropping-particle" : "", "family" : "Okada", "given" : "Yukinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamatani", "given" : "Yoichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takahashi", "given" : "Atsushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matsuda", "given" : "Koichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hosono", "given" : "Naoya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohmiya", "given" : "Hiroko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daigo", "given" : "Yataro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Kazuhiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kubo", "given" : "Michiaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Yusuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamatani", "given" : "Naoyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Human molecular genetics", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "6", "1" ] ] }, "page" : "2303-12", "title" : "A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "211", "plainTextFormattedCitation" : "211", "previouslyFormattedCitation" : "211" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }211. Thus, involvement of a CpG site on this gene in birth weight is unsurprising. Notably, SNPs on IGF1 have also been associated with fasting glucose and insulin in adultsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2274", "ISSN" : "1546-1718", "PMID" : "22581228", "abstract" : "Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and \u03b2-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 \u00d7 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.", "author" : [ { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hivert", "given" : "Marie-France", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grimsby", "given" : "Jonna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bielak", "given" : "Lawrence F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amin", "given" : "Najaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnes", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cadby", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ladenvall", "given" : "Claes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lahti", "given" : "Jari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yongmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martinez-Larrad", "given" : "Maria Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montasser", "given" : "May E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasmussen-Torvik", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salo", "given" : "Perttu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sattar", "given" : "Naveed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shungin", "given" : "Dmitry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrade", "given" : "Mariza", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andrews", "given" : "Jeanette S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aspelund", "given" : "Thor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandinelli", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beckmann", "given" : "Jacques S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellis", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blangero", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boban", "given" : "Mladen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouchard", "given" : "Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budimir", "given" : "Danijela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlson", "given" : "Olga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corbat\u00f3n-Anchuelo", "given" : "Arturo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitriou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eiriksdottir", "given" : "Gudny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eury", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ford", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudnason", "given" : "Vilmundur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansson", "given" : "Ola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Tamara B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jhun", "given" : "Min A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Paul C D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jukema", "given" : "J Wouter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kardia", "given" : "Sharon L R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolcic", "given" : "Ivana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lannfelt", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launer", "given" : "Lenore J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leander", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Guo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindstrom", "given" : "Jaana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miljkovic", "given" : "Iva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeff", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Ken K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palotie", "given" : "Aarno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pehlic", "given" : "Marina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pericic", "given" : "Marijana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perusse", "given" : "Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peyser", "given" : "Patricia A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00e4ikk\u00f6nen", "given" : "Katri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sabater-Lleal", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Savage", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-Rios", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smit", "given" : "Johannes H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Albert Vernon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stan\u010d\u00e1kov\u00e1", "given" : "Alena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Sun", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trompet", "given" : "Stella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uusitupa", "given" : "Matti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vikstr\u00f6m", "given" : "Max", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vohl", "given" : "Marie-Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "Gerard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Widen", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willems", "given" : "Sara M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jacqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yaghootkar", "given" : "Hanieh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zemunik", "given" : "Tatijana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zgaga", "given" : "Lina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "7" ] ] }, "page" : "659-69", "title" : "A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.520", "ISSN" : "1546-1718", "PMID" : "20081858", "abstract" : "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henneman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dehghan", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lajunen", "given" : "Taina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabena", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sethupathy", "given" : "Praveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariyurek", "given" : "Yavuz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barter", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochud", "given" : "Murielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crisponi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Ian N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fedson", "given" : "Annette C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Rosinsky", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frants", "given" : "Rune", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwilliam", "given" : "Rhian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xijing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hillman", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesaniemi", "given" : "Y Antero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskinen", "given" : "Seppo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahley", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Larrad", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukherjee", "given" : "Sutapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naitza", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00f9", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paolisso", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattaro", "given" : "Cristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Andreas F H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posthuma", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolandsson", "given" : "Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurethsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Laila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijk", "given" : "Ko Willems", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visvikis-Siest", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogelzangs", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "Kim L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jaqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnell", "given" : "John W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zethelius", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spranger", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-R\u00edos", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "105-16", "title" : "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "9,212", "plainTextFormattedCitation" : "9,212", "previouslyFormattedCitation" : "9,212" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }9,212.The fact that there is ethnic variation in the methylation of these seven CpG sites may be suggestive of the multitude of pathways for modulating weight and their relative importance in different ethnic groups. It is possible that while pathways involving TCF7L2, CDKAL1, CALCR, IGF1, and HMGA2 are important in governing birth weight for white Caucasians, they may be less marked in South Asians as a result of differential selection / in-utero environmental pressuresADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1503/cmaj.050649", "ISSN" : "1488-2329", "PMID" : "16389231", "author" : [ { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waltman", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006", "1", "3" ] ] }, "page" : "25-6", "title" : "Why don't pigs get diabetes? Explanations for variations in diabetes susceptibility in human populations living in a diabetogenic environment.", "type" : "article-journal", "volume" : "174" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1101/gr.171439.113", "ISSN" : "1549-5469", "PMID" : "24709820", "abstract" : "Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment. Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, interindividual variation in methylation can also be a consequence of DNA sequence polymorphisms that result in methylation quantitative trait loci (methQTLs) and, potentially, the interaction between fixed genetic variation and environmental influences. We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. MethQTLs were readily detected in neonatal methylomes, and genotype alone best explained \u223c25% of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age, and birth order. Our study sheds new light on the complex relationship between biological inheritance as represented by genotype and individual prenatal experience and suggests the importance of considering both fixed genetic variation and environmental factors in interpreting epigenetic variation.", "author" : [ { "dropping-particle" : "", "family" : "Teh", "given" : "Ai Ling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pan", "given" : "Hong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Mei-Lyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dogra", "given" : "Shaillay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Johnny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "MacIsaac", "given" : "Julia L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mah", "given" : "Sarah M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McEwen", "given" : "Lisa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saw", "given" : "Seang-Mei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godfrey", "given" : "Keith M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chong", "given" : "Yap-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwek", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwoh", "given" : "Chee-Keong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soh", "given" : "Shu-E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chong", "given" : "Mary F F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barton", "given" : "Sheila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karnani", "given" : "Neerja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheong", "given" : "Clara Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buschdorf", "given" : "Jan Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "St\u00fcnkel", "given" : "Walter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kobor", "given" : "Michael S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meaney", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluckman", "given" : "Peter D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holbrook", "given" : "Joanna D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genome research", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2014", "7", "7" ] ] }, "page" : "1064-74", "title" : "The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "61,213", "plainTextFormattedCitation" : "61,213", "previouslyFormattedCitation" : "61,213" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }61,213. This is supported by a lack of association for the above-described CpG sites in South Asians, but a very robust one in white Caucasians. In fact, in addition to methylation levels, the SNPs themselves appear to be more strongly associated with birth weight in white Caucasians. When we tested the association of a genotype score of the 9 birth weight SNPs available in both South Asian and white Caucasians, we found that the score significantly predicted a decrease in birth weight for each risk allele among Caucasians (β-coefficient=-0.042, P=1.36x10-2), but was not associated with birth weight in South Asians (β-coefficient= -0.021, P=2.05x10-1) (Supplementary Table 4.5). Our methylation analysis revealed that in addition to a variation in strength of association by ethnicity for the seven sites, the direction of association also varied. Specifically, an increase in methylation led to an increase in birth weight for South Asian newborns, but a decrease for white Caucasians. Though previous literature on ethnic variation in methylation is sparse, one study shows a similar observation. King et al. have also reported a variable direction of effect of CpG sites on IGF2, H19, MEG3, and NNAT with parameters of gestational growth depending on parental ethnicityADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/jech-2014-204781", "ISSN" : "1470-2738", "PMID" : "25678712", "abstract" : "BACKGROUND: Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood.\n\nMETHODS: We measured DNA methylation at DMRs regulating genomically imprinted domains (IGF2/H19, DLK1/MEG3, NNAT and PLAGL1) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010-2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences.\n\nRESULTS: Unadjusted race/ethnic differences only were evident for DMRs regulating MEG3 and IGF2; race/ethnic differences persisted in IGF2/H19 and NNAT after accounting for income and education.\n\nCONCLUSIONS: Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers.", "author" : [ { "dropping-particle" : "", "family" : "King", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murphy", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoyo", "given" : "Cathrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of epidemiology and community health", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "2", "12" ] ] }, "title" : "Epigenetic regulation of Newborns' imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "178", "plainTextFormattedCitation" : "178", "previouslyFormattedCitation" : "178" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }178. But, as a parental-effect is also considered, it is difficult to disentangle the role ethnicity plays in the direction of effect. This divergence in the direction of effect by ethnicity may explain the observed ethnic heterogeneity in birth weight, however studies of gene expression are needed to assess whether changes in methylation at these sites translate to changes in the expression of these genes and whether ethnic heterogeneity is present in the level of gene expression. 4.4.3 Regional analysis of significant sitesSince CpG sites often occur within clusters and CGIs which together control transcription and gene expressionADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/nar/gks928", "ISSN" : "1362-4962", "PMID" : "23066096", "abstract" : "Methylation of a CpG island is a faithful marker of silencing of its associated gene. Different approaches report the methylation status of a CpG island based on the determination of one or a few CpG sites by assuming the homogeneity of methylation along the element. This strategy is frequently applied in both locus-specific and genome-wide studies, but often without a validation of the representativeness of the interrogated CpG site compared with the whole element. We have evaluated the predictive informativeness of the HpaII sites located in CpG islands using data from high-resolution methylome maps, which offer the possibility to assess the methylation homogeneity of each CpG island and to determine the reporter accuracy of single sites as surrogate markers. An excellent correlation was observed between the HpaII and CpG island methylation levels (r > 0.93). At the qualitative level, the predictive sensitivity of HpaII was >95% with >92% specificity for methylated CpG islands and >90% sensitivity with >95% specificity for unmethylated CpG islands. This analysis provides a global validation framework for strategies based on the use of the methylation-sensitive HpaII restriction enzyme.", "author" : [ { "dropping-particle" : "", "family" : "Barrera", "given" : "V\u00edctor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peinado", "given" : "Miguel A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nucleic acids research", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2012", "12", "12" ] ] }, "page" : "11490-8", "title" : "Evaluation of single CpG sites as proxies of CpG island methylation states at the genome scale.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/bioinformatics/btt498", "ISSN" : "1367-4803", "PMID" : "23990415", "abstract" : "MOTIVATION: DNA methylation is a heritable modifiable chemical process that affects gene transcription and is associated with other molecular markers (e.g. gene expression) and biomarkers (e.g. cancer or other diseases). Current technology measures methylation in hundred of thousands, or millions of CpG sites throughout the genome. It is evident that neighboring CpG sites are often highly correlated with each other, and current literature suggests that clusters of adjacent CpG sites are co-regulated.\n\nRESULTS: We develop the Adjacent Site Clustering (A-clustering) algorithm to detect sets of neighboring CpG sites that are correlated with each other. To detect methylation regions associated with exposure, we propose an analysis pipeline for high-dimensional methylation data in which CpG sites within regions identified by A-clustering are modeled as multivariate responses to environmental exposure using a generalized estimating equation approach that assumes exposure equally affects all sites in the cluster. We develop a correlation preserving simulation scheme, and study the proposed methodology via simulations. We study the clusters detected by the algorithm on high dimensional dataset of peripheral blood methylation of pesticide applicators.\n\nAVAILABILITY: We provide the R package Aclust that efficiently implements the A-clustering and the analysis pipeline, and produces analysis reports. The package is found on \n\nCONTACT: tsofer@hsph.harvard.edu", "author" : [ { "dropping-particle" : "", "family" : "Sofer", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schifano", "given" : "E. D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoppin", "given" : "J. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hou", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baccarelli", "given" : "A. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Bioinformatics", "id" : "ITEM-2", "issue" : "22", "issued" : { "date-parts" : [ [ "2013", "8", "29" ] ] }, "page" : "2884-2891", "title" : "A-clustering: a novel method for the detection of co-regulated methylation regions, and regions associated with exposure", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "173,174", "plainTextFormattedCitation" : "173,174", "previouslyFormattedCitation" : "173,174" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }173,174, we investigated the presence of clusters around the seven sites that were significant in our primary analysis. If there was evidence of clusters, we estimated the effect of methylation at the entire element on birth weight. CpG sites on TCF7L2 and CALCR from our primary analysis appeared to be greatly correlated with neighboring sites. Average methylation over the entire element at TCF7L2 revealed a strengthened effect of methylation on birth weight, adjusted for gestational age, sex, and genotype, in white Caucasians. Conversely, averaging methylation at neighboring sites for cg23061150 on CALCR diminished the effect of methylation on birth weight. While correlated, neighboring sites for cg23061150 are likely not part of a CpG cluster as they span a region of 17,108 base pairs. Previous work in mammalian promoters has suggested that these sequences span between 300 and 3,000 base pairsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/nar/gni180", "ISSN" : "1362-4962", "PMID" : "16314307", "abstract" : "Promoters are molecular 'modules', which are controlled as individual entities yet are often analyzed by nuclease digestion methodologies which, a priori, destroy this modularity. About 40% of mammalian genes contain CpG islands in their promoters and exonic regions, which are normally unmethylated. We developed a footprinting strategy to map the chromatin structure at unmethylated CpG islands by treatment of isolated nuclei with the CpG-specific DNA methyltransferase SssI (M.SssI), followed by genomic bisulfite sequencing of individual progeny DNA molecules. This gave single molecule resolution over the promoter region and allowed for the physical linkage between binding sites on individual promoter molecules to be maintained. Comparison of the p16 promoters in two human cell lines, J82 and LD419, expressing the p16 gene at 25-fold different levels showed that the two cell lines contain remarkably different, heterogeneously positioned nucleosomes over the promoter region, which were not distinguishable by standard methods using nucleases. Our high resolution approach gives a 'digitized' visualization of each promoter providing information regarding nucleosome occupancy and may be utilized to define transcription factor binding and chromatin remodeling.", "author" : [ { "dropping-particle" : "", "family" : "Fatemi", "given" : "Mehrnaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pao", "given" : "Martha M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jeong", "given" : "Shinwu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gal-Yam", "given" : "Einav Nili", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egger", "given" : "Gerda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weisenberger", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Peter A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nucleic acids research", "id" : "ITEM-1", "issue" : "20", "issued" : { "date-parts" : [ [ "2005", "1", "27" ] ] }, "page" : "e176", "title" : "Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level.", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "214", "plainTextFormattedCitation" : "214", "previouslyFormattedCitation" : "214" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }214. Even the closest CpG probe site to cg23061150 constituted a distance of 6,772 base pairs. Therefore, it is either possible that the probe sites available for testing do not cover the region within 3,000 base pairs of cg23061150 or that it is not constituted within a CpG cluster.4.3.4 Genome-wide methylation for birth weight in South AsiansIt is important to note that GWA-studies identifying the SNPs/genes investigated in our analysis were mostly performed in white Caucasians. The fact that methylation at these genes was not robustly associated with birth weight in South Asians underscores the possibility that birth weight may be influenced by unique genes in this group. To address this current limitation of knowledge, we conducted a genome-wide search of CpG sites associated with birth weight in South Asians and found three sites possibly unique to this group. Importantly, these sites were not associated with the outcome in white Caucasians. As these sites show suggestive significance (P<10-5), we recommend further testing in a well-powered sample and independent replication if the sites reach genome-wide significance. The Q-Q plot provides evidence that there was likely no inflation of type 1 errorADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1002625", "ISSN" : "1553-7404", "PMID" : "22496670", "abstract" : "Recently, Wu and colleagues [1] proposed two novel statistics for genome-wide interaction analysis using case/control or case-only data. In computer simulations, their proposed case/control statistic outperformed competing approaches, including the fast-epistasis option in PLINK and logistic regression analysis under the correct model; however, reasons for its superior performance were not fully explored. Here we investigate the theoretical properties and performance of Wu et al.'s proposed statistics and explain why, in some circumstances, they outperform competing approaches. Unfortunately, we find minor errors in the formulae for their statistics, resulting in tests that have higher than nominal type 1 error. We also find minor errors in PLINK's fast-epistasis and case-only statistics, although theory and simulations suggest that these errors have only negligible effect on type 1 error. We propose adjusted versions of all four statistics that, both theoretically and in computer simulations, maintain correct type 1 error rates under the null hypothesis. We also investigate statistics based on correlation coefficients that maintain similar control of type 1 error. Although designed to test specifically for interaction, we show that some of these previously-proposed statistics can, in fact, be sensitive to main effects at one or both loci, particularly in the presence of linkage disequilibrium. We propose two new \"joint effects\" statistics that, provided the disease is rare, are sensitive only to genuine interaction effects. In computer simulations we find, in most situations considered, that highest power is achieved by analysis under the correct genetic model. Such an analysis is unachievable in practice, as we do not know this model. However, generally high power over a wide range of scenarios is exhibited by our joint effects and adjusted Wu statistics. We recommend use of these alternative or adjusted statistics and urge caution when using Wu et al.'s originally-proposed statistics, on account of the inflated error rate that can result.", "author" : [ { "dropping-particle" : "", "family" : "Ueki", "given" : "Masao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "1", "5" ] ] }, "page" : "e1002625", "publisher" : "Public Library of Science", "title" : "Improved statistics for genome-wide interaction analysis.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "215", "plainTextFormattedCitation" : "215", "previouslyFormattedCitation" : "215" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }215 (Figure 4.2).The importance of ethnic specific evaluation was recently highlighted by a whole genome sequencing experiment of 168 South Asians and whole-exome sequencing of 147 South Asians, which identified ethnic stratification in genes involved in energy conservation, including APOH, IGF1, IGF2, LYN, LDLR, NEUROD1, PNPLA2 and VLDLRADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0102645", "ISSN" : "1932-6203", "PMID" : "25115870", "abstract" : "The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.", "author" : [ { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turro", "given" : "Ernest", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "William R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "Sian-Tsung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afzal", "given" : "Uzma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afaq", "given" : "Saima", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehne", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Reilly", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lavery", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandrovcova", "given" : "Jana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wass", "given" : "Mark N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Kathryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oozageer", "given" : "Laticia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Ishminder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Hussaini", "given" : "Abtehale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mills", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grewal", "given" : "Jagvir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Panoulas", "given" : "Vasileios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewin", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Northwood", "given" : "Korrinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geoghegan", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yingrui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aitman", "given" : "Timothy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butcher", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "1", "12" ] ] }, "page" : "e102645", "title" : "The South Asian genome.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "108", "plainTextFormattedCitation" : "108", "previouslyFormattedCitation" : "108" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }108. As with metabolic traits, this discovery underscores the possibility that an entirely different set of genes may be important in governing birth weight for South Asians compared to those that have been identified as important in white Caucasians. This contention is supported by our findings that methylation of known birth weight genes were only associated with the outcome in white Caucasians and furthermore a genotype score of SNPs on these genes was also associated with birth only in this ethnic group. Large studies of CpG sites and SNPs associated with birth weight in South Asians may uncover genes representing pathways of importance in this group.4.4.5 Strengths and limitationsThis study has several key strengths. First of all, as recruitment for the START and CHILD cohorts was undertaken at various cities around Canada, our results are greatly generalizable. Second, as we conducted a stringent control for multiple testing, our results are likely robust and avoid false-positives discoveries. There were some limitations. Firstly, as our primary analysis included 234 South Asian and 250 Caucasian newborns, we were appropriately powered (>80%) to detect a change in birth weight as low as 0.05 kg for a 10% increase in methylation. It is thus possible that effect sizes lower than this were missed. Furthermore, if effect sizes for CpG sites showing heterogeneity were lower than 0.05 in South Asians, we were likely unable to detect them. Additionally, we were substantially underpowered to assess the effect of the tested SNPs with birth weight in our sample. We therefore explored this association with a genotype score. Thirdly, as blood collection protocol differed for the START and CHILD cohorts and the methylation data were processed separately, there exists a possibility of technical differences between studies, which may manifest as ethnic heterogeneity. Our analyses to explore sources of heterogeneity lend support to the possibility of this technical variation. However, these post-hoc analyses were comprised of small subgroups (i.e. 18 South Asians from CHILD cohort and 14 white Caucasians with a time of less than 2 hours between time of collection and processing) and thus should be interpreted with caution.4.5 Conclusions The results from our study support presence of ethnic heterogeneity at seven CpG sites on TCF7L2, IGF1, CALCR, HMGA2, and CDKAL1. Probe sites on these genes were robustly linked to birth weight in white Caucasians, but not in newborns of South Asian origin. Conversely, a genome-wide search of CpG sites associated with birth weight in South Asians revealed three novel suggestive signals, which were not associated with the outcome in Caucasians. Our results suggest that a unique sub-set of genes may be more important in modulating birth weight among South Asians. Chapter 5Discussion5.1 Overview of findingsNumerous studies have investigated reasons for variation in type 2 diabetes prevalence and related risk factors among people of South Asian and white Caucasian origin. Previous work from various geographic regions and age groups in South Asians has shown that this group is at a substantially higher risk for developing diabetesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1089/dia.2012.0236", "ISSN" : "1557-8593", "PMID" : "23151017", "abstract" : "AIM: This study was designed to determine the prevalence of glucose intolerance (prediabetes or diabetes) in children and adolescents in urban South India.\n\nSUBJECTS AND METHODS: Children (6-11 years old) and adolescents (12-19 years old) (n=1,519; 777 boys and 742 girls) were randomly selected from residential apartments representing the 10 corporation zones of Chennai city. Height, weight, waist circumference, body fat percentage, and blood pressure were measured using standardized techniques. Investigations included oral glucose tolerance test (OGTT), lipid profile, and fasting insulin. Insulin resistance (IR) was assessed by homeostasis model assessment (HOMA-IR).\n\nRESULTS: The overall prevalence of glucose intolerance was 3.7% but was higher in girls compared with boys (4.2% vs. 3.2%, P<0.001) and increased to 12.7% in girls with abdominal obesity. On univariate regression, the following risk factors showed significant association with glucose intolerance in girls: adolescent age group (odds ratio [OR] 2.94; confidence interval (CI) 1.12, 7.76), waist circumference (OR 4.45; CI 1.95, 10.14), body mass index (OR 2.73; CI 1.32, 5.65), acanthosis nigricans (OR 2.35; CI 1.14, 4.83), family history of diabetes (OR 2.52; CI 1.07, 5.92), and HOMA-IR (OR 9.30; CI 3.59, 24.12). On multivariate analysis, only family history of diabetes (OR 4.11; CI 1.28, 13.22; P=0.018) and HOMA-IR (OR 11.22; CI 4.19, 30.05; P<0.001) remained significant. In boys only HOMA-IR (OR 5.19; CI 1.54, 17.44; P=0.008) was associated with glucose intolerance.\n\nCONCLUSIONS: The prevalence of glucose intolerance is high in Asian Indian adolescents, particularly in girls with abdominal obesity.", "author" : [ { "dropping-particle" : "", "family" : "Ranjani", "given" : "Harish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonya", "given" : "Jagadesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anjana", "given" : "Ranjit M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes technology & therapeutics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "13-9", "title" : "Prevalence of glucose intolerance among children and adolescents in urban South India (ORANGE-2).", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1079/BJN19970114", "ISSN" : "0007-1145", "author" : [ { "dropping-particle" : "", "family" : "Simmons", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Rhys", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Nutrition", "id" : "ITEM-2", "issue" : "01", "issued" : { "date-parts" : [ [ "2007", "3", "9" ] ] }, "language" : "English", "page" : "5", "publisher" : "Cambridge University Press", "title" : "Dietary practices among Europeans and different South Asian groups in Coventry", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1093/ije/dyl245", "ISSN" : "0300-5771", "PMID" : "17510078", "abstract" : "The rates of coronary disease have accelerated dramatically amongst South Asians, driven to an important extent by the atherogenic dyslipidemia and type 2 diabetes that have become so common amongst them. These precursors of vascular disease appear at lower absolute amounts of adipose tissue in South Asians than in whites. In this paper, we set out a new hypothesis--the adipose tissue overflow hypothesis--to account for these findings. The adipose tissue mass within our bodies can be divided into three different compartments: superficial subcutaneous adipose tissue, deep subcutaneous adipose tissue and visceral adipose tissue. The superficial subcutaneous adipose tissue compartment is the primary compartment, is present throughout the body, and constitutes the vast majority of the adipose tissue in the lower limb. With energy excess, the secondary adipose tissue compartments--the deep subcutaneous (mainly upper body) and the visceral adipose tissue compartments--become more prominent. Superficial subcutaneous adipose tissue is relatively inert metabolically, whereas the other two compartments are characterized by higher transmembrane fatty acid flux rates and thus are more closely linked to dyslipidemia and dysglycemia. We hypothesize that the superficial subcutaneous adipose tissue compartment is larger in whites than in South Asians. If so, as obesity develops, South Asians exhaust the storage capacity of their superficial subcutaneous adipose tissue compartment before whites do and that is why they develop the metabolic complications of upper body obesity at lower absolute masses of adipose tissue than white people.", "author" : [ { "dropping-particle" : "", "family" : "Sniderman", "given" : "Allan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhopal", "given" : "Raj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sarrafzadegan", "given" : "Nizal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tchernof", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "2", "1" ] ] }, "page" : "220-5", "title" : "Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.cjca.2014.10.005", "ISSN" : "0828-282X", "author" : [ { "dropping-particle" : "", "family" : "Valera", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sohani", "given" : "Z.N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rana", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poirier", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "S.S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Canadian Journal of Cardiology", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2014" ] ] }, "language" : "English", "publisher" : "Elsevier", "title" : "The ethno-epidemiology of obesity", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.9778/cmajo.20130064", "ISSN" : "2291-0026", "PMID" : "25295238", "abstract" : "BACKGROUND: South Asians represent about 3% of the Canadian population and have a higher burden of certain cardiovascular risk factors and cardiovascular disease (CVD) compared with white people. The objective of this study was to review the literature to compare cardiovascular risk factors and disease management practices among adult South Asian and white Canadians.\n\nMETHODS: We searched MEDLINE, Embase, Cochrane and Cumulative Index to Nursing and Allied Health Literature databases from their inception through Feb. 17, 2014 and the reference lists of the selected articles. English-language studies of interventions and observational studies of biological mechanisms underlying CVD risk in South Asians conducted in Canada were eligible for inclusion. Where appropriate, we used random-effects meta-analyses to integrate results comparing the CVD risk profiles of South Asian and white Canadians.\n\nRESULTS: We included 50 articles (n = 5\u00a0805\u00a0313 individuals) in this review. Compared with white Canadians, South Asian Canadians had a higher prevalence and incidence of CVD, an increased prevalence of diabetes (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.81 to 2.80, p\u00a0<\u00a00.001) and hypertension (OR 1.11, 95% CI 1.02 to 1.22, p\u00a0=\u00a00.02), lower high-density lipoprotein cholesterol levels (mean difference -0.19\u00a0mmol/L, 95% CI -0.25 to -0.13 mmol/L, p\u00a0<\u00a00.001) and a higher percentage of body fat (men: absolute mean difference 3.23%, 95% CI 0.83% to 5.62%, p\u00a0=\u00a00.008; women: absolute mean difference 4.09%, 95% CI 3.46% to 4.72%, p\u00a0<\u00a00.001). South Asian people are also more sedentary, consume higher levels of carbohydrates and are less likely to smoke tobacco (OR 0.38, 95% CI 0.24 to 0.60, p\u00a0<\u00a00.001]) than white Canadians. No differences in access to diagnostic tests, outcomes following cardiovascular surgery or use of cardiac rehabilitation programs were apparent.\n\nINTERPRETATION: Compared with white people, South Asian people living in Canada have a higher prevalence and incidence of CVD and possess a unique cardiovascular risk profile.", "author" : [ { "dropping-particle" : "", "family" : "Rana", "given" : "Ayesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Souza", "given" : "Russell J", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kandasamy", "given" : "Sujane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lear", "given" : "Scott A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CMAJ open", "id" : "ITEM-5", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "7" ] ] }, "page" : "E183-91", "title" : "Cardiovascular risk among South Asians living in Canada: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "17,18,33,47,127", "plainTextFormattedCitation" : "17,18,33,47,127", "previouslyFormattedCitation" : "17,33,47,127,18" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }17,18,33,47,127. Literature to date supports differences in insulin sensitivity, compensatory beta-cell function, body fat distribution, and lipid profiles as underlying this increased riskADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ije/dys139", "ISSN" : "1464-3685", "PMID" : "22984147", "abstract" : "BACKGROUND: South Asian children and adults have a more adipose body composition compared with those of European ancestry. This is thought to be related to their increased risk of metabolic disorders. However, little is known about how early in life such differences are manifest.\n\nOBJECTIVE: To determine whether there are differences in fat mass (FM) and fat-free mass (FFM) between UK-born South Asians and White Europeans in infancy. Design A cross-sectional study of 30 South Asian and 30 White European infants aged 6-12 weeks. Mothers were recruited from clinics in London, and infants' FM and FFM were determined using air-displacement plethysmography (PeaPod(\u00ae)).\n\nRESULTS: In early infancy South Asians had less FFM than White Europeans [0.34 kg less, 95% confidence interval (CI): 0.15, 0.52], with a considerably weaker indication of them also having more FM (0.02 kg more, 95% CI: -0.14, 0.18). These differences persisted when the overall smaller body size of South Asian infants was taken into account. For a given total infant weight, the balance of body composition of South Asians was shifted by 0.16 kg (95% CI: 0.06, 0.25) from FFM to FM. The ethnic differences in the amount of FFM were almost completely accounted for by ethnic differences in the rate of growth in utero and length of gestation.\n\nCONCLUSIONS: The characteristic differences in body composition observed between adult South Asians and White Europeans are apparent in early infancy. Of particular note is that this is the first study to demonstrate that South Asians compared with White Europeans have reduced FFM in infancy. The early manifestation of this phenotype suggests that it is either genetic and/or determined through exposure to maternal physiology, rather than a consequence of behaviours or diet in childhood or at older ages.", "author" : [ { "dropping-particle" : "", "family" : "Stanfield", "given" : "Kristina M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wells", "given" : "Jonathan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fewtrell", "given" : "Mary S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frost", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leon", "given" : "David A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "10", "1" ] ] }, "page" : "1409-18", "title" : "Differences in body composition between infants of South Asian and European ancestry: the London Mother and Baby Study.", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00125-005-1689-3", "ISSN" : "0012-186X", "PMID" : "15759110", "abstract" : "AIMS/HYPOTHESIS: The aim of this study was to study differences in the prevalence of the metabolic syndrome and its associations with prevalent CHD according to ethnicity and sex.\n\nMETHODS: We performed a combined analysis of two population-based cross-sectional studies conducted between 1988 and 1991 that followed identical protocols. Participants (aged 40-69 years) comprised 2,346 Europeans (76% male), 1,711 South Asians (83% male) and 803 African-Caribbeans (57% male) resident in west London. Fasting blood, overnight urine collection, clinical and anthropometric measurements were performed. Clinical history or major ECG changes defined prevalent CHD. The metabolic syndrome was defined according to the criteria recommended by the World Health Organization (WHO) and the National Cholesterol Education Programme (NCEP).\n\nRESULTS: The prevalence of the metabolic syndrome was highest in South Asians (WHO, men 46%, women 31%; NCEP, men 29%, women 32%) and lowest in European women (WHO, 9%; NCEP, 14%). The prevalence of CHD was 10% in South Asian men, 9% in European men, 5-6% in African-Caribbeans and European women, and 2% in South Asian women. The metabolic syndrome was associated with prevalent CHD in European men [NCEP, odds ratio (OR)=1.6, 95% CI 1.2-2.4; WHO, OR=1.7, 95% CI 1.2-2.5] and South Asian men (NCEP, OR=2.1, 95% CI 1.5-3.1; WHO, OR=1.6, 95% CI 1.1-2.3). Associations with CHD were weaker in African-Caribbeans and were inconsistent among European women.\n\nCONCLUSIONS/INTERPRETATION: The current definitions of the metabolic syndrome give an inconsistent picture of cardiovascular disease risk when applied to different ethnic groups within the UK. Prospective studies are needed to validate workable ethnic-specific definitions.", "author" : [ { "dropping-particle" : "", "family" : "Tillin", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnston", "given" : "D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeigue", "given" : "P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godsland", "given" : "I F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2005", "4" ] ] }, "page" : "649-56", "title" : "Metabolic syndrome and coronary heart disease in South Asians, African-Caribbeans and white Europeans: a UK population-based cross-sectional study.", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/0140-6736(91)91164-P", "ISSN" : "01406736", "abstract" : "The hypothesis that the high mortality from coronary heart disease (CHD) in South Asians settled overseas compared with other populations is due to metabolic disturbances related to insulin resistance was tested in a population survey of 3193 men and 561 women aged 40-69 years in London, UK. The sample was assembled from industrial workforces and general practitioners' lists. In comparison with the European group, the South Asian group had a higher prevalence of diabetes (19% vs 4%), higher blood pressures, higher fasting and post-glucose serum insulin concentrations, higher plasma triglyceride. and lower HDL cholesterol concentrations. Mean waist-hip girth ratios and trunk skinfolds were higher in the South Asian than in the European group. Within each ethnic group waist-hip ratio was correlated with glucose intolerance, insulin, blood pressure, and triglyceride. These results confirm the existence of an insulin resistance syndrome, prevalent in South Asian populations and associated with a pronounced tendency to central obesity in this group. Control of obesity and greater physical activity offer the best chances for prevention of diabetes and CHD in South Asian people.", "author" : [ { "dropping-particle" : "", "family" : "McKeigue", "given" : "P.M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "M.G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Lancet", "id" : "ITEM-3", "issue" : "8738", "issued" : { "date-parts" : [ [ "1991", "2", "16" ] ] }, "page" : "382-386", "title" : "Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians", "type" : "article-journal", "volume" : "337" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "26,53,157", "plainTextFormattedCitation" : "26,53,157", "previouslyFormattedCitation" : "26,53,157" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }26,53,157. However, it is unclear whether this risk is predominantly due to genetic, epigenetic, environmental / behavioral factors, or a combination of allADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1479-5868-9-150", "ISSN" : "1479-5868", "PMID" : "23256686", "abstract" : "INTRODUCTION: The objective of this systematic mixed-methods review is to assess what is currently known about the levels of physical activity (PA) and sedentary time (ST) and to contextualize these behaviors among South Asian women with an immigrant background.\n\nMETHODS: A systematic search of the literature was conducted using combinations of the key words PA, ST, South Asian, and immigrant. A mixed-methods approach was used to analyze and synthesize all evidence, both quantitative and qualitative. Twenty-six quantitative and twelve qualitative studies were identified as meeting the inclusion criteria.\n\nRESULTS: Studies quantifying PA and ST among South Asian women showed low levels of PA compared with South Asian men and with white European comparison populations. However making valid comparisons between studies was challenging due to a lack of standardized PA measurement. The majority of studies indicated that South Asian women did not meet recommended amounts of PA for health benefits. Few studies assessed ST. Themes emerging from qualitative studies included cultural and structural barriers to PA, faith and education as facilitators, and a lack of understanding of the recommended amounts of PA and its benefits among South Asian women.\n\nCONCLUSIONS: Quantitative and qualitative evidence indicate that South Asian women do not perform the recommended level of PA for health benefits. Both types of studies suffer from limitations due to methods of data collection. More research should be dedicated to standardizing objective PA measurement and to understanding how to utilize the resources of the individuals and communities to increase PA levels and overall health of South Asian women.", "author" : [ { "dropping-particle" : "", "family" : "Babakus", "given" : "Whitney S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "Janice L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The international journal of behavioral nutrition and physical activity", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "150", "title" : "Physical activity among South Asian women: a systematic, mixed-methods review.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1079/BJN19970114", "ISSN" : "0007-1145", "author" : [ { "dropping-particle" : "", "family" : "Simmons", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Rhys", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Nutrition", "id" : "ITEM-2", "issue" : "01", "issued" : { "date-parts" : [ [ "2007", "3", "9" ] ] }, "language" : "English", "page" : "5", "publisher" : "Cambridge University Press", "title" : "Dietary practices among Europeans and different South Asian groups in Coventry", "type" : "article-journal", "volume" : "78" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1371/journal.pone.0102645", "ISSN" : "1932-6203", "PMID" : "25115870", "abstract" : "The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.", "author" : [ { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turro", "given" : "Ernest", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "William R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "Sian-Tsung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afzal", "given" : "Uzma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afaq", "given" : "Saima", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehne", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Reilly", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lavery", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandrovcova", "given" : "Jana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wass", "given" : "Mark N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Kathryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oozageer", "given" : "Laticia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Ishminder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Hussaini", "given" : "Abtehale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mills", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grewal", "given" : "Jagvir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Panoulas", "given" : "Vasileios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewin", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Northwood", "given" : "Korrinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geoghegan", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yingrui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aitman", "given" : "Timothy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butcher", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "1", "12" ] ] }, "page" : "e102645", "title" : "The South Asian genome.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "108,127,128", "plainTextFormattedCitation" : "108,127,128", "previouslyFormattedCitation" : "108,127,128" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }108,127,128. The specific aim of this thesis was to explore the role of genetic variants and epigenetic changes to explain the greater risk for type 2 diabetes and associated traits in South Asians.Findings from the meta-analysis of existing data on SNPs associated with type 2 diabetes (Chapter 2) show that no substantial differences in genetic risk likely exist for cosmopolitan SNPs present in both ethnicities. When population burden from all known common variants was examined using a genotype score, again no differences were foundADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-014-3354-1", "ISSN" : "1432-0428", "PMID" : "25145545", "abstract" : "AIMS/HYPOTHESIS: South Asians are up to four times more likely to develop type 2 diabetes than white Europeans. It is postulated that the higher prevalence results from greater genetic risk. To evaluate this hypothesis, we: (1) systematically reviewed the literature for single nucleotide polymorphisms (SNPs) predisposing to type 2 diabetes in South Asians; (2) compared risk estimates, risk alleles and risk allele frequencies of predisposing SNPs between South Asians and white Europeans; and (3) tested the association of novel SNPs discovered from South Asians in white Europeans.\n\nMETHODS: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane registry were searched for studies of genetic variants associated with type 2 diabetes in South Asians. Meta-analysis estimates for common and novel bi-allelic SNPs in South Asians were compared with white Europeans from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. The population burden from predisposing SNPs was assessed using a genotype score.\n\nRESULTS: Twenty-four SNPs from 21 loci were associated with type 2 diabetes in South Asians after meta-analysis. The majority of SNPs increase odds of the disorder by 15-35% per risk allele. No substantial differences appear to exist in risk estimates between South Asians and white Europeans from SNPs common to both groups, and the population burden also does not differ. Eight of the 24 are novel SNPs discovered from South Asian genome-wide association studies, some of which show nominal associations with type 2 diabetes in white Europeans.\n\nCONCLUSIONS/INTERPRETATION: Based on current literature there is no strong evidence to indicate that South Asians possess a greater genetic risk of type 2 diabetes than white Europeans.", "author" : [ { "dropping-particle" : "", "family" : "Sohani", "given" : "Zahra N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Wei Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014", "8", "22" ] ] }, "title" : "Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "132", "plainTextFormattedCitation" : "132", "previouslyFormattedCitation" : "132" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }132. Our conclusion was supported by additional advancements in literatureADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2897", "ISSN" : "1546-1718", "PMID" : "24509480", "abstract" : "To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.", "author" : [ { "dropping-particle" : "", "family" : "DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "South Asian Type 2 Diabetes (SAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mexican American Type 2 Diabetes (MAT2D) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Consortium", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Go", "given" : "Min Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Below", "given" : "Jennifer E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horikoshi", "given" : "Momoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Maggie C Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Xu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adair", "given" : "Linda S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atalay", "given" : "Mustafa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldassarre", "given" : "Damiano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bao", "given" : "Yuqian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "Ines", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "Graeme I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehm", "given" : "Bernhard O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burtt", "given" : "Noel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Qiuyin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carey", "given" : "Jason", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "Juliana C N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Li-Ching", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Tien-Jyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chang", "given" : "Yi-Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chien-Hsiun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Han", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yuan-Tsong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Nam H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Young Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chuang", "given" : "Lee-Ming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Couper", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crenshaw", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faire", "given" : "Ulf", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex S F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Donnelly", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorkhan", "given" : "Mozhgan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dupuis", "given" : "Josee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edkins", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erbel", "given" : "Raimund", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Escobedo", "given" : "Jorge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esko", "given" : "Tonu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eury", "given" : "Elodie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontanillas", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forsen", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fraser", "given" : "Ross M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gao", "given" : "Yutang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gertow", "given" : "Karl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gigante", "given" : "Bruna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamsten", "given" : "Anders", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Bok-Ghee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holmen", "given" : "Oddgeir L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hovingh", "given" : "Kees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hreidarsson", "given" : "Astradur B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Cheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunt", "given" : "Sarah E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ikegami", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jia", "given" : "Weiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jockel", "given" : "Karl-Heinz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Hyun Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "Wen Hong L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keinanen-Kiukaanniemi", "given" : "Sirkka M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "Ann M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Hassan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hyung-Lae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Sangsoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Young Jin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinnunen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klopp", "given" : "Norman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Korpi-Hyovalti", "given" : "Eeva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kravic", "given" : "Jasmina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krithika", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Ashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumate", "given" : "Jesus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kwak", "given" : "Soo Heon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lagou", "given" : "Vasiliki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakka", "given" : "Timo A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langford", "given" : "Cordelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leander", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jen-Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Nanette R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindholm", "given" : "Eero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Ching-Ti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jian Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Long", "given" : "Jirong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ma", "given" : "Ronald C W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mannisto", "given" : "Satu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metspalu", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyer", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mirza", "given" : "Ghazala", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mihailov", "given" : "Evelin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moebus", "given" : "Susanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muhleisen", "given" : "Thomas W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muller-Nurasyid", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Musk", "given" : "Bill", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamura", "given" : "Jiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakashima", "given" : "Eitaro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nilsson", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Njolstad", "given" : "Inger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nothen", "given" : "Markus M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohnaka", "given" : "Keizo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Twee Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Kyong Soo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parkin", "given" : "Melissa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pechlivanis", "given" : "Sonali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peters", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platou", "given" : "Carl G P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Jackie F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rallidis", "given" : "Loukianos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rauramaa", "given" : "Rainer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "N William", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rehnberg", "given" : "Emil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossin", "given" : "Elizabeth J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saaristo", "given" : "Timo E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saltevo", "given" : "Juha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saramies", "given" : "Jouko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Robert A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Segre", "given" : "Ayellet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sennblad", "given" : "Bengt", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shu", "given" : "Xiao Ou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigur[eth]sson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sivapalaratnam", "given" : "Suthesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "So", "given" : "Wing Yee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stancakova", "given" : "Alena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinbach", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strawbridge", "given" : "Rona J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sun", "given" : "Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syvanen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takayanagi", "given" : "Ryoichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teslovich", "given" : "Tanya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tikkanen", "given" : "Emmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trakalo", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tremoli", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trip", "given" : "Mieke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Fuu Jen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valladares-Salgado", "given" : "Adan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vedantam", "given" : "Sailaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veglia", "given" : "Fabrizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Congrong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wennauer", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilsgaard", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiltshire", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winckler", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Jer-Yuarn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamamoto", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Loic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yokota", "given" : "Mitsuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabaneh", "given" : "Delilah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zheng", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bowden", "given" : "Donald W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon Shin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "Nancy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cruz", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanis", "given" : "Craig L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jong-Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parra", "given" : "Esteban J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "3" ] ] }, "page" : "234-44", "publisher" : "Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.", "title" : "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.", "title-short" : "Nat Genet", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "104", "plainTextFormattedCitation" : "104", "previouslyFormattedCitation" : "104" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }104. This was not entirely surprising as the SNPs tested were identified from white Caucasian populations and then investigated in South Asians, increasing the likelihood of homogeneity. Therefore, if there is a difference in genetic risk between South Asians and Caucasians, it probably does not result from polymorphisms common to both groups. Consequently, we tested eight SNPs identified from South AsiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.2337/db12-1077", "ISSN" : "1939-327X", "PMID" : "23300278", "abstract" : "We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10\u207b\u00b3) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10\u207b\u2074) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 \u00d7 10\u207b\u2078) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10\u207b\u00b3) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10\u207b\u2074) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10\u207b\u2075 to < 10\u207b\u2077), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garavito", "given" : "Martha L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjonnes", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Weang Kee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yasushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirose", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jai Rup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "M Ilyas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maegawa", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobe", "given" : "Kazuyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-3", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "page" : "1746-55", "title" : "Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1371/journal.pgen.1001363", "ISSN" : "1553-7404", "PMID" : "21490949", "abstract" : "Recent large genome-wide association studies (GWAS) have identified multiple loci which harbor genetic variants associated with type 2 diabetes mellitus (T2D), many of which encode proteins not previously suspected to be involved in the pathogenesis of T2D. Most GWAS for T2D have focused on populations of European descent, and GWAS conducted in other populations with different ancestry offer a unique opportunity to study the genetic architecture of T2D. We performed genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945 controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians (977 cases, 1,169 controls). In addition to the search for novel variants implicated in T2D, these multi-ethnic cohorts serve to assess the transferability and relevance of the previous findings from European descent populations in the three major ethnic populations of Asia, comprising half of the world's population. Of the SNPs associated with T2D in previous GWAS, only variants at CDKAL1 and HHEX/IDE/KIF11 showed the strongest association with T2D in the meta-analysis including all three ethnic groups. However, consistent direction of effect was observed for many of the other SNPs in our study and in those carried out in European populations. Close examination of the associations at both the CDKAL1 and HHEX/IDE/KIF11 loci provided some evidence of locus and allelic heterogeneity in relation to the associations with T2D. We also detected variation in linkage disequilibrium between populations for most of these loci that have been previously identified. These factors, combined with limited statistical power, may contribute to the failure to detect associations across populations of diverse ethnicity. These findings highlight the value of surveying across diverse racial/ethnic groups towards the fine-mapping efforts for the casual variants and also of the search for variants, which may be population-specific.", "author" : [ { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Rick Twee-Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan-Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik-Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E-Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "editor" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Greg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "4" ] ] }, "page" : "e1001363", "publisher" : "Public Library of Science", "title" : "Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71\u201374", "plainTextFormattedCitation" : "71\u201374", "previouslyFormattedCitation" : "71\u201374" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71–74 in Caucasians. The results revealed that one SNP, SGCG rs9552911, was monomorphic in white Caucasians. The remaining SNPs, while polymorphic, were not robustly associated with type 2 diabetes in Caucasians, suggesting either existence of substantially different LD structures such that these seven SNPs tag lower frequency causal variants unique to South Asians, or lower effect sizes in white Caucasians due to ethnic specific gene–environment and/or gene–gene interactions. Although the meta-analysis in Chapter 2 presented important findings, the question of why South Asians are at a higher risk was not fully answered since the risk from individual common SNPs did not vary between the ethnic groups. Subsequently, Chapter 3 explored if variation in risk arises from an interaction of the genetic risk with abdominal obesity, a notable clinical risk factor among South AsiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2010.94", "ISSN" : "1930-739X", "PMID" : "20448537", "abstract" : "South Asians have a higher prevalence of cardiovascular disease (CVD) than Europeans. Studies have identified distinct subcompartments of subcutaneous adipose tissue (SAT) that provide insight into the relationship between abdominal obesity and metabolic risk factors in different ethnic groups. Our objective was to determine the relationship between SAT compartments and fat-free mass (FFM) between South Asian and European cohorts, and between men and women. Healthy Europeans and South Asians (n = 408) were assessed for FFM via dual energy X-ray absorptiometry, and SAT areas by computed tomography (CT). SAT was subdivided into superficial subcutaneous abdominal adipose tissue (SSAT) and deep subcutaneous abdominal adipose tissue (DSAT). Linear regression analyses were performed using DSAT and SSAT as separate dependent variables and FFM and ethnicity as primary independent variables adjusting for age, gender, income, education, and smoking status. Results showed that South Asian men had significantly higher amounts of DSAT (median 187.65 cm(2) vs. 145.15 cm(2), P < 0.001), SSAT (median 92.0 cm(2) vs. 76.1 cm(2), P = 0.046), and body fat mass (BFM) (25.1 kg vs. 22.6 kg, P = 0.049) than European men. In a fully adjusted model, South Asians showed significantly greater DSAT at any FFM than Europeans. Women had more SSAT at any given FFM than men and less DSAT at any given FFM than men, irrespective of ethnic background. In conclusion, South Asians had more DSAT than Europeans and men had relatively more DSAT than women. These data suggest that specific fat depots are influenced by ethnicity and gender; therefore, could provide insight into the relationship between ethnicity, gender and subsequent risk for CVD.", "author" : [ { "dropping-particle" : "", "family" : "Kohli", "given" : "Simi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sniderman", "given" : "Allan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tchernof", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lear", "given" : "Scott A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity (Silver Spring, Md.)", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "2177-83", "title" : "Ethnic-specific differences in abdominal subcutaneous adipose tissue compartments.", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "40", "plainTextFormattedCitation" : "40", "previouslyFormattedCitation" : "40" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }40. In agreement with the meta-analysis from Chapter 2, this primary analysis in an international cohort revealed that absolute genetic risk, measured as an un-weighted genotype score of SNPs involved in pancreatic beta-cell function did not vary among South Asians and Caucasians. The findings suggested that glycemic control deteriorated more in South Asians compared to white Caucasians even though the genetic risk was similar. In fact, an interaction existed between abdominal obesity and this genotype score in South Asians, such that those individuals with a genetically weak pancreas showed worse glucose control with increasing abdominal obesity. This interaction was not present in Caucasians suggesting that it is not innate differences in beta-cell function by itself, but a combined impact of reduced insulin secretion, from genetic impairments, and the effects of excess fat, from abdominal obesity, that leads to the ethnic variation in the prevalence of dysglycemia.The conclusions from Chapter 2 and 3 may appear at odds as the genotype score in Chapter 2 showed no ethnic heterogeneity, but the score tested in Chapter 3 had a bigger impact on glucose traits in South Asians compared to white Caucasians. These seemingly incongruent findings can be reconciled with the following considerations: (1) the outcomes tested were different between the studies; while Chapter 2 assessed type 2 diabetes, Chapter 3 explored the impact of a genotype score on fasting and AUC glucose. Previous research has shown a different subset of genetic variants at work for glucose traits versus type 2 diabetes, with only a partial overlapADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.520", "ISSN" : "1546-1718", "PMID" : "20081858", "abstract" : "Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Dupuis", "given" : "Jos\u00e9e", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gloyn", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00e4gi", "given" : "Reedik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rybin", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henneman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dehghan", "given" : "Abbas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franklin", "given" : "Christopher S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Navarro", "given" : "Pau", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perry", "given" : "John R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egan", "given" : "Josephine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lajunen", "given" : "Taina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grarup", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spars\u00f8", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doney", "given" : "Alex", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shrader", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cavalcanti-Proen\u00e7a", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumari", "given" : "Meena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zabena", "given" : "Carina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rocheleau", "given" : "Ghislain", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "An", "given" : "Ping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connell", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Payne", "given" : "Felicity", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sethupathy", "given" : "Praveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ardlie", "given" : "Kristin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ariyurek", "given" : "Yavuz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barter", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benediktsson", "given" : "Rafn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochud", "given" : "Murielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnefond", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00f6ttcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brunner", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bumpstead", "given" : "Suzannah J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Charpentier", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Gabe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crisponi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Day", "given" : "Ian N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "Jerome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fedson", "given" : "Annette C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Rosinsky", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frants", "given" : "Rune", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franzosi", "given" : "Maria Grazia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodarzi", "given" : "Mark O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graessler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gwilliam", "given" : "Rhian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadjadj", "given" : "Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "G\u00f6ran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammond", "given" : "Naomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Xijing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayward", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herder", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hicks", "given" : "Andrew A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hillman", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hingorani", "given" : "Aroon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hung", "given" : "Joe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Johnson", "given" : "Paul R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jula", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaakinen", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesaniemi", "given" : "Y Antero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kivimaki", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koskinen", "given" : "Seppo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten Ohm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lathrop", "given" : "G Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacquer", "given" : "Olivier", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "C\u00e9cile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyssenko", "given" : "Valeriya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahley", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manning", "given" : "Alisa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Larrad", "given" : "Mar\u00eda Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAteer", "given" : "Jarred B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCulloch", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meisinger", "given" : "Christa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morken", "given" : "Mario A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mukherjee", "given" : "Sutapa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naitza", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oostra", "given" : "Ben A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00f9", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pakyz", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paolisso", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattaro", "given" : "Cristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peden", "given" : "John F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pfeiffer", "given" : "Andreas F H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posthuma", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potter", "given" : "Simon C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Province", "given" : "Michael A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Psaty", "given" : "Bruce M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rathmann", "given" : "Wolfgang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rice", "given" : "Kenneth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ripatti", "given" : "Samuli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivadeneira", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roden", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rolandsson", "given" : "Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandbaek", "given" : "Annelli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayer", "given" : "Avan Aihie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seedorf", "given" : "Udo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sigurethsson", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sijbrands", "given" : "Eric J G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silveira", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Laila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Nicholas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nen", "given" : "Ann-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorand", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomi", "given" : "Tiinamaija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9 G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dijk", "given" : "Ko Willems", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Mandy", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Dhiraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visvikis-Siest", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vitart", "given" : "Veronique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vogelzangs", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Peter J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ward", "given" : "Kim L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wild", "given" : "Sarah H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willemsen", "given" : "Gonneke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jaqueline C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarnell", "given" : "John W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zelenika", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zethelius", "given" : "Bj\u00f6rn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meneton", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magnusson", "given" : "Patrik K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nathan", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Gordon H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwarz", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spranger", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serrano-R\u00edos", "given" : "Manuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lind", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "Paul W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marmot", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kao", "given" : "W H Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pankow", "given" : "James S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sampson", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pramstaller", "given" : "Peter Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Alan F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Augustine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duijn", "given" : "Cornelia M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aulchenko", "given" : "Yurii S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterworth", "given" : "Dawn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollenweider", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sladek", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meigs", "given" : "James B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Florez", "given" : "Jose C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2" ] ] }, "page" : "105-16", "title" : "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "10", "plainTextFormattedCitation" : "10", "previouslyFormattedCitation" : "10" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }10. (2) the SNPs tested did not overlap; in Chapter 3, we specifically examined SNPs with strong evidence for beta-cell function, while Chapter 2 was a meta-analysis of any reported SNP implicated in type 2 diabetes, regardless of the biological role. In fact, only 2 SNPs, TCF7L2 rs7903146 and SLC30A8 rs13266634, were common to both analyses. Lastly, (3) the populations tested varied substantially. A majority of the studies included in the meta-analysis from Chapter 2 recruited cases and controls from the general population (Supplementary Table 2.4), while some recruited cases from hospitals and diabetes clinics. Conversely, the EpiDREAM study solely included participants at high risk for developing diabetes, measured using family history and abdominal obesity, among other markers of metabolic health. Many of the participants had impaired fasting glucose or were impaired glucose intolerant. Consequently, it is possible that in the context of higher risk, where other metabolic abnormalities are already present, a genetic predisposition has a greater impact in South Asians than in the general population. Since differences in body fat composition among South Asians and Caucasians are present at birth and because low birth weight is strongly linked to type 2 diabetesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2008.886", "ISSN" : "1538-3598", "PMID" : "19109117", "abstract" : "CONTEXT: Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined.\n\nOBJECTIVE: To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults. Data Sources and\n\nSTUDY SELECTION: Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included.\n\nDATA EXTRACTION: Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations.\n\nDATA SYNTHESIS: Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight-type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I(2) = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight-type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no stron\u2026", "author" : [ { "dropping-particle" : "", "family" : "Whincup", "given" : "Peter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "Samantha J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huxley", "given" : "Rachel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cook", "given" : "Derek G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anazawa", "given" : "Sonoko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrett-Connor", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhargava", "given" : "Santosh K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Birgisdottir", "given" : "Brynd\u00eds E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlsson", "given" : "Sofia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rooij", "given" : "Susanne R", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dyck", "given" : "Roland F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Falkner", "given" : "Bonita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fall", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fors\u00e9n", "given" : "Tom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grill", "given" : "Valdemar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudnason", "given" : "Vilmundur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hulman", "given" : "Sonia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hypp\u00f6nen", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jeffreys", "given" : "Mona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leon", "given" : "David A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Minami", "given" : "Junichi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mishra", "given" : "Gita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Osmond", "given" : "Clive", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Power", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rich-Edwards", "given" : "Janet W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roseboom", "given" : "Tessa J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sachdev", "given" : "Harshpal Singh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syddall", "given" : "Holly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsdottir", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanhala", "given" : "Mauno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wadsworth", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yarbrough", "given" : "Donald E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "24", "issued" : { "date-parts" : [ [ "2008", "12", "24" ] ] }, "page" : "2886-97", "title" : "Birth weight and risk of type 2 diabetes: a systematic review.", "type" : "article-journal", "volume" : "300" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "216", "plainTextFormattedCitation" : "216", "previouslyFormattedCitation" : "216" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }216, Chapter 4 investigated the role of DNA methylation, an epigenetic mark that incorporates the genetic architecture and in-utero environment, in explaining ethnic variation of birth weight. Our findings suggest that genes involved in modifying birth weight in white Caucasians, and consequently the methylation levels at CpG sites on these genes, are less important in South Asians. To this end, our genome-wide search revealed three suggestive methylation sites important in modifying birth weight in South Asians, which were not associated in white Caucasian newborns. As these are suggestive signals, replication is warranted. Overall, our findings indicate that increased risk in metabolic traits among South Asians maybe due to a unique set of genes in this group.5.2 Methodological considerationsInterpretation of research findings is contingent on the conduct of methodological sound studies. Herein, the methodological context for the studies used in this thesis is discussed. In addition to challenges in classical epidemiological designs, such as selection bias and confounding, studies of genetic associations commonly face additional risk of bias, including appropriate sample size and power as well as quality of genotypingADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(05)67531-9", "ISSN" : "1474-547X", "PMID" : "16214603", "abstract" : "Genetic association studies are central to efforts to identify and characterise genomic variants underlying susceptibility to multifactorial disease. However, obtaining robust replication of initial association findings has proved difficult. Much of this inconsistency can be attributed to inadequacies in study design, implementation, and interpretation--inadequately powered sample groups are a major concern. Several additional factors affect the quality of any given association study, with appropriate sample-recruitment strategy, logical variant selection, minimum genotyping error, relevant data analysis, and valid interpretation all essential to generation of robust findings. Replication has a vital role in showing that associations that are identified reflect interesting biological processes rather than methodological quirks. For an unbiased view of the evidence for and against any particular association, study quality, rather than significance value, needs to play the dominant part.", "author" : [ { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9493", "issued" : { "date-parts" : [ [ "2005", "10", "8" ] ] }, "page" : "1315-23", "title" : "What makes a good genetic association study?", "type" : "article-journal", "volume" : "366" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "217", "plainTextFormattedCitation" : "217", "previouslyFormattedCitation" : "217" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }217. Details on genotyping quality have been discussed in the methods section of each chapter and will not be further elaborated here. Rather, the following discussion will focus on issues around sample selection, power, and confounding for the data used in this thesis. Subsequently, the next section will discuss the extent to which the findings from this thesis are generalizable and therefore externally valid.5.2.1 Internal validity5.2.1.1 Selection biasSelection bias results from systematic differences between participants included in the study and those not included; presumably, these differences can bias risk estimates reflecting the relationship between the exposure and outcomeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "ISBN: 978-1-4557-3733-8", "author" : [ { "dropping-particle" : "", "family" : "Gordis", "given" : "Leon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5th editio", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "number-of-pages" : "416", "publisher" : "Elsevier", "title" : "Epidemiology", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "218", "plainTextFormattedCitation" : "218", "previouslyFormattedCitation" : "218" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }218. Case-control and cross-sectional design is the mainstay of genetic association studies. In these types of studies, the chosen control group represents the population without the outcome of interest. Incorrect selection of the comparison group is a likely source of biasADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(05)67531-9", "ISSN" : "1474-547X", "PMID" : "16214603", "abstract" : "Genetic association studies are central to efforts to identify and characterise genomic variants underlying susceptibility to multifactorial disease. However, obtaining robust replication of initial association findings has proved difficult. Much of this inconsistency can be attributed to inadequacies in study design, implementation, and interpretation--inadequately powered sample groups are a major concern. Several additional factors affect the quality of any given association study, with appropriate sample-recruitment strategy, logical variant selection, minimum genotyping error, relevant data analysis, and valid interpretation all essential to generation of robust findings. Replication has a vital role in showing that associations that are identified reflect interesting biological processes rather than methodological quirks. For an unbiased view of the evidence for and against any particular association, study quality, rather than significance value, needs to play the dominant part.", "author" : [ { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9493", "issued" : { "date-parts" : [ [ "2005", "10", "8" ] ] }, "page" : "1315-23", "title" : "What makes a good genetic association study?", "type" : "article-journal", "volume" : "366" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "217", "plainTextFormattedCitation" : "217", "previouslyFormattedCitation" : "217" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }217. For example, if very sick cases are compared with healthy population controls, the effect size to estimate the impact of genetic variant on the disease may be inflated, and thus the most likely source of bias can come from choice of comparison groups.Meta-analysis: Selection bias in the context of a systematic review was examined by considering how representative the included studies were of the source population. All control and a majority of cases used in the meta-analysis were derived from general clinics through community and health promotion fairs. Other cases were recruited from diabetes / endocrinology clinics as well as general clinics in hospitals. Although this lowers the possibility of systematic bias, it cannot be absolutely ruled out since some cases were taken from high-risk diabetes clinics and hospitals, possibly representing very sick individuals with comorbidities. Furthermore, none of the studies compared characteristics of included participants with those refusing to participate making it difficult to holistically examine possible bias. The EpiDREAM study: As an international prospective design, the possibility of selection bias in the EpiDREAM study is minimized since the sample is representative of the overall population as individuals from many socio-economic, regional, and cultural backgrounds are included. Additionally, the comparison groups were taken from the same source. The study includes a multi-ethnic sample of 24,595 individuals from 191 sites in 21 countriesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-010-1710-3", "ISSN" : "0012-186X", "PMID" : "20372875", "abstract" : "AIMS/HYPOTHESES: We determined: (1) which of BMI, waist circumference, hip circumference and WHR has the strongest association and explanatory power for newly diagnosed type 2 diabetes and glucose status; and (2) the impact of considering two measures simultaneously. We also explored variation in anthropometric associations by sex and ethnicity.\n\nMETHODS: We performed cross-sectional analysis of 22,293 men and women who were from five ethnic groups and 21 countries, and at risk of developing type 2 diabetes. Standardised anthropometric associations with type 2 diabetes and AUC of glucose status from OGTT (AUC(OGTT)) were determined using multiple regression. Explanatory power was assessed using the c-statistic and adjusted r (2).\n\nRESULTS: An increase in BMI, waist circumference or WHR had similar positive associations with type 2 diabetes, AUC(OGTT) and explanatory power after adjustment for age, sex, smoking and ethnicity (p < 0.01). However, using BMI and WHR together resulted in greater explanatory power than with other models (p < 0.01). Associations were strongest when waist circumference and hip circumference were used together, a combination that had greater explanatory power than other models except for BMI and WHR together (p < 0.01). Results were directionally similar according to sex and ethnicity; however, significant variations in associations were observed among these subgroups.\n\nCONCLUSIONS/INTERPRETATION: The combination of BMI and WHR, or of waist circumference and hip circumference has the best explanatory power for type 2 diabetes and glucose status compared with a single anthropometric measure. Measurement of waist circumference and hip circumference is required to optimally identify people at risk of type 2 diabetes and people with elevated glucose levels.", "author" : [ { "dropping-particle" : "", "family" : "Koning", "given" : "L.", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "H. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dagenais", "given" : "G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "S. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "4", "7" ] ] }, "page" : "1322-1330", "title" : "Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2337/dc12-2553", "ISSN" : "1935-5548", "PMID" : "23603917", "abstract" : "OBJECTIVE: To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.\n\nRESEARCH DESIGN AND METHODS: In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.\n\nRESULTS: Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).\n\nCONCLUSIONS: T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Changchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xiaohe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Jackie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keavney", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudet", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "2836-42", "title" : "Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62,149", "plainTextFormattedCitation" : "62,149", "previouslyFormattedCitation" : "62,149" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62,149. However, it should be noted that the study aimed to include only those individuals at a high-risk for developing dysglycemia, established using family history, ethnicity, gestational diabetes, and abdominal obesity. As a result, data used to establish the genetic effect of variants on type 2 diabetes and other glycemic measures does not reflect risk in the general population. Since this is a high-risk group, the effect of genes is likely over-represented. Nonetheless, as ours was an ethnic comparison for which both South Asians and Caucasians were recruited using the same study protocol, use of a high-risk group does not bias our results on ethnic variation. Furthermore, to circumvent bias from ascertainment, we matched South Asians and Caucasians on age and sex. Since the match was imperfect, the possibility of bias from selection and ascertainment cannot be completely obviated. START and CHILD birth cohorts: START is a birth cohort of South Asian mother-baby pairs living in Canada. Mothers in the first trimester of their pregnancy were recruited from three hospitals in the Peel region, where South Asians comprise 18% of the populationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2458-13-79", "ISSN" : "1471-2458", "PMID" : "23356884", "abstract" : "BACKGROUND: People who originate from the Indian subcontinent (South Asians) suffer among the highest rates of type 2 diabetes in the world. Prior evidence suggests that metabolic risk factors develop early in life and are influenced by maternal and paternal behaviors, the intrauterine environment, and genetic factors. The South Asian Birth Cohort Study (START) will investigate the environmental and genetic basis of adiposity among 750 South Asian offspring recruited from highly divergent environments, namely, rural and urban India and urban Canada.\n\nMETHODS: Detailed information on health behaviors including diet and physical activity, and blood samples for metabolic parameters and DNA are collected from pregnant women of South Asian ancestry who are free of significant chronic disease. They also undergo a provocative test to diagnose impaired glucose tolerance and gestational diabetes. At delivery, cord blood and newborn anthropometric indices (i.e. birth weight, length, head circumference and skin fold thickness) are collected. The mother and growing offspring are followed prospectively and information on the growth trajectory, adiposity and health behaviors will be collected annually up to age 3 years. Our aim is to recruit a minimum of 750 mother-infant pairs equally divided between three divergent environments: rural India, urban India, and Canada.\n\nSUMMARY: The START cohort will increase our understanding of the environmental and genetic determinants of adiposity and related metabolic abnormalities among South Asians living in India and Canada.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vasudevan", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Milan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "Katherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurpad", "given" : "Anura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Koon K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinivasan", "given" : "Krishnamachari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC public health", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "79", "title" : "Rationale and design of South Asian Birth Cohort (START): a Canada-India collaborative study.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "63", "plainTextFormattedCitation" : "63", "previouslyFormattedCitation" : "63" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }63. Similarly, CHILD is a population-based cohort of mother-baby dyads across four major Canadian citiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/jes.2015.7", "ISSN" : "1559-064X", "PMID" : "25805254", "abstract" : "The Canadian Healthy Infant Longitudinal Development birth cohort was designed to elucidate interactions between environment and genetics underlying development of asthma and allergy. Over 3600 pregnant mothers were recruited from the general population in four provinces with diverse environments. The child is followed to age 5 years, with prospective characterization of diverse exposures during this critical period. Key exposure domains include indoor and outdoor air pollutants, inhalation, ingestion and dermal uptake of chemicals, mold, dampness, biological allergens, pets and pests, housing structure, and living behavior, together with infections, nutrition, psychosocial environment, and medications. Assessments of early life exposures are focused on those linked to inflammatory responses driven by the acquired and innate immune systems. Mothers complete extensive environmental questionnaires including time-activity behavior at recruitment and when the child is 3, 6, 12, 24, 30, 36, 48, and 60 months old. House dust collected during a thorough home assessment at 3-4 months, and biological specimens obtained for multiple exposure-related measurements, are archived for analyses. Geo-locations of homes and daycares and land-use regression for estimating traffic-related air pollution complement time-activity-behavior data to provide comprehensive individual exposure profiles. Several analytical frameworks are proposed to address the many interacting exposure variables and potential issues of co-linearity in this complex data set.Journal of Exposure Science and Environmental Epidemiology advance online publication, 25 March 2015; doi:10.1038/jes.2015.7.", "author" : [ { "dropping-particle" : "", "family" : "Takaro", "given" : "Tim K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allen", "given" : "Ryan W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Allan B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Befus", "given" : "A Dean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brauer", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "Joanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lefebvre", "given" : "Diana L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lou", "given" : "Wendy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandhane", "given" : "Piush J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McLean", "given" : "Kathleen E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Gregory", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sbihi", "given" : "Hind", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shu", "given" : "Huan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subbarao", "given" : "Padmaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turvey", "given" : "Stuart E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeng", "given" : "Leilei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sears", "given" : "Malcolm R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brook", "given" : "Jeffrey R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of exposure science & environmental epidemiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015", "3", "25" ] ] }, "title" : "The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: assessment of environmental exposures.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "184", "plainTextFormattedCitation" : "184", "previouslyFormattedCitation" : "184" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }184. Though similar in design, small differences in inclusion and exclusion criteria do exist. Furthermore, both studies recruited from hospital settings and as a result missed pregnant mothers using birthing centers and other alternative settings. There may be systematic differences between these groups, including infant outcomes and socioeconomic status, among othersADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajog.2010.05.028", "ISSN" : "1097-6868", "PMID" : "20598284", "abstract" : "OBJECTIVE: We sought to systematically review the medical literature on the maternal and newborn safety of planned home vs planned hospital birth.\n\nSTUDY DESIGN: We included English-language peer-reviewed publications from developed Western nations reporting maternal and newborn outcomes by planned delivery location. Outcomes' summary odds ratios with 95% confidence intervals were calculated.\n\nRESULTS: Planned home births were associated with fewer maternal interventions including epidural analgesia, electronic fetal heart rate monitoring, episiotomy, and operative delivery. These women were less likely to experience lacerations, hemorrhage, and infections. Neonatal outcomes of planned home births revealed less frequent prematurity, low birthweight, and assisted newborn ventilation. Although planned home and hospital births exhibited similar perinatal mortality rates, planned home births were associated with significantly elevated neonatal mortality rates.\n\nCONCLUSION: Less medical intervention during planned home birth is associated with a tripling of the neonatal mortality rate.", "author" : [ { "dropping-particle" : "", "family" : "Wax", "given" : "Joseph R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lucas", "given" : "F Lee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lamont", "given" : "Maryanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinette", "given" : "Michael G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cartin", "given" : "Angelina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blackstone", "given" : "Jacquelyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of obstetrics and gynecology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "9" ] ] }, "page" : "243.e1-8", "title" : "Maternal and newborn outcomes in planned home birth vs planned hospital births: a metaanalysis.", "type" : "article-journal", "volume" : "203" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "219", "plainTextFormattedCitation" : "219", "previouslyFormattedCitation" : "219" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }219. Additionally, as the study recruitment and follow-up largely took place in urban / metropolitan regions, rural families were inherently excluded or under-representedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmj.307.6917.1458", "ISSN" : "0959-8138", "abstract" : "OBJECTIVE--To compare proportions of low birthweight babies and mean heights of schoolchildren between rural and urban areas at different levels of social deprivation. DESIGN--Cross sectional population based study classifying cases by Townsend material deprivation index of enumeration district of residence and by rural areas, small towns, and large towns. SETTING--Northumberland Health District. SUBJECTS--18,930 singleton infants delivered alive during January 1985 to September 1990 and resident in Northumberland in October 1990; 9055 children aged 5 to 8 1/2 years attending Northumberland schools in the winter of 1989-90. MAIN OUTCOME MEASURES--Odds ratios for birth weight less than 2800 g; difference in mean height measured by standard deviation (SD) score. RESULTS--Between the most deprived and most affluent 20% of enumeration districts the odds ratio for low birth weight adjusted for rural or urban setting was 1.71 (95% confidence interval 1.51 to 1.93) and the difference in mean height -0.232 SD score (-0.290 to -0.174). Between large towns and rural areas the odds ratio for low birth weight adjusted for deprivation was 1.37 (1.23 to 1.53) and the difference in mean height -0.162 SD score (-0.214 to -0.110). Results for small towns were intermediate between large towns and rural areas. CONCLUSIONS--Inequalities in birth weight and height exist in all rural and urban settings between deprived and affluent areas. In addition, there is substantial disadvantage to living in urban areas compared with rural areas which results from social or environmental factors unrelated to current levels of deprivation.", "author" : [ { "dropping-particle" : "", "family" : "Reading", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raybould", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvis", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ", "id" : "ITEM-1", "issue" : "6917", "issued" : { "date-parts" : [ [ "1993", "12", "4" ] ] }, "page" : "1458-1462", "title" : "Deprivation, low birth weight, and children's height: a comparison between rural and urban areas.", "type" : "article-journal", "volume" : "307" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "220", "plainTextFormattedCitation" : "220", "previouslyFormattedCitation" : "220" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }220. Previous research on our main outcome, birth weight, suggests that possible bias against inclusion from rural regions likely led to an under-representation of children born with extremely low birth weight. Conversely, planned non-hospital births have been associated with healthier babies, usually with higher birth weights. Overall, the mean birth weights for both South Asian and European groups reflected published Canadian averagesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1701-2163", "PMID" : "19497151", "abstract" : "OBJECTIVE: To determine the risk that newborn infants of East Asian and South Asian ancestry may be misclassified as small for gestational age (SGA).\n\nMETHODS: We performed a single-centre, cross-sectional study of a cohort of liveborn infants born to women who had been born in Canada (n = 2362), East Asia (n = 1565) and South Asia (n = 753) and generated smoothed birth weight curves for males and females. We determined the rate of misclassification of infants of East Asian and South Asian maternal origin as SGA, using conventional weight centile cut-offs, rather than those specific to each ethnic group.\n\nRESULTS: Infants of Canadian-born mothers had a mean birth weight that was 144 g and 218 g greater than newborns of mothers of East Asian and South Asian origin, respectively. Using the 3rd centile cut-off for infants of Canadian-born mothers, 7 per 1000 female and 14 per 1000 male infants of East Asian maternal origin were potentially miscategorized as SGA at birth. Among female and male infants of mothers of South Asian origin, the corresponding rates were 29 and 46 per 1000.\n\nCONCLUSION: Birth weight curves may need to be modified for newborns of East Asian and South Asian parentage to make a more accurate diagnosis of SGA.", "author" : [ { "dropping-particle" : "", "family" : "Ray", "given" : "Joel G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiang", "given" : "Depeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sgro", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Rajiv", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Gita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mamdani", "given" : "Muhammad M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obst\u00e9trique et gyn\u00e9cologie du Canada : JOGC", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "322-30", "title" : "Thresholds for small for gestational age among newborns of East Asian and South Asian ancestry.", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "221", "plainTextFormattedCitation" : "221", "previouslyFormattedCitation" : "221" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }221, and though the possibility of selection bias cannot be entirely precluded, there is likely little effect of bias from ascertainment in these cohorts.5.2.1.2 Sample size and powerAppropriately powered samples are a key determinant of quality in genetic association studies, as many common variants can have a low relative-risk and rare variants have lower frequencies. Inappropriately powered studies are either unable to detect the effect of a genetic variant on an outcome or report effect sizes for genetic variants that are overestimatesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(05)67531-9", "ISSN" : "1474-547X", "PMID" : "16214603", "abstract" : "Genetic association studies are central to efforts to identify and characterise genomic variants underlying susceptibility to multifactorial disease. However, obtaining robust replication of initial association findings has proved difficult. Much of this inconsistency can be attributed to inadequacies in study design, implementation, and interpretation--inadequately powered sample groups are a major concern. Several additional factors affect the quality of any given association study, with appropriate sample-recruitment strategy, logical variant selection, minimum genotyping error, relevant data analysis, and valid interpretation all essential to generation of robust findings. Replication has a vital role in showing that associations that are identified reflect interesting biological processes rather than methodological quirks. For an unbiased view of the evidence for and against any particular association, study quality, rather than significance value, needs to play the dominant part.", "author" : [ { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9493", "issued" : { "date-parts" : [ [ "2005", "10", "8" ] ] }, "page" : "1315-23", "title" : "What makes a good genetic association study?", "type" : "article-journal", "volume" : "366" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "217", "plainTextFormattedCitation" : "217", "previouslyFormattedCitation" : "217" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }217.Meta-analysis: Our meta-analysis found 15 SNPs associated with type 2 diabetes in South Asians that also showed an effect in Caucasians. Data were available on an additional 9 SNPs that are associated with the outcome in Caucasians, but were not replicated in South Asians. Our main analysis, with a maximum of 25,984 and a minimum of 1,024 cases, was appropriately powered to detect an effect size of 1.05 at an allele frequency as low as 15% and 1.20 at an allele frequency of 30% (Figure 5.1). For the SNPs not associated with type 2 diabetes in South Asians, it is likely that we were not appropriately powered to detect a significant association.Figure 5. SEQ Figure_5. \* ARABIC 1 Power calculations for case-control association studies of unrelated individuals. Curves represent the number of individuals, at a case-control ratio of 1:1, required to achieve 80% power for a disease prevalence of 10% at α = 0.05.The EpiDREAM study: To assess whether an ethnic interaction existed in the effect of the beta-cell genotype score on glucose traits, we had >90% power (at α=0.025 to account for inclusion of a 2-way interaction term) in our sample of 5,302 individuals to detect an interaction parameter as low as 0.005. To test a three-way interaction (ethnicity*genotype score*WaistadjHip), our power decreased to 85% to detect an interaction parameter as low as 0.005 using an α=0.01. Within our sample, we report a two-way interaction parameter of 0.05 on fasting glucose and 0.15 on AUC glucose. Similarly, we found a three-way interaction parameter of 0.005 on fasting glucose and 0.01 on AUC glucose.START and CHILD birth cohorts: Our analysis investigating the effect of CpG probe sites on birth weight (adjusted for gestational age and sex), separately for white Caucasians and South Asian newborns, had a power of 80% to detect a nominal association for a β-coefficient of at least 0.05 for a 10% increase in methylation. All detected effect sizes, however, exceeded this minimum. We applied a false discovery rate q-value of 0.05 to avoid bias from multiple testing. For our genome-wide analysis, at a Bonferroni corrected α threshold of 1.3x10-7, we had 80% power to detect a β-coefficient of 0.2. Hence, at this genome-wide level, we were underpowered.5.2.1.3 ConfoundingBias from confounding arises when an extraneous variable, correlated with the exposure and outcome, is not considered in the analysis of the exposure-outcome relationshipADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "ISBN: 978-1-4557-3733-8", "author" : [ { "dropping-particle" : "", "family" : "Gordis", "given" : "Leon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5th editio", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "number-of-pages" : "416", "publisher" : "Elsevier", "title" : "Epidemiology", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "218", "plainTextFormattedCitation" : "218", "previouslyFormattedCitation" : "218" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }218. Inclusion of this confounder in a statistical model can affect the magnitude, strength, and direction of the exposure-outcome relationshipADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "ISBN: 978-1-4557-3733-8", "author" : [ { "dropping-particle" : "", "family" : "Gordis", "given" : "Leon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5th editio", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "number-of-pages" : "416", "publisher" : "Elsevier", "title" : "Epidemiology", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "218", "plainTextFormattedCitation" : "218" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }218. Confounding bias can be avoided by appropriate identification and adjustment of potential confounders in the study design and statistical analysis. On the other hand, it should be noted that adjusting for confounders that share heritability with the outcome can bias results of the association testADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajhg.2014.12.021", "ISSN" : "1537-6605", "PMID" : "25640676", "abstract" : "In recent years, a number of large-scale genome-wide association studies have been published for human traits adjusted for other correlated traits with a genetic basis. In most studies, the motivation for such an adjustment is to discover genetic variants associated with the primary outcome independently of the correlated trait. In this report, we contend that this objective is fulfilled when the tested variants have no effect on the covariate or when the correlation between the covariate and the outcome is fully explained by a direct effect of the covariate on the outcome. For all other scenarios, an unintended bias is introduced with respect to the primary outcome as a result of the adjustment, and this bias might lead to false positives. Here, we illustrate this point by providing examples from published genome-wide association studies, including large meta-analysis of waist-to-hip ratio and waist circumference adjusted for body mass index (BMI), where genetic effects might be biased as a result of adjustment for body mass index. Using both theory and simulations, we explore this phenomenon in detail and discuss the ramifications for future genome-wide association studies of correlated traits and diseases.", "author" : [ { "dropping-particle" : "", "family" : "Aschard", "given" : "Hugues", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilhj\u00e1lmsson", "given" : "Bjarni J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joshi", "given" : "Amit D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015", "2", "5" ] ] }, "page" : "329-39", "title" : "Adjusting for heritable covariates can bias effect estimates in genome-wide association studies.", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "222", "plainTextFormattedCitation" : "222", "previouslyFormattedCitation" : "222" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }222. Therefore, covariates and confounders should be chosen carefully.Meta-analysis: Effects for SNPs associated with type 2 diabetes were pooled under an additive model of inheritance. Because of the unavailability of consistently adjusted data, since the included studies adjusted for different combinations of potential confounders, we pooled unadjusted allelic odds ratios. Although age and sex are often adjusted for in genetic case-control studies, they are likely associated with the outcome, i.e. type 2 diabetes, but are unlikely to be related to the genotype. As a result, these variables are not confounders and adjustment can often come at the cost of loss in powerADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1003096", "ISSN" : "1553-7404", "PMID" : "23162385", "author" : [ { "dropping-particle" : "", "family" : "Mefford", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witte", "given" : "John S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2012", "1", "8" ] ] }, "page" : "e1003096", "title" : "The Covariate's Dilemma.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "223", "plainTextFormattedCitation" : "223", "previouslyFormattedCitation" : "223" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }223. A possible confounder to consider, however, is BMI as some type 2 diabetes variants can also be associated with BMI; a classic example of this is FTOADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-012-2478-4", "ISSN" : "1432-0428", "PMID" : "22297584", "author" : [ { "dropping-particle" : "", "family" : "Meyre", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "4" ] ] }, "page" : "873-6", "title" : "Is FTO a type 2 diabetes susceptibility gene?", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "224", "plainTextFormattedCitation" : "224", "previouslyFormattedCitation" : "224" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }224. Since our analysis did not adjust for BMI, confounding bias cannot be entirely avoided. Particularly, if BMI is more strongly associated with a genetic variant in one ethnic group compared to another, the ethnic comparison may be biased. Often, the most important confounder in genetic studies is population stratificationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0123751438", "abstract" : "According to the National Institute of Health, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. Whole genome information, when combined with clinical and other phenotype data, offers the potential for increased understanding of basic biological processes affecting human health, improvement in the prediction of disease and patient care, and ultimately the realization of the promise of personalized medicine. In addition, rapid advances in understanding the patterns of human genetic variation and maturing high-throughput, cost-effective methods for genotyping are providing powerful research tools for identifying genetic variants that contribute to health and disease. (good paragraph)This burgeoning science merges the principles of statistics and genetics studies to make sense of the vast amounts of information available with the mapping of genomes. In order to make the most of the information available, statistical tools must be tailored and translated for the analytical issues which are original to large-scale association studies. This book will provide researchers with advanced biological knowledge who are entering the field of genome-wide association studies with the groundwork to apply statistical analysis tools appropriately and effectively. With the use of consistent examples throughout the work, chapters will provide readers with best practice for getting started (design), analyzing, and interpreting data according to their research interests. Frequently used tests will be highlighted and a critical analysis of the advantages and disadvantage complimented by case studies for each will provide readers with the information they need to make the right choice for their research. Additional tools including links to analysis tools, tutorials, and references will be available electronically to ensure the latest information is available.* Easy access to key information including advantages and disadvantage of tests for particular applications, identification of databases, languages and their capabilities, data management risks, frequently used tests* Extensive list of references including links to tutorial websites* Case studies and Tips and Tricks", "editor" : [ { "dropping-particle" : "", "family" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "number-of-pages" : "340", "publisher" : "Academic Press", "title" : "Analysis of Complex Disease Association Studies: A Practical Guide", "type" : "book", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "225", "plainTextFormattedCitation" : "225", "previouslyFormattedCitation" : "225" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }225. As the meta-analysis was restricted to only South Asians, this confounder was less concerning. Although, it is noteworthy that sub-structure within the South Asian group was not addressed.The EpiDREAM study: The analysis using data from this study examined the variation in association of a beta-cell genotype score and glucose traits for South Asians and Caucasians (using a 2-way interaction term) and a variation in the relationship of adiposity with the genotype score by ethnicity on the glucose traits (using a 3-way interaction term). The South Asian and white Caucasian cohorts were matched on age and sex to avoid ascertainment bias. Furthermore, all analyses were adjusted for age, sex, ethnicity, and BMI to address any possibility of residual confounding for age and sex since this was an imperfect match and to avoid confounding from BMI and population stratification. Our analyses showed a strong and statistically significant effect of the genotype score independent of these other factors. START and CHILD birth cohorts: As DNA methylation analyses are a relatively new field of study, commonly accepted norms around confounding variables have not yet been established. To select confounders, we investigated the association of potential confounders with the outcome (i.e. birth weight and length) and predictor (i.e. methylation at CpG sites). While sex and gestational age were consistently associated with birth weight / length, there was inconsistent evidence of association with methylation levels, i.e. some probe sites showed a significant association while others did not. Moreover, we found genotypes to also be inconsistently associated with methylation. Since the outcome was a continuous variable, we did not expect to lose power from adjusting for multiple covariates; in fact, including a non-confounding covariate can be beneficial as it explains some of the variability in the outcome, hence reducing noise and increasing power to detect novel associationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1003096", "ISSN" : "1553-7404", "PMID" : "23162385", "author" : [ { "dropping-particle" : "", "family" : "Mefford", "given" : "Joel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witte", "given" : "John S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2012", "1", "8" ] ] }, "page" : "e1003096", "title" : "The Covariate's Dilemma.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "223", "plainTextFormattedCitation" : "223", "previouslyFormattedCitation" : "223" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }223. Our analysis included the aforementioned covariates and thus reduced the potential for bias from confounding.5.2.2 External validityExternal validity pertains to the process of generalizing the findings from the sample studied to the population at-large. Within the meta-analysis, to ensure external validity, a representative sample of the literature was acquired using a thorough search strategy, with input from a McMaster University librarian, and via search of a variety of databases. As previously described, a majority of studies were derived from the general population, with the exception of some for which cases were recruited from diabetes clinics / hospitals. This type of study design is more feasible than a community design where the study team must visit individual households or community dwellings. Though feasible, the risk estimates established for the effect of genetic variants on diabetes from such studies may not be applicable to less sick, more general populations. It should be noted, however, that no substantial between-study heterogeneity was uncovered from inclusion of such studies, and thus the estimates are likely representative of a general population. Furthermore, with the exception of the Sikh Diabetes StudyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2350-9-59", "ISSN" : "1471-2350", "PMID" : "18598350", "abstract" : "BACKGROUND: Recent genome-wide association (GWA) studies have identified several unsuspected genes associated with type 2 diabetes (T2D) with previously unknown functions. In this investigation, we have examined the role of 9 most significant SNPs reported in GWA studies: [peroxisome proliferator-activated receptor gamma 2 (PPARG2; rs 1801282); insulin-like growth factor two binding protein 2 (IGF2BP2; rs 4402960); cyclin-dependent kinase 5, a regulatory subunit-associated protein1-like 1 (CDK5; rs7754840); a zinc transporter and member of solute carrier family 30 (SLC30A8; rs13266634); a variant found near cyclin-dependent kinase inhibitor 2A (CDKN2A; rs10811661); hematopoietically expressed homeobox (HHEX; rs 1111875); transcription factor-7-like 2 (TCF7L2; rs 10885409); potassium inwardly rectifying channel subfamily J member 11(KCNJ11; rs 5219); and fat mass obesity-associated gene (FTO; rs 9939609)].\n\nMETHODS: We genotyped these SNPs in a case-control sample of 918 individuals consisting of 532 T2D cases and 386 normal glucose tolerant (NGT) subjects of an Asian Sikh community from North India. We tested the association between T2D and each SNP using unconditional logistic regression before and after adjusting for age, gender, and other covariates. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels using multiple linear regression analysis.\n\nRESULTS: Four of the nine SNPs revealed a significant association with T2D; PPARG2 (Pro12Ala) [odds ratio (OR) 0.12; 95% confidence interval (CI) (0.03-0.52); p = 0.005], IGF2BP2 [OR 1.37; 95% CI (1.04-1.82); p = 0.027], TCF7L2 [OR 1.64; 95% CI (1.20-2.24); p = 0.001] and FTO [OR 1.46; 95% CI (1.11-1.93); p = 0.007] after adjusting for age, sex and BMI. Multiple linear regression analysis revealed significant association of two of nine investigated loci with diabetes-related quantitative traits. The 'C' (risk) allele of CDK5 (rs 7754840) was significantly associated with decreased HDL-cholesterol levels in both NGT (p = 0.005) and combined (NGT and T2D) (0.005) groups. The less common 'C' (risk) allele of TCF7L2 (rs 10885409) was associated with increased LDL-cholesterol (p = 0.010) in NGT and total and LDL-cholesterol levels (p = 0.008; p = 0.003, respectively) in combined cohort.\n\nCONCLUSION: To our knowledge, this is first study reporting the role of some recently emerged loci with T2D in a high risk population of As\u2026", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Shizhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jairup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrell", "given" : "Robert E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nath", "given" : "Swapan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "Mohammed I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "59", "title" : "Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "94", "plainTextFormattedCitation" : "94", "previouslyFormattedCitation" : "94" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94 and an Aggarwal population studyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-1809.2010.00580.x", "ISSN" : "1469-1809", "PMID" : "20597906", "abstract" : "The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18-clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan-based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p-value = 0.00191; p-value = 0.00179, respectively), and odds ratios of 2.1 (dominant-model) and 2.0 (recessive-model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist-Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single-SNP, combined-SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally-learned sedentary lifestyle and fat-enriched dietary habits, WHR rather than body-mass-index emerged as a robust predictor of risk for T2D in this population.", "author" : [ { "dropping-particle" : "", "family" : "Gupta", "given" : "Vipin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khadgawat", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Hon Keung Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Satish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Ajay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Vadlamudi Raghavendra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sachdeva", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of human genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "361-8", "title" : "A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India.", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "91", "plainTextFormattedCitation" : "91", "previouslyFormattedCitation" : "91" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }91, none of the cases or controls included endogamous samples. An important consideration to external validity was the sub-structure of the included samples; a minority of the included datasets (6/31) were of Dravidian South Asians. There is some evidence of variation in risk allele frequencies and risk for complex diseases among Indo-Aryan and Dravidian groups, which may restrict the applicability of our findings to the latter group. A more thorough discussion of this population sub-structure is undertaken in the next section. In the EpiDREAM cohort, South Asians were largely sampled from South India (88%), including Hyderabad, Bangalore, and Chennai, representing a Dravidian population. Therefore, generalizability to Indo-Aryan groups may be limitedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajhg.2013.07.006", "ISSN" : "1537-6605", "PMID" : "23932107", "abstract" : "Most Indian groups descend from a mixture of two genetically divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians (ASI) not closely related to groups outside the subcontinent. The date of mixture is unknown but has implications for understanding Indian history. We report genome-wide data from 73 groups from the Indian subcontinent and analyze linkage disequilibrium to estimate ANI-ASI mixture dates ranging from about 1,900 to 4,200 years ago. In a subset of groups, 100% of the mixture is consistent with having occurred during this period. These results show that India experienced a demographic transformation several thousand years ago, from a region in which major population mixture was common to one in which mixture even between closely related groups became rare because of a shift to endogamy.", "author" : [ { "dropping-particle" : "", "family" : "Moorjani", "given" : "Priya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lipson", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Po-Ru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Govindaraj", "given" : "Periyasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Bonnie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "9", "5" ] ] }, "page" : "422-38", "title" : "Genetic evidence for recent population mixture in India.", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/nature08365", "ISSN" : "1476-4687", "PMID" : "19779445", "abstract" : "India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' (ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.", "author" : [ { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-2", "issue" : "7263", "issued" : { "date-parts" : [ [ "2009", "9", "24" ] ] }, "page" : "489-94", "title" : "Reconstructing Indian population history.", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "20,21", "plainTextFormattedCitation" : "20,21", "previouslyFormattedCitation" : "20,21" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20,21. White Caucasians, on the other hand, were sampled from Canada, United States, Europe, and Australia, making the results very generalizable. Lastly, the two birth cohorts used for the methylation analysis were drawn from Canadian cities and therefore the findings are likely to be generalizable to South Asian and white populations with similar social and economic groups.5.3 Other considerations for trans-ethnic genetic studies5.3.1 Population stratification Population stratification refers to systematic differences between sub-populations that arise from ancestryADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12520-2", "ISSN" : "0140-6736", "PMID" : "12598158", "abstract" : "Great efforts and expense have been expended in attempts to detect genetic polymorphisms contributing to susceptibility to complex human disease. Concomitantly, technology for detection and scoring of single nucleotide polymorphisms (SNPs) has undergone rapid development, extensive catalogues of SNPs across the genome have been constructed, and SNPs have been increasingly used as a means for investigation of the genetic causes of complex human diseases. For many diseases, population-based studies of unrelated individuals--in which case-control and cohort studies serve as standard designs for genetic association analysis--can be the most practical and powerful approach. However, extensive debate has arisen about optimum study design, and considerable concern has been expressed that these approaches are prone to population stratification, which can lead to biased or spurious results. Over the past decade, a great shift has been noted, away from case-control and cohort studies, towards family-based association designs. These designs have fewer problems with population stratification but have greater genotyping and sampling requirements, and data can be difficult or impossible to gather. We discuss past evidence for population stratification on genotype-phenotype association studies, review methods to detect and account for it, and present suggestions for future study design and analysis.", "author" : [ { "dropping-particle" : "", "family" : "Cardon", "given" : "Lon R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9357", "issued" : { "date-parts" : [ [ "2003", "3", "15" ] ] }, "language" : "English", "page" : "598-604", "publisher" : "Elsevier", "title" : "Population stratification and spurious allelic association.", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "226", "plainTextFormattedCitation" : "226", "previouslyFormattedCitation" : "226" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }226. These differences include frequency of risk alleles and variation in methylation irrespective of disease statusADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/gepi.21789", "ISSN" : "1098-2272", "PMID" : "24478250", "abstract" : "DNA methylation is an important epigenetic mechanism that has been linked to complex diseases and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome-wide association studies, issues such as population stratification will need to be addressed. It is well-documented that failure to adjust for population stratification can lead to false positives in genetic association studies, but population stratification is often unaccounted for in DNA methylation studies. Here, we propose several approaches to correct for population stratification using principal components (PCs) from different subsets of genome-wide methylation data. We first illustrate the potential for confounding due to population stratification by demonstrating widespread associations between DNA methylation and race in 388 individuals (365 African American and 23 Caucasian). We subsequently evaluate the performance of our PC-based approaches and other methods in adjusting for confounding due to population stratification. Our simulations show that (1) all of the methods considered are effective at removing inflation due to population stratification, and (2) maximum power can be obtained with single-nucleotide polymorphism (SNP)-based PCs, followed by methylation-based PCs, which outperform both surrogate variable analysis and genomic control. Among our different approaches to computing methylation-based PCs, we find that PCs based on CpG sites chosen for their potential to proxy nearby SNPs can provide a powerful and computationally efficient approach to adjust for population stratification in DNA methylation studies when genome-wide SNP data are unavailable.", "author" : [ { "dropping-particle" : "", "family" : "Barfield", "given" : "Richard T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almli", "given" : "Lynn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kilaru", "given" : "Varun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Alicia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mercer", "given" : "Kristina B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duncan", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klengel", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehta", "given" : "Divya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Binder", "given" : "Elisabeth B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Epstein", "given" : "Michael P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ressler", "given" : "Kerry J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Conneely", "given" : "Karen N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetic epidemiology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "4" ] ] }, "page" : "231-41", "title" : "Accounting for population stratification in DNA methylation studies.", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "227", "plainTextFormattedCitation" : "227", "previouslyFormattedCitation" : "227" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }227. Variation in allele frequencies attributable to diversity in population and unrelated to outcome status can lead to the detection of spurious associations. Notably, population stratification is the most commonly cited reason for non-replicationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12520-2", "ISSN" : "0140-6736", "PMID" : "12598158", "abstract" : "Great efforts and expense have been expended in attempts to detect genetic polymorphisms contributing to susceptibility to complex human disease. Concomitantly, technology for detection and scoring of single nucleotide polymorphisms (SNPs) has undergone rapid development, extensive catalogues of SNPs across the genome have been constructed, and SNPs have been increasingly used as a means for investigation of the genetic causes of complex human diseases. For many diseases, population-based studies of unrelated individuals--in which case-control and cohort studies serve as standard designs for genetic association analysis--can be the most practical and powerful approach. However, extensive debate has arisen about optimum study design, and considerable concern has been expressed that these approaches are prone to population stratification, which can lead to biased or spurious results. Over the past decade, a great shift has been noted, away from case-control and cohort studies, towards family-based association designs. These designs have fewer problems with population stratification but have greater genotyping and sampling requirements, and data can be difficult or impossible to gather. We discuss past evidence for population stratification on genotype-phenotype association studies, review methods to detect and account for it, and present suggestions for future study design and analysis.", "author" : [ { "dropping-particle" : "", "family" : "Cardon", "given" : "Lon R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9357", "issued" : { "date-parts" : [ [ "2003", "3", "15" ] ] }, "language" : "English", "page" : "598-604", "publisher" : "Elsevier", "title" : "Population stratification and spurious allelic association.", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "226", "plainTextFormattedCitation" : "226", "previouslyFormattedCitation" : "226" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }226. Association studies, in an attempt to avoid bias from population stratification, have used methods such as genomic control to correct for inflated test statistics and adjustment with principle components. The issue of population stratification also extends to methylation analyses, which show evidence of variation by ethnic / racial groupsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/bdra.20770", "ISSN" : "1542-0760", "PMID" : "21308978", "abstract" : "BACKGROUND: DNA methylation patterns differ among children and adults and play an unambiguous role in several disease processes, particularly cancers. The origin of these differences is inadequately understood, and this is a question of specific relevance to childhood and adult cancer.\n\nMETHODS: DNA methylation levels at 26,485 autosomal CpGs were assayed in 201 newborns (107 African American and 94 Caucasian). Nonparametric analyses were performed to examine the relation between these methylation levels and maternal parity, maternal age, newborn gestational age, newborn gender, and newborn race. To identify the possible influences of confounding, stratification was performed by a second and third variable. For genes containing CpGs with significant differences in DNA methylation levels between races, analyses were performed to identify highly represented gene ontological terms and functional pathways.\n\nRESULTS: 13.7% (3623) of the autosomal CpGs exhibited significantly different levels of DNA methylation between African Americans and Caucasians; 2% of autosomal CpGs had significantly different DNA methylation levels between male and female newborns. Cancer pathways, including four (pancreatic, prostate, bladder, and melanoma) with substantial differences in incidence between the races, were highly represented among the genes containing significant race-divergent CpGs.\n\nCONCLUSIONS: At birth, there are significantly different DNA methylation levels between African Americans and Caucasians at a subset of CpG dinucleotides. It is possible that some of the epigenetic precursors to cancer exist at birth and that these differences partially explain the different incidence rates of specific cancers between the races.", "author" : [ { "dropping-particle" : "", "family" : "Adkins", "given" : "Ronald M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krushkal", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tylavsky", "given" : "Frances A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomas", "given" : "Fridtjof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Birth defects research. Part A, Clinical and molecular teratology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2011", "8" ] ] }, "page" : "728-36", "title" : "Racial differences in gene-specific DNA methylation levels are present at birth.", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1101/gr.154187.112", "ISSN" : "1549-5469", "PMID" : "23908385", "abstract" : "DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites. The distinctly methylated genes identified suggest an influence of DNA methylation on phenotype differences, such as susceptibility to certain diseases and pathogens, and response to drugs and environmental agents. DNA methylation differences can be partially traced back to genetic variation, suggesting that differentially methylated CpG sites serve as evolutionarily established mediators between the genetic code and phenotypic variability. Notably, one-third of the DNA methylation differences were not associated with any genetic variation, suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels, highlighting the contribution of epigenetic modification to natural human variation.", "author" : [ { "dropping-particle" : "", "family" : "Heyn", "given" : "Holger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moran", "given" : "Sebastian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hernando-Herraez", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sayols", "given" : "Sergi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gomez", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandoval", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monk", "given" : "Dave", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hata", "given" : "Kenichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marques-Bonet", "given" : "Tomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Liewei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esteller", "given" : "Manel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genome research", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "1363-72", "title" : "DNA methylation contributes to natural human variation.", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "228,229", "plainTextFormattedCitation" : "228,229", "previouslyFormattedCitation" : "228,229" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }228,229. These differences could arise from epigenetic inheritanceADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/sj.ejhg.5201538", "ISSN" : "1018-4813", "PMID" : "16391557", "abstract" : "Transgenerational effects of maternal nutrition or other environmental 'exposures' are well recognised, but the possibility of exposure in the male influencing development and health in the next generation(s) is rarely considered. However, historical associations of longevity with paternal ancestors' food supply in the slow growth period (SGP) in mid childhood have been reported. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we identified 166 fathers who reported starting smoking before age 11 years and compared the growth of their offspring with those with a later paternal onset of smoking, after correcting for confounders. We analysed food supply effects on offspring and grandchild mortality risk ratios (RR) using 303 probands and their 1818 parents and grandparents from the 1890, 1905 and 1920 Overkalix cohorts, northern Sweden. After appropriate adjustment, early paternal smoking is associated with greater body mass index (BMI) at 9 years in sons, but not daughters. Sex-specific effects were also shown in the Overkalix data; paternal grandfather's food supply was only linked to the mortality RR of grandsons, while paternal grandmother's food supply was only associated with the granddaughters' mortality RR. These transgenerational effects were observed with exposure during the SGP (both grandparents) or fetal/infant life (grandmothers) but not during either grandparent's puberty. We conclude that sex-specific, male-line transgenerational responses exist in humans and hypothesise that these transmissions are mediated by the sex chromosomes, X and Y. Such responses add an entirely new dimension to the study of gene-environment interactions in development and health.", "author" : [ { "dropping-particle" : "", "family" : "Pembrey", "given" : "Marcus E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bygren", "given" : "Lars Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaati", "given" : "Gunnar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Edvinsson", "given" : "S\u00f6ren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Northstone", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sj\u00f6str\u00f6m", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golding", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of human genetics : EJHG", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "2", "14" ] ] }, "page" : "159-66", "title" : "Sex-specific, male-line transgenerational responses in humans.", "title-short" : "Eur J Hum Genet", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "230", "plainTextFormattedCitation" : "230", "previouslyFormattedCitation" : "230" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }230, differences in environmental factors by population, and allele-specific DNA methylation, which is affected by variation in allele frequenciesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/gb-2011-12-1-r10", "ISSN" : "1465-6914", "PMID" : "21251332", "abstract" : "BACKGROUND: DNA methylation is an essential epigenetic mechanism involved in gene regulation and disease, but little is known about the mechanisms underlying inter-individual variation in methylation profiles. Here we measured methylation levels at 22,290 CpG dinucleotides in lymphoblastoid cell lines from 77 HapMap Yoruba individuals, for which genome-wide gene expression and genotype data were also available.\n\nRESULTS: Association analyses of methylation levels with more than three million common single nucleotide polymorphisms (SNPs) identified 180 CpG-sites in 173 genes that were associated with nearby SNPs (putatively in cis, usually within 5 kb) at a false discovery rate of 10%. The most intriguing trans signal was obtained for SNP rs10876043 in the disco-interacting protein 2 homolog B gene (DIP2B, previously postulated to play a role in DNA methylation), that had a genome-wide significant association with the first principal component of patterns of methylation; however, we found only modest signal of trans-acting associations overall. As expected, we found significant negative correlations between promoter methylation and gene expression levels measured by RNA-sequencing across genes. Finally, there was a significant overlap of SNPs that were associated with both methylation and gene expression levels.\n\nCONCLUSIONS: Our results demonstrate a strong genetic component to inter-individual variation in DNA methylation profiles. Furthermore, there was an enrichment of SNPs that affect both methylation and gene expression, providing evidence for shared mechanisms in a fraction of genes.", "author" : [ { "dropping-particle" : "", "family" : "Bell", "given" : "Jordana T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pai", "given" : "Athma A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pickrell", "given" : "Joseph K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaffney", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pique-Regi", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Degner", "given" : "Jacob F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilad", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pritchard", "given" : "Jonathan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genome biology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "R10", "title" : "DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.174", "ISSN" : "1546-1718", "PMID" : "18568024", "abstract" : "Allele-specific DNA methylation (ASM) is a hallmark of imprinted genes, but ASM in the larger nonimprinted fraction of the genome is less well characterized. Using methylation-sensitive SNP analysis (MSNP), we surveyed the human genome at 50K and 250K resolution, identifying ASM as recurrent genotype call conversions from heterozygosity to homozygosity when genomic DNAs were predigested with the methylation-sensitive restriction enzyme HpaII. Using independent assays, we confirmed ASM at 16 SNP-tagged loci distributed across various chromosomes. At 12 of these loci (75%), the ASM tracked strongly with the sequence of adjacent SNPs. Further analysis showed allele-specific mRNA expression at two loci from this methylation-based screen--the vanin and CYP2A6-CYP2A7 gene clusters--both implicated in traits of medical importance. This recurrent phenomenon of sequence-dependent ASM has practical implications for mapping and interpreting associations of noncoding SNPs and haplotypes with human phenotypes.", "author" : [ { "dropping-particle" : "", "family" : "Kerkel", "given" : "Kristi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spadola", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yuan", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kosek", "given" : "Jolanta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jiang", "given" : "Le", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hod", "given" : "Eldad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Kerry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Murty", "given" : "Vundavalli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schupf", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilain", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Mitzi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haghighi", "given" : "Fatemeh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tycko", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2008", "7" ] ] }, "page" : "904-8", "title" : "Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation.", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.ajhg.2010.01.014", "ISSN" : "1537-6605", "PMID" : "20159110", "abstract" : "DNA methylation is assumed to be complementary on both alleles across the genome, although there are exceptions, notably in regions subject to genomic imprinting. We present a genome-wide survey of the degree of allelic skewing of DNA methylation with the aim of identifying previously unreported differentially methylated regions (DMRs) associated primarily with genomic imprinting or DNA sequence variation acting in cis. We used SNP microarrays to quantitatively assess allele-specific DNA methylation (ASM) in amplicons covering 7.6% of the human genome following cleavage with a cocktail of methylation-sensitive restriction enzymes (MSREs). Selected findings were verified using bisulfite-mapping and gene-expression analyses, subsequently tested in a second tissue from the same individuals, and replicated in DNA obtained from 30 parent-child trios. Our approach detected clear examples of ASM in the vicinity of known imprinted loci, highlighting the validity of the method. In total, 2,704 (1.5%) of our 183,605 informative and stringently filtered SNPs demonstrate an average relative allele score (RAS) change > or =0.10 following MSRE digestion. In agreement with previous reports, the majority of ASM ( approximately 90%) appears to be cis in nature, and several examples of tissue-specific ASM were identified. Our data show that ASM is a widespread phenomenon, with >35,000 such sites potentially occurring across the genome, and that a spectrum of ASM is likely, with heterogeneity between individuals and across tissues. These findings impact our understanding about the origin of individual phenotypic differences and have implications for genetic studies of complex disease.", "author" : [ { "dropping-particle" : "", "family" : "Schalkwyk", "given" : "Leonard C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meaburn", "given" : "Emma L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dempster", "given" : "Emma L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jeffries", "given" : "Aaron R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mill", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "2", "12" ] ] }, "page" : "196-212", "title" : "Allelic skewing of DNA methylation is widespread across the genome.", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "190,231,232", "plainTextFormattedCitation" : "190,231,232", "previouslyFormattedCitation" : "190,231,232" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }190,231,232. The literature supports a North-South gradient amongst South Asians, reflecting a historic admixture between Indo-Aryan and Dravidian people; Indo-Aryans tend to be more closely related to white CaucasiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ajhg.2013.07.006", "ISSN" : "1537-6605", "PMID" : "23932107", "abstract" : "Most Indian groups descend from a mixture of two genetically divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians (ASI) not closely related to groups outside the subcontinent. The date of mixture is unknown but has implications for understanding Indian history. We report genome-wide data from 73 groups from the Indian subcontinent and analyze linkage disequilibrium to estimate ANI-ASI mixture dates ranging from about 1,900 to 4,200 years ago. In a subset of groups, 100% of the mixture is consistent with having occurred during this period. These results show that India experienced a demographic transformation several thousand years ago, from a region in which major population mixture was common to one in which mixture even between closely related groups became rare because of a shift to endogamy.", "author" : [ { "dropping-particle" : "", "family" : "Moorjani", "given" : "Priya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lipson", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Po-Ru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Govindaraj", "given" : "Periyasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Bonnie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "9", "5" ] ] }, "page" : "422-38", "title" : "Genetic evidence for recent population mixture in India.", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0102645", "ISSN" : "1932-6203", "PMID" : "25115870", "abstract" : "The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.", "author" : [ { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Turro", "given" : "Ernest", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "William R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "Sian-Tsung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afzal", "given" : "Uzma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Afaq", "given" : "Saima", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehne", "given" : "Benjamin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Reilly", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaulton", "given" : "Kyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearson", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lavery", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vandrovcova", "given" : "Jana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wass", "given" : "Mark N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Kathryn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oozageer", "given" : "Laticia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Ishminder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Al-Hussaini", "given" : "Abtehale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mills", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grewal", "given" : "Jagvir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Panoulas", "given" : "Vasileios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewin", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Northwood", "given" : "Korrinne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geoghegan", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Yingrui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aitman", "given" : "Timothy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butcher", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2014", "1", "12" ] ] }, "page" : "e102645", "title" : "The South Asian genome.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/nature08365", "ISSN" : "1476-4687", "PMID" : "19779445", "abstract" : "India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' (ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.", "author" : [ { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-3", "issue" : "7263", "issued" : { "date-parts" : [ [ "2009", "9", "24" ] ] }, "page" : "489-94", "title" : "Reconstructing Indian population history.", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "20,21,108", "plainTextFormattedCitation" : "20,21,108", "previouslyFormattedCitation" : "20,21,108" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20,21,108. Additionally, as South Asian populations are endogamous, genetic stratification is marked and alleles of rarer variants may be observed with a higher frequency in this group compared to groups with greater gene flowADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1747-0862", "PMID" : "19565013", "abstract" : "Population stratification and its influence on genetic association studies is a controversial topic. Although it has been suggested that stratification is unlikely to bias the results of association studies conducted in developed countries, convincing contrary empirical evidence has been published. However, it is in populations where historical ethnic, religious and language barriers exist that community subdivisions will predictably exert greatest genetic effect, and influence the organization of association studies. In many of the populations of the Indian sub-continent, these basic population divisions are compounded by a strict tradition of intra-community marriage and by marriage between close biological relatives. Data on the very significant levels of genetic diversity that characterize the populations of India and Pakistan, with some 50,000-60,000 caste and non-caste communities in India, and average first cousin marriage rates of 40%-50% in Pakistan, are presented and discussed. Under these circumstances, failure to explicitly control for caste/biraderi membership and the presence of consanguinity could seriously jeopardize, and may totally invalidate, the results of association/case control studies and clinical trials.", "author" : [ { "dropping-particle" : "", "family" : "Bittles", "given" : "Alan H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of molecular and genetic medicine : an international journal of biomedical research", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2005", "1" ] ] }, "page" : "43-8", "title" : "Population stratification and genetic association studies in South Asia.", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "233", "plainTextFormattedCitation" : "233", "previouslyFormattedCitation" : "233" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }233, such as many white Caucasian populations. These make considerations of population stratification particularly important in this group. Subgroups within white Caucasians also existADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2119/molmed.2009.00094", "ISSN" : "1528-3658", "PMID" : "19707526", "abstract" : "The definition of European population genetic substructure and its application to understanding complex phenotypes is becoming increasingly important. In the current study using over 4,000 subjects genotyped for 300,000 single-nucleotide polymorphisms (SNPs), we provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs) for application in genetic studies. In general, the graphical description of these principal components analyses (PCA) of diverse European subjects showed a strong correspondence to the geographical relationships of specific countries or regions of origin. Clearer separation of different ethnic and regional populations was observed when northern and southern European groups were considered separately and the PCA results were influenced by the inclusion or exclusion of different self-identified population groups including Ashkenazi Jewish, Sardinian, and Orcadian ethnic groups. SNP AIM sets were identified that could distinguish the regional and ethnic population groups. Moreover, the studies demonstrated that most allele frequency differences between different European groups could be controlled effectively in analyses using these AIM sets. The European substructure AIMs should be widely applicable to ongoing studies to confirm and delineate specific disease susceptibility candidate regions without the necessity of performing additional genome-wide SNP studies in additional subject sets.", "author" : [ { "dropping-particle" : "", "family" : "Tian", "given" : "Chao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kosoy", "given" : "Roman", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nassir", "given" : "Rami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Villoslada", "given" : "Pablo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klareskog", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammarstr\u00f6m", "given" : "Lennart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garchon", "given" : "Henri-Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pulver", "given" : "Ann E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ransom", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gregersen", "given" : "Peter K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seldin", "given" : "Michael F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular medicine (Cambridge, Mass.)", "id" : "ITEM-1", "issue" : "11-12", "issued" : { "date-parts" : [ [ "0", "1" ] ] }, "page" : "371-83", "title" : "European population genetic substructure: further definition of ancestry informative markers for distinguishing among diverse European ethnic groups.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "19", "plainTextFormattedCitation" : "19", "previouslyFormattedCitation" : "19" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }19, though there is less evidence of genetic stratification as a result of consanguineous and endogamous unions. We did not find evidence of population substructure within the ethnic groups in our cohort and therefore the analyses were not adjusted for population stratification. 5.3.2 Linkage disequilibrium The non-random association of alleles at two or more loci, formally known as linkage disequilibrium, is an important concept when studying ethnically diverse populations. Linkage equilibrium implies statistical independence, such that frequency of an AB haplotype is the product of allele frequencies pA and pBADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrg2361", "ISSN" : "1471-0064", "PMID" : "18427557", "abstract" : "Linkage disequilibrium--the nonrandom association of alleles at different loci--is a sensitive indicator of the population genetic forces that structure a genome. Because of the explosive growth of methods for assessing genetic variation at a fine scale, evolutionary biologists and human geneticists are increasingly exploiting linkage disequilibrium in order to understand past evolutionary and demographic events, to map genes that are associated with quantitative characters and inherited diseases, and to understand the joint evolution of linked sets of genes. This article introduces linkage disequilibrium, reviews the population genetic processes that affect it and describes some of its uses. At present, linkage disequilibrium is used much more extensively in the study of humans than in non-humans, but that is changing as technological advances make extensive genomic studies feasible in other species.", "author" : [ { "dropping-particle" : "", "family" : "Slatkin", "given" : "Montgomery", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Genetics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2008", "6" ] ] }, "page" : "477-85", "title" : "Linkage disequilibrium--understanding the evolutionary past and mapping the medical future.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "234", "plainTextFormattedCitation" : "234", "previouslyFormattedCitation" : "234" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }234. Population genetic forces, such as selection, polymorphism, genetic drift, and gene flow will create LD. Among humans, haplotype blocks vary; they tend to be shortest in African populations and larger in CaucasiansADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrg1123", "ISSN" : "1471-0056", "PMID" : "12897771", "abstract" : "There is great interest in the patterns and extent of linkage disequilibrium (LD) in humans and other species. Characterizing LD is of central importance for gene-mapping studies and can provide insights into the biology of recombination and human demographic history. Here, we review recent developments in this field, including the recently proposed 'haplotype-block' model of LD. We describe some of the recent data in detail and compare the observed patterns to those seen in simulations.", "author" : [ { "dropping-particle" : "", "family" : "Wall", "given" : "Jeffrey D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pritchard", "given" : "Jonathan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Genetics", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2003", "8" ] ] }, "page" : "587-97", "title" : "Haplotype blocks and linkage disequilibrium in the human genome.", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "235", "plainTextFormattedCitation" : "235", "previouslyFormattedCitation" : "235" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }235. Deviations from equilibrium can be partitioned into average disequilibrium within sub-populations and differences in allele frequencies between sub-populations. The latter is commonly studied using Wright’s fixation index (FST)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrg2361", "ISSN" : "1471-0064", "PMID" : "18427557", "abstract" : "Linkage disequilibrium--the nonrandom association of alleles at different loci--is a sensitive indicator of the population genetic forces that structure a genome. Because of the explosive growth of methods for assessing genetic variation at a fine scale, evolutionary biologists and human geneticists are increasingly exploiting linkage disequilibrium in order to understand past evolutionary and demographic events, to map genes that are associated with quantitative characters and inherited diseases, and to understand the joint evolution of linked sets of genes. This article introduces linkage disequilibrium, reviews the population genetic processes that affect it and describes some of its uses. At present, linkage disequilibrium is used much more extensively in the study of humans than in non-humans, but that is changing as technological advances make extensive genomic studies feasible in other species.", "author" : [ { "dropping-particle" : "", "family" : "Slatkin", "given" : "Montgomery", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature reviews. Genetics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2008", "6" ] ] }, "page" : "477-85", "title" : "Linkage disequilibrium--understanding the evolutionary past and mapping the medical future.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "234", "plainTextFormattedCitation" : "234", "previouslyFormattedCitation" : "234" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }234. A recent study of the South Asian genome revealed that while a majority of genetic variants is universally shared, substantial heterogeneity in allele frequency exists between populations. Notably, the mean FST between South Asians and white Caucasians showed the greatest stratification (FST = 0.010) compared to other ethnic groups. Loci showing the greatest heterogeneity were enriched for genes involved in metabolism. Additionally, the authors report discovery of SNPs unique to South Asians, again mostly involved in lipid and carbohydrate metabolism. This discovery is congruent with our report of associations of 7 SNPs on AP3S2, ST6GAL1, C6orf57, GRB14, HNF4α, VPS26A, and TMEM163d with type 2 diabetes in South Asians, but not Caucasians, a pattern that has been shown for other traitsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s100380200016", "ISSN" : "1434-5161", "PMID" : "11950066", "abstract" : "Sequence variation in the human genome has been used as a tool in studying human diseases and the evolutionary history of man. A human inherited predisposition to tuberculosis has been suggested and studied; however. genetic mechanisms are still ambiguous. In the present study, we scanned the regulatory and coding region of Nuclear LIM Interactor-Interacting Factor gene (NLI-IF), which is physically close to the tuberculosis-associated gene NRAMP1. Thirteen biallelic single-nucleotide polymorphisms (SNPs) were identified from four ethnic populations (African-American, Caucasian, Hispanic, and Asian) with population-specific distribution of alleles. The extent of linkage disequilibrium (LD) between 402T > C, and 472-42G > A varied distinctly from complete LD in the non-African-American groups to strong but incomplete LD in African-Americans. Both SNPs were in significant LD with the polymorphism 3' UTR in NRAMP1 among these ethnic groups (P < 0.02), except 402T > C in African-Americans. In a case-control study with a Caucasian population, three cosmopolitan SNPs (204C > A, 402T > C and 472 - 42G > A) in NLI-IF showed no significant association with human susceptibility to tuberculosis. Our results support the \"out-of-Africa\" model of human origin, and suggest the time for the common ancestor dispersing from Africa could not have been more than approximately 385,620 years ago.", "author" : [ { "dropping-particle" : "", "family" : "Ma", "given" : "Xin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dou", "given" : "Shujun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olsen", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teeter", "given" : "Larry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adams", "given" : "Gerald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graviss", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2002", "1" ] ] }, "page" : "140-5", "title" : "Ethnic divergence and linkage disequilibrium of novel SNPs in the human NLI-IF gene: evidence of human origin and lack of association with tuberculosis susceptibility.", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "236", "plainTextFormattedCitation" : "236", "previouslyFormattedCitation" : "236" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }236. Fine mapping analyses of these SNPs may reveal causal variants tagged by the above unique to South Asians as a result of varying LD. Furthermore, future such investigations may reveal more genetic variants contributing to cardio-metabolic phenotypes that together can explain the divergent risk in this group.5.4 Future directions and ConclusionsOverall, our results indicate that the greater risk for metabolic traits in South Asians likely does not result from shared genetic variants, but those unique to South Asians. Evidence for this comes from our meta-analysis (Chapter 2) and genome-wide study of DNA methylation (Chapter 4). Furthermore, there is evidence for differences in interaction of an underlying genetic risk with other physiological traits, notably fat storage, which also contributes to this ethnic variation (Chapter 3). Future studies should: 1) conduct large-scale genome-wide investigations of SNPs and methylation loci implicated in metabolic traits, 2) focus on fine-mapping already identified variants showing heterogeneity in effect between South Asians and white Caucasians, 3) homozygocity mapping in consanguineous South Asian familiesADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nature08365", "ISSN" : "1476-4687", "PMID" : "19779445", "abstract" : "India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' (ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.", "author" : [ { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Alkes L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature", "id" : "ITEM-1", "issue" : "7263", "issued" : { "date-parts" : [ [ "2009", "9", "24" ] ] }, "page" : "489-94", "title" : "Reconstructing Indian population history.", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ajhg.2013.07.006", "ISSN" : "1537-6605", "PMID" : "23932107", "abstract" : "Most Indian groups descend from a mixture of two genetically divergent populations: Ancestral North Indians (ANI) related to Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians (ASI) not closely related to groups outside the subcontinent. The date of mixture is unknown but has implications for understanding Indian history. We report genome-wide data from 73 groups from the Indian subcontinent and analyze linkage disequilibrium to estimate ANI-ASI mixture dates ranging from about 1,900 to 4,200 years ago. In a subset of groups, 100% of the mixture is consistent with having occurred during this period. These results show that India experienced a demographic transformation several thousand years ago, from a region in which major population mixture was common to one in which mixture even between closely related groups became rare because of a shift to endogamy.", "author" : [ { "dropping-particle" : "", "family" : "Moorjani", "given" : "Priya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thangaraj", "given" : "Kumarasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patterson", "given" : "Nick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lipson", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loh", "given" : "Po-Ru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Govindaraj", "given" : "Periyasamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berger", "given" : "Bonnie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reich", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Lalji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "9", "5" ] ] }, "page" : "422-38", "title" : "Genetic evidence for recent population mixture in India.", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "20,21", "plainTextFormattedCitation" : "20,21", "previouslyFormattedCitation" : "20,21" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }20,21, and 4) study differences in gene-gene and gene-environment interactions which may explain differential risk from some genetic variants.ReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. World Health Organization. Global status report on noncommunicable diseases 2014. Geneva, Switzerland; 2012.2. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 365(9467):1333–46. doi:10.1016/S0140-6736(05)61032-X.3. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia. 2003;46(1):3–19. doi:10.1007/s00125-002-1009-0.4. Weyer C, Tataranni PA, Bogardus C, Pratley RE. Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development. Diabetes Care. 2001;24(1):89–94. Available at: . Accessed March 13, 2014.5. Elbein SC, Hasstedt SJ, Wegner K, Kahn SE. Heritability of pancreatic beta-cell function among nondiabetic members of Caucasian familial type 2 diabetic kindreds. J Clin Endocrinol Metab. 1999;84(4):1398–403. doi:10.1210/jcem.84.4.5604.6. Schousboe K, Visscher PM, Henriksen JE, Hopper JL, S?rensen TIA, Kyvik KO. Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion. Diabetologia. 2003;46(9):1276–83. doi:10.1007/s00125-003-1165-x.7. Katoh S, Lehtovirta M, Kaprio J, et al. Genetic and environmental effects on fasting and postchallenge plasma glucose and serum insulin values in Finnish twins. J Clin Endocrinol Metab. 2005;90(5):2642–7. doi:10.1210/jc.2004-2471.8. Scott RA, Lagou V, Welch RP, et al. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012;44(9):991–1005. doi:10.1038/ng.2385.9. Manning AK, Hivert M-F, Scott RA, et al. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet. 2012;44(6):659–69. doi:10.1038/ng.2274.10. Dupuis J, Langenberg C, Prokopenko I, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010;42(2):105–16. doi:10.1038/ng.520.11. Saxena R, Hivert M-F, Langenberg C, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42(2):142–8. doi:10.1038/ng.521.12. Visscher PM, Brown MA, McCarthy MI, Yang J. Five years of GWAS discovery. Am J Hum Genet. 2012;90(1):7–24. doi:10.1016/j.ajhg.2011.11.029.13. Stahl EA, Wegmann D, Trynka G, et al. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat Genet. 2012;44(5):483–9. doi:10.1038/ng.2232.14. Maher B. Personal genomes: The case of the missing heritability. Nature. 2008;456(7218):18–21. doi:10.1038/456018a.15. Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–53. doi:10.1038/nature08494.16. Anand SS, Yusuf S, Vuksan V, et al. Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE). Lancet. 2000;356(9226):279–284. doi:10.1016/S0140-6736(00)02502-2.17. Rana A, de Souza RJ, Kandasamy S, Lear SA, Anand SS. Cardiovascular risk among South Asians living in Canada: a systematic review and meta-analysis. C open. 2014;2(3):E183–91. doi:10.9778/cmajo.20130064.18. Valera B, Sohani ZN, Rana A, Poirier P, Anand SS. The ethno-epidemiology of obesity. Can J Cardiol. 2014. doi:10.1016/j.cjca.2014.10.005.19. Tian C, Kosoy R, Nassir R, et al. European population genetic substructure: further definition of ancestry informative markers for distinguishing among diverse European ethnic groups. Mol Med. 15(11-12):371–83. doi:10.2119/molmed.2009.00094.20. Reich D, Thangaraj K, Patterson N, Price AL, Singh L. Reconstructing Indian population history. Nature. 2009;461(7263):489–94. doi:10.1038/nature08365.21. Moorjani P, Thangaraj K, Patterson N, et al. Genetic evidence for recent population mixture in India. Am J Hum Genet. 2013;93(3):422–38. doi:10.1016/j.ajhg.2013.07.006.22. Barnett AH, Dixon AN, Bellary S, et al. Type 2 diabetes and cardiovascular risk in the UK south Asian community. Diabetologia. 2006;49(10):2234–46. doi:10.1007/s00125-006-0325-1.23. Yusuf S, Reddy S, Ounpuu S, Anand S. Global Burden of Cardiovascular Diseases: Part I: General Considerations, the Epidemiologic Transition, Risk Factors, and Impact of Urbanization. Circulation. 2001;104(22):2746–2753. doi:10.1161/hc4601.099487.24. Yusuf S, Reddy S, Ounpuu S, Anand S. Global Burden of Cardiovascular Diseases: Part II: Variations in Cardiovascular Disease by Specific Ethnic Groups and Geographic Regions and Prevention Strategies. Circulation. 2001;104(23):2855–2864. doi:10.1161/hc4701.099488.25. Mather HM, Chaturvedi N, Fuller JH. Mortality and morbidity from diabetes in South Asians and Europeans: 11-year follow-up of the Southall Diabetes Survey, London, UK. Diabet Med. 1998;15(1):53–9. doi:10.1002/(SICI)1096-9136(199801)15:1<53::AID-DIA521>3.0.CO;2-V.26. Tillin T, Forouhi N, Johnston DG, McKeigue PM, Chaturvedi N, Godsland IF. Metabolic syndrome and coronary heart disease in South Asians, African-Caribbeans and white Europeans: a UK population-based cross-sectional study. Diabetologia. 2005;48(4):649–56. doi:10.1007/s00125-005-1689-3.27. Prasad DS, Kabir Z, Dash AK, Das BC. Prevalence and risk factors for metabolic syndrome in Asian Indians: A community study from urban Eastern India. J Cardiovasc Dis Res. 2012;3(3):204–11. doi:10.4103/0975-3583.98895.28. Mohan V, Shanthirani S, Deepa R, Premalatha G, Sastry NG, Saroja R. Intra-urban differences in the prevalence of the metabolic syndrome in southern India - the Chennai Urban Population Study (CUPS No. 4). Diabet Med. 2001;18(4):280–287. doi:10.1046/j.1464-5491.2001.00421.x.29. Deepa M, Farooq S, Datta M, Deepa R, Mohan V. Prevalence of metabolic syndrome using WHO, ATPIII and IDF definitions in Asian Indians: the Chennai Urban Rural Epidemiology Study (CURES-34). Diabetes Metab Res Rev. 2007;23(2):127–34. doi:10.1002/dmrr.658.30. Petersen KF, Dufour S, Feng J, et al. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc Natl Acad Sci U S A. 2006;103(48):18273–7. doi:10.1073/pnas.0608537103.31. Raji A, Seely EW, Arky RA, Simonson DC. Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab. 2001;86(11):5366–71. doi:10.1210/jcem.86.11.7992.32. Ikehara S, Tabák AG, Akbaraly TN, et al. Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study. Diabetologia. 2015;58(3):534–42. doi:10.1007/s00125-014-3448-9.33. Sniderman AD, Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A. Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis. Int J Epidemiol. 2007;36(1):220–5. doi:10.1093/ije/dyl245.34. Gujral UP, Pradeepa R, Weber MB, Narayan KMV, Mohan V. Type 2 diabetes in South Asians: similarities and differences with white Caucasian and other populations. Ann N Y Acad Sci. 2013;1281:51–63. doi:10.1111/j.1749-6632.2012.06838.x.35. Yajnik CS, Yudkin JS. The Y-Y paradox. Lancet. 2004;363(9403):163. doi:10.1016/S0140-6736(03)15269-5.36. Banerji MA, Faridi N, Atluri R, Chaiken RL, Lebovitz HE. Body Composition, Visceral Fat, Leptin, and Insulin Resistance in Asian Indian Men1. J Clin Endocrinol Metab. 2013. Available at: . Accessed January 26, 2015.37. Chandalia M, Lin P, Seenivasan T, et al. Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men. Maedler K, ed. PLoS One. 2007;2(8):e812. doi:10.1371/journal.pone.0000812.38. Deurenberg P, Deurenberg-Yap M, Guricci S. Asians are different from Caucasians and from each other in their body mass index/body fat per cent relationship. Obes Rev. 2002;3(3):141–146. doi:10.1046/j.1467-789X.2002.00065.x.39. Anand SS, Tarnopolsky MA, Rashid S, et al. Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE). Stanojevic S, ed. PLoS One. 2011;6(7):e22112. doi:10.1371/journal.pone.0022112.40. Kohli S, Sniderman AD, Tchernof A, Lear SA. Ethnic-specific differences in abdominal subcutaneous adipose tissue compartments. Obesity (Silver Spring). 2010;18(11):2177–83. doi:10.1038/oby.2010.94.41. Balakrishnan P, Grundy SM, Islam A, Dunn F, Vega GL. Influence of upper and lower body adipose tissue on insulin sensitivity in South Asian men. J Investig Med. 2012;60(7):999–1004. doi:10.231/JIM.0b013e3182650a09.42. Leon DA, Moser KA. Low birth weight persists in South Asian babies born in England and Wales regardless of maternal country of birth. Slow pace of acculturation, physiological constraint or both? Analysis of routine data. J Epidemiol Community Health. 2012;66(6):544–51. doi:10.1136/jech.2010.112516.43. Margetts BM, Mohd Yusof S, Al Dallal Z, Jackson AA. Persistence of lower birth weight in second generation South Asian babies born in the United Kingdom. J Epidemiol Community Health. 2002;56(9):684–7. Available at: . Accessed May 20, 2014.44. Janssen PA, Thiessen P, Klein MC, Whitfield MF, Macnab YC, Cullis-Kuhl SC. Standards for the measurement of birth weight, length and head circumference at term in neonates of European, Chinese and South Asian ancestry. Open Med. 2007;1(2):e74–88. Available at: . Accessed April 20, 2015.45. Whincup PH, Gilg JA, Owen CG, Odoki K, Alberti KGMM, Cook DG. British South Asians aged 13-16 years have higher fasting glucose and insulin levels than Europeans. Diabet Med. 2005;22(9):1275–7. doi:10.1111/j.1464-5491.2005.01587.x.46. Rosenbaum M, Fennoy I, Accacha S, et al. Racial/ethnic differences in clinical and biochemical type 2 diabetes mellitus risk factors in children. Obesity (Silver Spring). 2013;21(10):2081–90. doi:10.1002/oby.20483.47. Ranjani H, Sonya J, Anjana RM, Mohan V. Prevalence of glucose intolerance among children and adolescents in urban South India (ORANGE-2). Diabetes Technol Ther. 2013;15(1):13–9. doi:10.1089/dia.2012.0236.48. Shaw NJ, Crabtree NJ, Kibirige MS, Fordham JN. Ethnic and gender differences in body fat in British schoolchildren as measured by DXA. Arch Dis Child. 2007;92(10):872–5. doi:10.1136/adc.2007.117911.49. Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med. 2002;346(11):802–10. doi:10.1056/NEJMoa012578.50. Wiegand S, Maikowski U, Blankenstein O, Biebermann H, Tarnow P, Gruters A. Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity -- a problem that is no longer restricted to minority groups. Eur J Endocrinol. 2004;151(2):199–206. doi:10.1530/eje.0.1510199.51. Peters J, Ulijaszek SJ. Population and sex differences in arm circumference and skinfold thicknesses among Indo-Pakistani children living in the East Midlands of Britain. Ann Hum Biol. 19(1):17–22. Available at: . Accessed April 27, 2015.52. Gulliford MC, Mahabir D, Rocke B, Chinn S, Rona R. Overweight, obesity and skinfold thicknesses of children of African or Indian descent in Trinidad and Tobago. Int J Epidemiol. 2001;30(5):989–98. Available at: . Accessed April 27, 2015.53. Stanfield KM, Wells JC, Fewtrell MS, Frost C, Leon DA. Differences in body composition between infants of South Asian and European ancestry: the London Mother and Baby Study. Int J Epidemiol. 2012;41(5):1409–18. doi:10.1093/ije/dys139.54. Modi N, Thomas EL, Uthaya SN, Umranikar S, Bell JD, Yajnik C. Whole Body Magnetic Resonance Imaging of Healthy Newborn Infants Demonstrates Increased Central Adiposity in Asian Indians. Pediatr Res. 2009;65(5):584–587. doi:10.1203/PDR.0b013e31819d98be.55. Yajnik CS, Lubree HG, Rege SS, et al. Adiposity and Hyperinsulinemia in Indians Are Present at Birth. J Clin Endocrinol Metab. 2002;87(12):5575–5580. doi:10.1210/jc.2002-020434.56. Nightingale CM, Rudnicka AR, Owen CG, Cook DG, Whincup PH. Patterns of body size and adiposity among UK children of South Asian, black African-Caribbean and white European origin: Child Heart And health Study in England (CHASE Study). Int J Epidemiol. 2011;40(1):33–44. doi:10.1093/ije/dyq180.57. Ramachandran P. Nutrition and child survival in India. Indian J Pediatr. 2010;77(3):301–5. doi:10.1007/s12098-010-0038-9.58. Brancati FL, Whelton PK, Kuller LH, Klag MJ. Diabetes mellitus, race, and socioeconomic status. A population-based study. Ann Epidemiol. 1996;6(1):67–73. Available at: . Accessed May 16, 2015.59. Young BA, Maynard C, Boyko EJ. Racial Differences in Diabetic Nephropathy, Cardiovascular Disease, and Mortality in a National Population of Veterans. Diabetes Care. 2003;26(8):2392–2399. doi:10.2337/diacare.26.8.2392.60. Carter JS, Pugh JA, Monterrosa A. Non-insulin-dependent diabetes mellitus in minorities in the United States. Ann Intern Med. 1996;125(3):221–32. Available at: . Accessed April 19, 2015.61. Gerstein HC, Waltman L. Why don’t pigs get diabetes? Explanations for variations in diabetes susceptibility in human populations living in a diabetogenic environment. CMAJ. 2006;174(1):25–6. doi:10.1503/cmaj.050649.62. Anand SS, Meyre D, Pare G, et al. Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study. Diabetes Care. 2013;36(9):2836–42. doi:10.2337/dc12-2553.63. Anand SS, Vasudevan A, Gupta M, et al. Rationale and design of South Asian Birth Cohort (START): a Canada-India collaborative study. BMC Public Health. 2013;13:79. doi:10.1186/1471-2458-13-79.64. Radha V, Mohan V. Genetic predisposition to type 2 diabetes among Asian Indians. Indian J Med Res. 2007;125(3):259–74. Available at: . Accessed February 8, 2014.65. Kanaya AM, Wassel CL, Mathur D, et al. Prevalence and correlates of diabetes in South asian indians in the United States: findings from the metabolic syndrome and atherosclerosis in South asians living in america study and the multi-ethnic study of atherosclerosis. Metab Syndr Relat Disord. 2010;8(2):157–64. doi:10.1089/met.2009.0062.66. Little J, Higgins JPT, Ioannidis JPA, et al. STrengthening the REporting of Genetic Association Studies (STREGA): an extension of the STROBE statement. PLoS Med. 2009;6(2):e22. doi:10.1371/journal.pmed.1000022.67. Lewis CM, Knight J. Introduction to genetic association studies. Cold Spring Harb Protoc. 2012;2012(3):297–306. doi:10.1101/068163.68. Johnson AD, Handsaker RE, Pulit SL, Nizzari MM, O’Donnell CJ, de Bakker PIW. SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics. 2008;24(24):2938–9. doi:10.1093/bioinformatics/btn564.69. Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods. 2006;11(2):193–206. doi:10.1037/1082-989X.11.2.193.70. Morris AP, Voight BF, Teslovich TM, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012;44(9):981–90. doi:10.1038/ng.2383.71. Kooner JS, Saleheen D, Sim X, et al. Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat Genet. 2011;43(10):984–9. doi:10.1038/ng.921.72. Tabassum R, Chauhan G, Dwivedi OP, et al. Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21. Diabetes. 2013;62(3):977–86. doi:10.2337/db12-0406.73. Saxena R, Saleheen D, Been LF, et al. Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India. Diabetes. 2013;62(5):1746–55. doi:10.2337/db12-1077.74. Sim X, Ong RT-H, Suo C, et al. Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. Gibson G, ed. PLoS Genet. 2011;7(4):e1001363. doi:10.1371/journal.pgen.1001363.75. Haseeb A, Iliyas M, Chakrabarti S, et al. Single-nucleotide polymorphisms in peroxisome proliferator-activated receptor gamma and their association with plasma levels of resistin and the metabolic syndrome in a South Indian population. J Biosci. 2009;34(3):405–14. Available at: . Accessed February 15, 2014.76. Anuradha S, Radha V, Mohan V. Association of novel variants in the hepatocyte nuclear factor 4A gene with maturity onset diabetes of the young and early onset type 2 diabetes. Clin Genet. 2011;80(6):541–9. doi:10.1111/j.1399-0004.2010.01577.x.77. Chandak GR, Janipalli CS, Bhaskar S, et al. Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Diabetologia. 2007;50(1):63–7. doi:10.1007/s00125-006-0502-2.78. Chidambaram M, Radha V, Mohan V. Replication of recently described type 2 diabetes gene variants in a South Indian population. Metabolism. 2010;59(12):1760–6. doi:10.1016/j.metabol.2010.04.024.79. Mukhopadhyaya PN, Acharya A, Chavan Y, Purohit SS, Mutha A. Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in an Indian population. Genet Mol Res. 2010;9(4):2060–8. doi:10.4238/vol9-4gmr883.80. Janipalli CS, Kumar MVK, Vinay DG, et al. Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of Type 2 diabetes and related traits in Indians. Diabet Med. 2012;29(1):121–7. doi:10.1111/j.1464-5491.2011.03438.x.81. Rees SD, Hydrie MZI, Shera AS, et al. Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations. Diabetologia. 2011;54(6):1368–74. doi:10.1007/s00125-011-2063-2.82. Uma Jyothi K, Jayaraj M, Subburaj KS, et al. Association of TCF7L2 gene polymorphisms with T2DM in the population of Hyderabad, India. PLoS One. 2013;8(4):e60212. doi:10.1371/journal.pone.0060212.83. Rees SD, Islam M, Hydrie MZI, et al. An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference. Diabet Med. 2011;28(6):673–80. doi:10.1111/j.1464-5491.2011.03257.x.84. Bodhini D, Radha V, Dhar M, Narayani N, Mohan V. The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism. 2007;56(9):1174–8. doi:10.1016/j.metabol.2007.04.012.85. Raza ST, Abbas S, Ahmed F, Fatima J, Zaidi ZH, Mahdi F. Association of MTHFR and PPARγ2 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population. Gene. 2012;511(2):375–9. doi:10.1016/j.gene.2012.09.072.86. Tan JT, Ng DPK, Nurbaya S, et al. Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore. J Clin Endocrinol Metab. 2010;95(1):390–7. doi:10.1210/jc.2009-0688.87. Humphries SE, Gable D, Cooper JA, et al. Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women. J Mol Med (Berl). 2006;84(12):1005–14. Available at: . Accessed February 15, 2014.88. Radha V, Vimaleswaran KS, Babu HNS, et al. Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity. Diabetes Care. 2006;29(5):1046–51. doi:10.2337/diacare.2951046.89. Boodram LG, Miyake K, Hayes MG, Bell GI, Cockburn BN. Association of the KCNJ11 variant E23K with type 2 diabetes in Indo-Trinidadians. West Indian Med J. 2011;60(6):604–7. Available at: . Accessed February 15, 2014.90. Yajnik CS, Janipalli CS, Bhaskar S, et al. FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians. Diabetologia. 2009;52(2):247–52. doi:10.1007/s00125-008-1186-6.91. Gupta V, Khadgawat R, Ng HKT, et al. A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India. Ann Hum Genet. 2010;74(4):361–8. doi:10.1111/j.1469-1809.2010.00580.x.92. Chauhan G, Spurgeon CJ, Tabassum R, et al. Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians. Diabetes. 2010;59(8):2068–74. doi:10.2337/db09-1386.93. Chauhan G, Tabassum R, Mahajan A, et al. Common variants of FTO and the risk of obesity and type 2 diabetes in Indians. J Hum Genet. 2011;56(10):720–6. doi:10.1038/jhg.2011.87.94. Sanghera DK, Ortega L, Han S, et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet. 2008;9(1):59. doi:10.1186/1471-2350-9-59.95. Lehtovirta M, Kaprio J, Forsblom C, Eriksson J, Tuomilehto J, Groop L. Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins. Diabetologia. 2000;43(3):285–93. doi:10.1007/s001250050046.96. Perry JRB, Voight BF, Yengo L, et al. Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases. PLoS Genet. 2012;8(5):e1002741. doi:10.1371/journal.pgen.1002741.97. Qi Q, Li H, Loos RJF, et al. Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Hum Mol Genet. 2009;18(18):3508–15. doi:10.1093/hmg/ddp294.98. Unoki H, Takahashi A, Kawaguchi T, et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet. 2008;40(9):1098–102. doi:10.1038/ng.208.99. Kraft P. Curses--winner’s and otherwise--in genetic epidemiology. Epidemiology. 2008;19(5):649–51; discussion 657–8. doi:10.1097/EDE.0b013e318181b865.100. Tsai F-J, Yang C-F, Chen C-C, et al. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet. 2010;6(2):e1000847. doi:10.1371/journal.pgen.1000847.101. Zeggini E, Scott LJ, Saxena R, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008;40(5):638–45. doi:10.1038/ng.120.102. Voight BF, Scott LJ, Steinthorsdottir V, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010;42(7):579–89. doi:10.1038/ng.609.103. Li H, Gan W, Lu L, et al. A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans. Diabetes. 2013;62(1):291–8. doi:10.2337/db12-0454.104. DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, et al. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet. 2014;46(3):234–44. doi:10.1038/ng.2897.105. Scott LJ, Mohlke KL, Bonnycastle LL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007;316(5829):1341–5. doi:10.1126/science.1142382.106. Di Rienzo A, Hudson RR. An evolutionary framework for common diseases: the ancestral-susceptibility model. Trends Genet. 2005;21(11):596–601. doi:10.1016/j.tig.2005.08.007.107. Pickrell JK, Coop G, Novembre J, et al. Signals of recent positive selection in a worldwide sample of human populations. Genome Res. 2009;19(5):826–37. doi:10.1101/gr.087577.108.108. Chambers JC, Abbott J, Zhang W, et al. The South Asian genome. PLoS One. 2014;9(8):e102645. doi:10.1371/journal.pone.0102645.109. Ayub Q, Moutsianas L, Chen Y, et al. Revisiting the Thrifty Gene Hypothesis via 65 Loci Associated with Susceptibility to Type 2 Diabetes. Am J Hum Genet. 2014;94(2):176–85. doi:10.1016/j.ajhg.2013.12.010.110. Yang I V, Wade CM, Kang HM, et al. Identification of novel genes that mediate innate immunity using inbred mice. Genetics. 2009;183(4):1535–44. doi:10.1534/genetics.109.107540.111. VanLiere JM, Rosenberg NA. Mathematical properties of the r2 measure of linkage disequilibrium. Theor Popul Biol. 2008;74(1):130–7. doi:10.1016/j.tpb.2008.05.006.112. Rees SD, Hydrie MZI, O’Hare JP, et al. Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes. Timpson NJ, ed. PLoS One. 2011;6(9):e24710. doi:10.1371/journal.pone.0024710.113. De Haan HG, Bezemer ID, Doggen CJM, et al. Multiple SNP testing improves risk prediction of first venous thrombosis. Blood. 2012;120(3):656–63. doi:10.1182/blood-2011-12-397752.114. Cooke JN, Ng MCY, Palmer ND, et al. Genetic risk assessment of type 2 diabetes-associated polymorphisms in African Americans. Diabetes Care. 2012;35(2):287–92. doi:10.2337/dc11-0957.115. Chen H, Poon A, Yeung C, et al. A genetic risk score combining ten psoriasis risk loci improves disease prediction. Mailund T, ed. PLoS One. 2011;6(4):e19454. doi:10.1371/journal.pone.0019454.116. Lin X, Song K, Lim N, et al. Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study. Diabetologia. 2009;52(4):600–8. doi:10.1007/s00125-008-1254-y.117. Sohani ZN, Meyre D, de Souza RJ, et al. Assessing the quality of published genetic association studies in meta-analyses: the quality of genetic studies (Q-Genie) tool. BMC Genet. 2015;16(1):50. doi:10.1186/s12863-015-0211-2.118. Li A, Meyre D. Challenges in reproducibility of genetic association studies: lessons learned from the obesity field. Int J Obes (Lond). 2013;37(4):559–67. doi:10.1038/ijo.2012.82.119. Li A, Meyre D. Jumping on the Train of Personalized Medicine: A Primer for Non- Geneticist Clinicians: Part 3. Clinical Applications in the Personalized Medicine Area. Curr Psychiatry Rev. 2014;10(2):118–132. doi:10.2174/1573400510666140630170549.120. Cirulli ET, Goldstein DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010;11(6):415–25. doi:10.1038/nrg2779.121. Wray NR, Purcell SM, Visscher PM. Synthetic associations created by rare variants do not explain most GWAS results. Flint J, ed. PLoS Biol. 2011;9(1):e1000579. doi:10.1371/journal.pbio.1000579.122. Williams AL, Jacobs SBR, Moreno-Macías H, et al. Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature. 2014;506(7486):97–101. doi:10.1038/nature12828.123. Estrada K, Aukrust I, Bj?rkhaug L, et al. Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population. JAMA. 2014;311(22):2305–14. doi:10.1001/jama.2014.6511.124. Moltke I, Grarup N, J?rgensen ME, et al. A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature. 2014;512(7513):190–3. doi:10.1038/nature13425.125. Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411(6837):599–603. doi:10.1038/35079107.126. Bonnefond A, Clément N, Fawcett K, et al. Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat Genet. 2012;44(3):297–301. doi:10.1038/ng.1053.127. Simmons D, Williams R. Dietary practices among Europeans and different South Asian groups in Coventry. Br J Nutr. 2007;78(01):5. doi:10.1079/BJN19970114.128. Babakus WS, Thompson JL. Physical activity among South Asian women: a systematic, mixed-methods review. Int J Behav Nutr Phys Act. 2012;9(1):150. doi:10.1186/1479-5868-9-150.129. Gerich JE. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr Rev. 1998;19(4):491–503. doi:10.1210/edrv.19.4.0338.130. Gastaldelli A. Role of beta-cell dysfunction, ectopic fat accumulation and insulin resistance in the pathogenesis of type 2 diabetes mellitus. Diabetes Res Clin Pract. 2011;93 Suppl 1:S60–5. doi:10.1016/S0168-8227(11)70015-8.131. Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev. 2008;29(3):351–66. doi:10.1210/er.2007-0023.132. Sohani ZN, Deng WQ, Pare G, Meyre D, Gerstein HC, Anand SS. Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations? Diabetologia. 2014. doi:10.1007/s00125-014-3354-1.133. McKeigue PM, Shah B, Marmot MG. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet. 1991;337(8738):382–6. Available at: . Accessed November 10, 2014.134. Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy SM. Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab. 1999;84(7):2329–35. doi:10.1210/jcem.84.7.5817.135. Misra A. Impact of ethnicity on body fat patterning in Asian Indians and blacks: relation with insulin resistance. Nutrition. 2003;19(9):815–6. Available at: . Accessed November 20, 2014.136. Sniderman AD, Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A. Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis. Int J Epidemiol. 2007;36(1):220–5. doi:10.1093/ije/dyl245.137. Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368(9541):1096–105. doi:10.1016/S0140-6736(06)69420-8.138. Janssens ACJW, Moonesinghe R, Yang Q, Steyerberg EW, van Duijn CM, Khoury MJ. The impact of genotype frequencies on the clinical validity of genomic profiling for predicting common chronic diseases. Genet Med. 2007;9(8):528–535. doi:10.1097/GIM.0b013e31812eece0.139. Keating BJ, Tischfield S, Murray SS, et al. Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. PLoS One. 2008;3(10):e3583. doi:10.1371/journal.pone.0003583.140. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38(8):904–9. doi:10.1038/ng1847.141. Wright S. Coefficients of Inbreeding and Relationship. Am Nat. 1922;56(645):330–338. Available at: . Accessed August 4, 2015.142. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75. doi:10.1086/519795.143. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet. 2011;88(1):76–82. doi:10.1016/j.ajhg.2010.11.011.144. Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011;46(3):399–424. doi:10.1080/00273171.2011.568786.145. Le Floch JP, Escuyer P, Baudin E, Baudon D, Perlemuter L. Blood glucose area under the curve. Methodological aspects. Diabetes Care. 1990;13(2):172–175. doi:10.2337/diacare.13.2.172.146. Hanley AJ, Zinman B, Sheridan P, Yusuf S, Gerstein HC. Effect of Rosiglitazone and Ramipril on {beta}-cell function in people with impaired glucose tolerance or impaired fasting glucose: the DREAM trial. Diabetes Care. 2010;33(3):608–13. doi:10.2337/dc09-1579.147. Utzschneider KM, Prigeon RL, Faulenbach M V, et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2009;32(2):335–41. doi:10.2337/dc08-1478.148. De Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J. 2007;28(7):850–6. doi:10.1093/eurheartj/ehm026.149. De Koning L, Gerstein HC, Bosch J, et al. Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes. Diabetologia. 2010;53(7):1322–1330. doi:10.1007/s00125-010-1710-3.150. Czernichow S, Kengne A-P, Huxley RR, et al. Comparison of waist-to-hip ratio and other obesity indices as predictors of cardiovascular disease risk in people with type-2 diabetes: a prospective cohort study from ADVANCE. Eur J Cardiovasc Prev Rehabil. 2011;18(2):312–9. doi:10.1097/HJR.0b013e32833c1aa3.151. Rees SD, Hydrie MZI, O’Hare JP, et al. Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes. PLoS One. 2011;6(9):e24710. doi:10.1371/journal.pone.0024710.152. Takeuchi F, Katsuya T, Chakrewarthy S, et al. Common variants at the GCK, GCKR, G6PC2-ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations. Diabetologia. 2010;53(2):299–308. doi:10.1007/s00125-009-1595-1.153. Islam M, Jafar TH, Wood AR, et al. Multiple genetic variants explain measurable variance in type 2 diabetes-related traits in Pakistanis. Diabetologia. 2012;55(8):2193–204. doi:10.1007/s00125-012-2560-y.154. MAGIC Investigators. MAGIC Cohorts. Available at: . Accessed May 18, 2015.155. Brady EM, Webb DR, Morris DH, et al. Investigating endothelial activation and oxidative stress in relation to glycaemic control in a multiethnic population. Exp Diabetes Res. 2012;2012:386041. doi:10.1155/2012/386041.156. El-Assaad W, Buteau J, Peyot M-L, et al. Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death. Endocrinology. 2003;144(9):4154–63. doi:10.1210/en.2003-0410.157. McKeigue PM, Shah B, Marmot MG. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet. 1991;337(8738):382–386. doi:10.1016/0140-6736(91)91164-P.158. Jacqueminet S, Briaud I, Rouault C, Reach G, Poitout V. Inhibition of insulin gene expression by long-term exposure of pancreatic beta cells to palmitate is dependent on the presence of a stimulatory glucose concentration. Metabolism. 2000;49(4):532–6. Available at: . Accessed March 18, 2015.159. Zhou YP, Grill V. Long term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans. J Clin Endocrinol Metab. 1995;80(5):1584–90. doi:10.1210/jcem.80.5.7745004.160. Abate N, Carulli L, Cabo-Chan A, Chandalia M, Snell PG, Grundy SM. Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance. J Clin Endocrinol Metab. 2003;88(12):5927–34. doi:10.1210/jc.2003-030453.161. Guettier J-M, Georgopoulos A, Tsai MY, et al. Polymorphisms in the fatty acid-binding protein 2 and apolipoprotein C-III genes are associated with the metabolic syndrome and dyslipidemia in a South Indian population. J Clin Endocrinol Metab. 2005;90(3):1705–11. doi:10.1210/jc.2004-1338.162. Majithia AR, Flannick J, Shahinian P, et al. Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes. Proc Natl Acad Sci U S A. 2014;111(36):13127–32. doi:10.1073/pnas.1410428111.163. Keating BJ, Tischfield S, Murray SS, et al. Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. PLoS One. 2008;3(10):e3583. doi:10.1371/journal.pone.0003583.164. Seldin MF, Shigeta R, Villoslada P, et al. European population substructure: clustering of northern and southern populations. PLoS Genet. 2006;2(9):e143. doi:10.1371/journal.pgen.0020143.165. Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4(1):7. doi:10.1186/s13742-015-0047-8.166. American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists/American College of Endocrinology statement on the use of hemoglobin A1c for the diagnosis of diabetes. Endocr Pract. 16(2):155–6. doi:10.4158/EP.16.2.155.167. International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32(7):1327–34. doi:10.2337/dc09-9033.168. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33 Suppl 1:S62–9. doi:10.2337/dc10-S062.169. Sacks DB, Arnold M, Bakris GL, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care. 2011;34(6):e61–99. doi:10.2337/dc11-9998.170. Sacks DB. A1C versus glucose testing: a comparison. Diabetes Care. 2011;34(2):518–23. doi:10.2337/dc10-1546.171. Wisdom K, Fryzek JP, Havstad SL, Anderson RM, Dreiling MC, Tilley BC. Comparison of laboratory test frequency and test results between African-Americans and Caucasians with diabetes: opportunity for improvement. Findings from a large urban health maintenance organization. Diabetes Care. 1997;20(6):971–7. Available at: . Accessed August 4, 2015.172. Davidson M, Schriger D. Effect of age and race/ethnicity on HbA1c levels in people without known diabetes mellitus: implications for the diagnosis of diabetes. Diabetes Res Clin Pr. 2010;87(3):415–421. Available at: . Accessed August 4, 2015.173. Barrera V, Peinado MA. Evaluation of single CpG sites as proxies of CpG island methylation states at the genome scale. Nucleic Acids Res. 2012;40(22):11490–8. doi:10.1093/nar/gks928.174. Sofer T, Schifano ED, Hoppin JA, Hou L, Baccarelli AA. A-clustering: a novel method for the detection of co-regulated methylation regions, and regions associated with exposure. Bioinformatics. 2013;29(22):2884–2891. doi:10.1093/bioinformatics/btt498.175. Bock C. Analysing and interpreting DNA methylation data. Nat Rev Genet. 2012;13(10):705–19. doi:10.1038/nrg3273.176. Illingworth RS, Bird AP. CpG islands--’a rough guide'. FEBS Lett. 2009;583(11):1713–20. doi:10.1016/j.febslet.2009.04.012.177. Straughen JK, Sipahi L, Uddin M, Misra DP, Misra VK. Racial differences in IGF1 methylation and birth weight. Clin Epigenetics. 2015;7(1):47. doi:10.1186/s13148-015-0080-6.178. King K, Murphy S, Hoyo C. Epigenetic regulation of Newborns’ imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status. J Epidemiol Community Health. 2015. doi:10.1136/jech-2014-204781.179. Horikoshi M, Yaghootkar H, Mook-Kanamori DO, et al. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nat Genet. 2013;45(1):76–82. doi:10.1038/ng.2477.180. Freathy RM, Weedon MN, Bennett A, et al. Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals. Am J Hum Genet. 2007;80(6):1150–61. doi:10.1086/518517.181. Freathy RM, Bennett AJ, Ring SM, et al. Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes. 2009;58(6):1428–33. doi:10.2337/db08-1739.182. Engel SM, Joubert BR, Wu MC, et al. Neonatal genome-wide methylation patterns in relation to birth weight in the Norwegian Mother and Child Cohort. Am J Epidemiol. 2014;179(7):834–42. doi:10.1093/aje/kwt433.183. Turan N, Ghalwash MF, Katari S, Coutifaris C, Obradovic Z, Sapienza C. DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease? BMC Med Genomics. 2012;5(1):10. doi:10.1186/1755-8794-5-10.184. Takaro TK, Scott JA, Allen RW, et al. The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: assessment of environmental exposures. J Expo Sci Environ Epidemiol. 2015. doi:10.1038/jes.2015.7.185. Dick KJ, Nelson CP, Tsaprouni L, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet. 2014;383(9933):1990–8. doi:10.1016/S0140-6736(13)62674-4.186. Woods KA, Camacho-Hübner C, Savage MO, Clark AJ. Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med. 1996;335(18):1363–7. doi:10.1056/NEJM199610313351805.187. Ong K, Kratzsch J, Kiess W, Costello M, Scott C, Dunger D. Size at birth and cord blood levels of insulin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and the soluble IGF-II/mannose-6-phosphate receptor in term human infants. The ALSPAC Study Team. Avon Longitudinal Stu. J Clin Endocrinol Metab. 2000;85(11):4266–9. doi:10.1210/jcem.85.11.6998.188. Abuzzahab MJ, Schneider A, Goddard A, et al. IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation. N Engl J Med. 2003;349(23):2211–22. doi:10.1056/NEJMoa010107.189. Chen Y, Lemire M, Choufani S, et al. Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray. Epigenetics. 2013;8(2):203–9. doi:10.4161/epi.23470.190. Bell JT, Pai AA, Pickrell JK, et al. DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol. 2011;12(1):R10. doi:10.1186/gb-2011-12-1-r10.191. Stranger BE, Stahl EA, Raj T. Progress and promise of genome-wide association studies for human complex trait genetics. Genetics. 2011;187(2):367–83. doi:10.1534/genetics.110.120907.192. Bell CG, Finer S, Lindgren CM, et al. Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus. PLoS One. 2010;5(11):e14040. doi:10.1371/journal.pone.0014040.193. Turan N, Ghalwash MF, Katari S, Coutifaris C, Obradovic Z, Sapienza C. DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease? BMC Med Genomics. 2012;5:10. doi:10.1186/1755-8794-5-10.194. Filiberto AC, Maccani MA, Koestler D, et al. Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta. Epigenetics. 2011;6(5):566–72. Available at: . Accessed April 18, 2015.195. Gillberg L, Jacobsen SC, R?nn T, Br?ns C, Vaag A. PPARGC1A DNA methylation in subcutaneous adipose tissue in low birth weight subjects--impact of 5 days of high-fat overfeeding. Metabolism. 2014;63(2):263–71. doi:10.1016/j.metabol.2013.10.003.196. Michels KB, Harris HR, Barault L. Birthweight, maternal weight trajectories and global DNA methylation of LINE-1 repetitive elements. PLoS One. 2011;6(9):e25254. doi:10.1371/journal.pone.0025254.197. Chen KT, Chen CJ, Gregg EW, Engelgau MM, Narayan KM. Prevalence of type 2 diabetes mellitus in Taiwan: ethnic variation and risk factors. Diabetes Res Clin Pract. 2001;51(1):59–66.198. Simpkin AJ, Suderman M, Gaunt TR, et al. Longitudinal analysis of DNA methylation associated with birth weight and gestational age. Hum Mol Genet. 2015:ddv119–. doi:10.1093/hmg/ddv119.199. Gloyn AL, Braun M, Rorsman P. Type 2 diabetes susceptibility gene TCF7L2 and its role in beta-cell function. Diabetes. 2009;58(4):800–2. doi:10.2337/db09-0099.200. Da Silva Xavier G, Loder MK, McDonald A, et al. TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes. 2009;58(4):894–905. doi:10.2337/db08-1187.201. Groenewoud MJ, Dekker JM, Fritsche A, et al. Variants of CDKAL1 and IGF2BP2 affect first-phase insulin secretion during hyperglycaemic clamps. Diabetologia. 2008;51(9):1659–63. doi:10.1007/s00125-008-1083-z.202. Ohara-Imaizumi M, Yoshida M, Aoyagi K, et al. Deletion of CDKAL1 affects mitochondrial ATP generation and first-phase insulin exocytosis. PLoS One. 2010;5(12):e15553. doi:10.1371/journal.pone.0015553.203. Steinthorsdottir V, Thorleifsson G, Reynisdottir I, et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet. 2007;39(6):770–5. doi:10.1038/ng2043.204. Economides DL, Proudler A, Nicolaides KH. Plasma insulin in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol. 1989;160(5 Pt 1):1091–4. Available at: . Accessed April 7, 2014.205. Davey Smith G. Birth characteristics of offspring and parental diabetes: evidence for the fetal insulin hypothesis. J Epidemiol Community Heal. 2004;58(2):126–128. doi:10.1136/jech.58.2.126.206. Thies HW, Nolte I, Wenk H, Mertens F, Bullerdiek J, Markowski DN. Permanent activation of HMGA2 in lipomas mimics its temporal physiological activation linked to the gain of adipose tissue. Obesity (Silver Spring). 2014;22(1):141–50. doi:10.1002/oby.20137.207. Li Z, Gilbert JA, Zhang Y, et al. An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis. Dev Cell. 2012;23(6):1176–88. doi:10.1016/j.devcel.2012.10.019.208. Orr AW, Pedraza CE, Pallero MA, et al. Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly. J Cell Biol. 2003;161(6):1179–89. doi:10.1083/jcb.200302069.209. Lillis AP, Van Duyn LB, Murphy-Ullrich JE, Strickland DK. LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies. Physiol Rev. 2008;88(3):887–918. doi:10.1152/physrev.00033.2007.210. Liu Q, Zhang J, Zerbinatti C, et al. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system. PLoS Biol. 2011;9(1):e1000575. doi:10.1371/journal.pbio.1000575.211. Okada Y, Kamatani Y, Takahashi A, et al. A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. Hum Mol Genet. 2010;19(11):2303–12. doi:10.1093/hmg/ddq091.212. Dupuis J, Langenberg C, Prokopenko I, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010;42(2):105–16. doi:10.1038/ng.520.213. Teh AL, Pan H, Chen L, et al. The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes. Genome Res. 2014;24(7):1064–74. doi:10.1101/gr.171439.113.214. Fatemi M, Pao MM, Jeong S, et al. Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level. Nucleic Acids Res. 2005;33(20):e176. doi:10.1093/nar/gni180.215. Ueki M, Cordell HJ. Improved statistics for genome-wide interaction analysis. PLoS Genet. 2012;8(4):e1002625. doi:10.1371/journal.pgen.1002625.216. Whincup PH, Kaye SJ, Owen CG, et al. Birth weight and risk of type 2 diabetes: a systematic review. JAMA. 2008;300(24):2886–97. doi:10.1001/jama.2008.886.217. Hattersley AT, McCarthy MI. What makes a good genetic association study? Lancet. 2005;366(9493):1315–23. doi:10.1016/S0140-6736(05)67531-9.218. Gordis L. Epidemiology. 5th editio. Elsevier; 2014. Available at: . Accessed May 11, 2015.219. Wax JR, Lucas FL, Lamont M, Pinette MG, Cartin A, Blackstone J. Maternal and newborn outcomes in planned home birth vs planned hospital births: a metaanalysis. Am J Obstet Gynecol. 2010;203(3):243.e1–8. doi:10.1016/j.ajog.2010.05.028.220. Reading R, Raybould S, Jarvis S. Deprivation, low birth weight, and children’s height: a comparison between rural and urban areas. BMJ. 1993;307(6917):1458–1462. doi:10.1136/bmj.307.6917.1458.221. Ray JG, Jiang D, Sgro M, Shah R, Singh G, Mamdani MM. Thresholds for small for gestational age among newborns of East Asian and South Asian ancestry. J Obstet Gynaecol Can. 2009;31(4):322–30. Available at: . Accessed May 5, 2015.222. Aschard H, Vilhjálmsson BJ, Joshi AD, Price AL, Kraft P. Adjusting for heritable covariates can bias effect estimates in genome-wide association studies. Am J Hum Genet. 2015;96(2):329–39. doi:10.1016/j.ajhg.2014.12.021.223. Mefford J, Witte JS. The Covariate’s Dilemma. PLoS Genet. 2012;8(11):e1003096. doi:10.1371/journal.pgen.1003096.224. Meyre D. Is FTO a type 2 diabetes susceptibility gene? Diabetologia. 2012;55(4):873–6. doi:10.1007/s00125-012-2478-4.225. Zeggini E, Morris A, eds. Analysis of Complex Disease Association Studies: A Practical Guide. Academic Press; 2010. Available at: . Accessed May 5, 2015.226. Cardon LR, Palmer LJ. Population stratification and spurious allelic association. Lancet. 2003;361(9357):598–604. doi:10.1016/S0140-6736(03)12520-2.227. Barfield RT, Almli LM, Kilaru V, et al. Accounting for population stratification in DNA methylation studies. Genet Epidemiol. 2014;38(3):231–41. doi:10.1002/gepi.21789.228. Adkins RM, Krushkal J, Tylavsky FA, Thomas F. Racial differences in gene-specific DNA methylation levels are present at birth. Birth Defects Res A Clin Mol Teratol. 2011;91(8):728–36. doi:10.1002/bdra.20770.229. Heyn H, Moran S, Hernando-Herraez I, et al. DNA methylation contributes to natural human variation. Genome Res. 2013;23(9):1363–72. doi:10.1101/gr.154187.112.230. Pembrey ME, Bygren LO, Kaati G, et al. Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet. 2006;14(2):159–66. doi:10.1038/sj.ejhg.5201538.231. Kerkel K, Spadola A, Yuan E, et al. Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation. Nat Genet. 2008;40(7):904–8. doi:10.1038/ng.174.232. Schalkwyk LC, Meaburn EL, Smith R, et al. Allelic skewing of DNA methylation is widespread across the genome. Am J Hum Genet. 2010;86(2):196–212. doi:10.1016/j.ajhg.2010.01.014.233. Bittles AH. Population stratification and genetic association studies in South Asia. J Mol Genet Med. 2005;1(2):43–8. Available at: . Accessed July 29, 2015.234. Slatkin M. Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. Nat Rev Genet. 2008;9(6):477–85. doi:10.1038/nrg2361.235. Wall JD, Pritchard JK. Haplotype blocks and linkage disequilibrium in the human genome. Nat Rev Genet. 2003;4(8):587–97. doi:10.1038/nrg1123.236. Ma X, Wright J, Dou S, et al. Ethnic divergence and linkage disequilibrium of novel SNPs in the human NLI-IF gene: evidence of human origin and lack of association with tuberculosis susceptibility. J Hum Genet. 2002;47(3):140–5. doi:10.1007/s100380200016.237. Tai ES, Corella D, Deurenberg-Yap M, et al. Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population. J Lipid Res. 2004;45(4):674–85. doi:10.1194/jlr.M300363-JLR200.238. Sanghera DK, Nath SK, Ortega L, et al. TCF7L2 polymorphisms are associated with type 2 diabetes in Khatri Sikhs from North India: genetic variation affects lipid levels. Ann Hum Genet. 2008;72(Pt 4):499–509. doi:10.1111/j.1469-1809.2008.00443.x.239. Rees SD, Bellary S, Britten AC, et al. Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population. BMC Med Genet. 2008;9(1):8. doi:10.1186/1471-2350-9-8.240. Sanghera DK, Been L, Ortega L, et al. Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs. J Hum Genet. 2009;54(3):162–8. doi:10.1038/jhg.2009.7.241. Sanghera DK, Demirci FY, Been L, et al. PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor. Metabolism. 2010;59(4):492–501. doi:10.1016/j.metabol.2009.07.043.242. Vimaleswaran KS, Radha V, Jayapriya MG, et al. Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population. Metabolism. 2010;59(4):457–62. doi:10.1016/j.metabol.2009.07.034.243. Chavali S, Mahajan A, Tabassum R, et al. Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians. J Hum Genet. 2011;56(10):695–700. doi:10.1038/jhg.2011.83.244. Been LF, Ralhan S, Wander GS, et al. Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US. BMC Med Genet. 2011;12(1):18. doi:10.1186/1471-2350-12-18.245. Ramya K, Radha V, Ghosh S, Majumder PP, Mohan V. Genetic variations in the FTO gene are associated with type 2 diabetes and obesity in south Indians (CURES-79). Diabetes Technol Ther. 2011;13(1):33–42. doi:10.1089/dia.2010.0071.246. Been LF, Hatfield JL, Shankar A, et al. A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity. Nutr Metab Cardiovasc Dis. 2012;22(11):944–51. doi:10.1016/j.numecd.2011.01.006.247. Ali S, Chopra R, Manvati S, et al. Replication of type 2 diabetes candidate genes variations in three geographically unrelated Indian population groups. Dewan A, ed. PLoS One. 2013;8(3):e58881. doi:10.1371/journal.pone.0058881.248. Tariq K, Malik SB, Ali SHB, et al. Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy. Mol Vis. 2013;19:710–7. Available at: . Accessed February 16, 2014. AppendicesSupplementary Table 2. SEQ Supplementary_Table_2. \* ARABIC 1 Full search strategy for systematic review1. diabetes.mp. or exp Diabetes Mellitus, Type 2/2. exp Phenotype/ or exp Genetic Variation/ or exp Genetic Predisposition to Disease/ or exp Genotype/ or genetic variants.mp. or exp Polymorphism, Single Nucleotide/3. exp Asian Continental Ancestry Group/ or south asian.mp.4. ASIA$.mp.5. INDIA$.mp. or India/6. BANGLADESH$.mp. or Bangladesh/7. PAKISTAN$.mp. or Pakistan/8. SRI LANKA$.mp. or Sri Lanka/9. CEYLON$.mp. or Sri Lanka/10. exp India/ or india*.mp.11. bengali*.mp.12. indo*.mp.13. gujarat*.mp.14. sikh*.mp.15. sind*.mp.16. genome wide association study.mp. or Genetic Markers/ or exp Genome-Wide Association Study/ or Disease Susceptibility/ or Pedigree/ or Genetic Linkage/ or Genome, Human/17. candidate gene*.mp.18. exp Mutation/ or mutation.mp.19. (south adj2 asia*).mp. [mp=title, abstract, original title, name of substance word, subject heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier]20. niddm.mp.21. type 2 diabetes.mp.22. genetic predisposition.mp. or exp Genetic Predisposition to Disease/23. polymorphism.mp.24. genotype.mp.25. allelic frequenc*.mp.26. genetic linkage.mp.27. genetic marker*.mp.28. phenotype.mp.29. genetic varia*.mp.30. single nucleotide polymorphism.mp.31. punjab*.mp.32. tamil.mp.33. goa.mp.34. kerala.mp.35. sikkim.mp.36. haryana.mp.37. 2 or 16 or 17 or 18 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 3038. rajasthan*.mp.39. bihar*.mp.40. kashmir*.mp.41. maharashtra*.mp.42. pradesh*.mp.43. bharat*.mp.44. 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 19 or 31 or 32 or 33 or 34 or 35 or 36 or 38 or 39 or 40 or 41 or 42 or 4345. type 2 diabet*.mp.46. 1 or 20 or 21 or 4547. 37 and 44 and 4648. limit 47 to animals49. 47 not 48Supplementary Table 2. SEQ Supplementary_Table_2. \* ARABIC 2 Reported SNPs and their proxies in LD (r2 > 0.8) determined using SNAPGeneReported SNPLead SNPr2CDKAL1rs6931514rs77569920.917rs10946398rs77548401rs9295474rs77548400.885FTOrs1421085rs99396090.901rs7193144rs99396090.967rs8050136rs99396091rs9930506rs99396090.839rs3751812rs99396091HHEXrs1111875rs50154800.966HNF4Ars1884613rs48128290.848rs2144908rs48128291rs1884614rs48128291KCNJ11rs5215rs52190.935KCQN1rs2283228rs23378920.867SLC30A8rs11558471rs132666340.960TCF7L2rs4506565rs79031460.892rs7901695rs79031460.892IGF2BP2rs1470579rs44029601CHCHD9rs4295736rs132921361WFS1rs1801214rs100101311Supplementary Table 2. SEQ Supplementary_Table_2. \* ARABIC 3 Characteristics of studies included in the systematic reviewReferenceRegion of originN casesN controlsMean age casesMean age controlsMean fasting glucose cases (mmol/l)Mean fasting glucose controls (mmol/l)Mean BMI casesMean BMI controlsMean WC casesMean WC controlsMean HC casesMean HC controlsWHR casesWHR controls% males cases% males controlsTai J Lipid Res 2004 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1194/jlr.M300363-JLR200", "ISSN" : "0022-2275", "PMID" : "14729856", "abstract" : "We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated receptor gamma (PPARgamma) locus with plasma lipids and insulin resistance-related variables, according to diabetes status, in a large and representative Asian population from Singapore consisting of 2,730 Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk and examined gene-nutrient interactions between these variants and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin. We found differential effects of these gene variants. The Pro12Ala polymorphism was more associated with plasma lipids and fasting glucose concentrations, whereas the C1431T polymorphism was related to the risk of diabetes. Carriers of the 12Ala allele had higher HDL-cholesterol than did Pro12Pro homozygotes (P < 0.05), and the effect of the 12Ala allele on fasting glucose was modified by diabetes status (P < 0.001). After controlling for confounders, carriers of the T allele had decreased risk of diabetes compared with CC homozygotes [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.93; P = 0.011]; this effect was stronger in Indians (OR 0.38, 95% CI 0.15-0.92; P = 0.032). For both polymorphisms, normal subjects carrying the less prevalent allele had higher BMI (P < 0.05). The PUFA/SFA did not modify the effect of these polymorphisms on BMI or insulin.", "author" : [ { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corella", "given" : "Dolores", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deurenberg-Yap", "given" : "Mabel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adiconis", "given" : "Xian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chew", "given" : "Suok Kai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "Chee Eng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ordovas", "given" : "Jose M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of lipid research", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2004", "4" ] ] }, "page" : "674-85", "title" : "Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "237", "plainTextFormattedCitation" : "237", "previouslyFormattedCitation" : "237" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }237Singaporean Indians108305--------------Radha Diabetes Care 2006 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/diacare.2951046", "ISSN" : "0149-5992", "PMID" : "16644635", "abstract" : "OBJECTIVE: To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians.\n\nRESEARCH DESIGN AND METHODS: South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects.\n\nRESULTS: The Caucasian diabetic subjects had significantly lower prevalence of PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas.\n\nCONCLUSIONS: Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.", "author" : [ { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vimaleswaran", "given" : "Karani S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babu", "given" : "Hunsur Narayan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abate", "given" : "Nicola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandalia", "given" : "Manisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Satija", "given" : "Pankaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Majumder", "given" : "Partha P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deepa", "given" : "Raj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Sathyanarayana M R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "1046-51", "title" : "Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "88", "plainTextFormattedCitation" : "88", "previouslyFormattedCitation" : "88" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }88Not specified (US cohort)8161656 (10)42 (13)8.93 (3.6)5.33 (1.3)25.6 (3.7)24.9 (3.7)--------South India79982052 (11)41 (13)8.99 (3.8)4.72 (0.4)25.1 (4.2)23.4 (4.7)--------Humphries J Mol Med 2006 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0946-2716", "PMID" : "17665514", "abstract" : "Common variants of TCF7L2, encoding a beta-cell-expressed transcription factor, are strongly associated with increased risk of type 2 diabetes (T2D). We examined this association using both prospective and case-control designs. A total of 2,676 healthy European white middle-aged men from the prospective NPHSII (158 developed T2D over 15 years surveillance) were genotyped for two intronic SNPs [rs 7903146 (IVS3C>T) and rs12255372 (IVS4G>T)] which showed strong linkage disequilibrium (D' = 0.88, p<0.001; R(2)=0.76, p<0.001). The IVS5T allele frequency was 0.28 (95% CI 0.27-0.29) and 0.33 (0.28-0.39) in healthy and T2D, respectively (p=0.04). Compared to CC men, CT and TT men had an adjusted [for age, body mass index, systolic blood pressure, triglyceride and C-reactive protein levels] hazard ratio for T2D of 1.65 (1.13-2.41) and 1.87 (0.99-3.53), respectively, p<0.01. The population attributable fraction for diabetes risk was 17%. In 1459, European white T2D men and women (60% male), T allele frequency was 0.36 (0.34-0.38), and compared to NPHSII healthy men the OR for T2D for the CT and TT subjects was 1.43 (1.24-1.65) and 2.11 (1.69-2.63), respectively p=<0.0001. A similar effect was observed in 919 T2D Indian Asians [OR=1.50 (1.14-1.99) and 1.64 (1.03-2.63) p=0.003] and 385 Afro-Caribbean subjects [OR=1.25 (0.90-1.75) and 1.32 (0.74-2.33) p=0.17] compared to non-diabetic ethnically matched subjects from South London. Weaker associations were found for the IVS4G>T in all studies. Linkage disequilibrium between the two SNPs was high in Indian Asians (D'=0.94), but much weaker in Afro-Caribbeans (D'=0.17) and haplotype frequencies differed markedly in this group. These results extend previous observations to other ethnic groups, and strongly confirm that TCF7L2 genotype is a major risk factor for development of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gable", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Jackie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ireland", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stephens", "given" : "Jeffrey W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hurel", "given" : "Steven J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Ka Wah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmen", "given" : "Jutta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappuccio", "given" : "Francesco P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elkeles", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godsland", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "George J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talmud", "given" : "Philippa J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of molecular medicine (Berlin, Germany)", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2006", "12" ] ] }, "page" : "1005-14", "title" : "Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women.", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "87", "plainTextFormattedCitation" : "87", "previouslyFormattedCitation" : "87" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }87Not specified841302--------------Chandak Diabetologia 2007 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-006-0502-2", "ISSN" : "0012-186X", "PMID" : "17093941", "abstract" : "AIMS AND HYPOTHESIS: India has the greatest number of diabetic subjects in any one country, but the genetic basis of type 2 diabetes mellitus in India is poorly understood. Common non-coding variants in the transcription factor 7-like 2 gene (TCF7L2) have recently been strongly associated with increased risk of type 2 diabetes in European populations. We investigated whether TCF7L2 variants are also associated with type 2 diabetes mellitus in the Indian population.\n\nMATERIALS AND METHODS: We genotyped type 2 diabetes patients (n = 955) and ethnically matched control subjects (n = 399) by sequencing three single nucleotide polymorphisms (SNPs) (rs7903146, rs12255372 and rs4506565) in TCF7L2.\n\nRESULTS: We observed a strong association with all the polymorphisms, including rs12255372 (odds ratio [OR] 1.50 [95% CI = 1.24-1.82], p = 4.0 x 10(-5)), rs4506565 (OR 1.48 [95% CI = 1.24-1.77], p = 2.0 x 10(-5)) and rs7903146 (OR 1.46 [95% CI = 1.22-1.75], p = 3.0 x 10(-5)). All three variants showed increased relative risk when homozygous rather than heterozygous, with the strongest risk for rs12255372 (OR 2.28 [95% CI = 1.40-3.72] vs OR 1.43 [95% CI = 1.11-1.83]). We found no association of the TCF7L2 genotypes with age at diagnosis, BMI or WHR, but the risk genotype at rs12255372 was associated with higher fasting plasma glucose (p = 0.001), higher 2-h plasma glucose (p = 0.0002) and higher homeostasis model assessment of insulin resistance (HOMA-R; p = 0.012) in non-diabetic subjects.\n\nCONCLUSIONS: Our study in Indian subjects replicates the strong association of TCF7L2 variants with type 2 diabetes in other populations. It also provides evidence that variations in TCF7L2 may play a crucial role in the pathogenesis of type 2 diabetes by influencing both insulin secretion and insulin resistance. TCF7L2 is an important gene for determining susceptibility to type 2 diabetes mellitus and it transgresses the boundaries of ethnicity.", "author" : [ { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohankrishna", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "A T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "1" ] ] }, "page" : "63-7", "title" : "Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "77", "plainTextFormattedCitation" : "77", "previouslyFormattedCitation" : "77" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }77North India95539947.2 (9.3)30.9 (5.1)-5.1 (4.7–5.5)*Men: 25.4 (3.6) Women: 27.1 (3.9)Men: 20.5 (3.1)Women: 19.1 (2.5)----Men: 0.98 (0.06), women: 0.89 (0.06)Men: 0.90 (0.06), women: 0.76 (0.05)53.746.6Bodhini Clin Exp Met 2007 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2007.04.012", "ISSN" : "0026-0495", "PMID" : "17697858", "abstract" : "One thousand thirty-eight normal glucose-tolerant and 1031 type 2 diabetic subjects selected from the Chennai Urban Rural Epidemiology Study were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay to investigate the association of rs12255372(G/T) and rs7903146(C/T) polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene with type 2 diabetes mellitus in Asian Indians. The frequency of the \"T\" allele of both rs12255372(G/T) and rs7903146(C/T) polymorphisms was significantly higher in diabetic subjects (23% and 33%) compared to that in normal glucose-tolerant subjects (19% and 28%; P = .001 and P = .0001, respectively). Logistic regression analysis of the rs12255372(G/T) polymorphism showed that the odds ratio (adjusted for age, sex, and body mass index) was 1.56 (95% confidence interval [CI], 1.03-2.37; P = .034) for the TT genotype and 1.29 (95% CI, 1.06-1.58; P = .011) for the TG genotype when compared with the GG genotype. Adjusted odds ratios for the TT and TC genotypes of the rs7903146(C/T) polymorphism were found to be 1.50 (95% CI, 1.08-2.08; P = .013) and 1.44 (95% CI, 1.18-1.76; P = .0003), respectively, compared with the CC genotype. Normal glucose-tolerant subjects with the TT genotype of rs12255372(G/T) had significantly higher 2-hour plasma glucose levels (mean +/- SD, 6.1 +/- 1.4 mmol/L) than those with the GG genotype (5.6 +/- 1.0 mmol/L, P = .011). Normal glucose-tolerant subjects with the TT genotype of rs7903146(C/T) polymorphism had significantly higher 2-hour plasma glucose levels (mean +/- SD, 6.0 +/- 1.3 mmol/L) than those with the CC genotype (5.6 +/- 1.0 mmol/L, P = .004). In conclusion, the T allele of the rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene confer susceptibility to type 2 diabetes mellitus in Asian Indians.", "author" : [ { "dropping-particle" : "", "family" : "Bodhini", "given" : "Dhanasekaran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhar", "given" : "Monalisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narayani", "given" : "Nagarajan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "1174-8", "title" : "The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "84", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "84" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84South India1031103849 (10)41 (11)9.2 (4.0)4.6 (0.4)25.1 (4.3)23.6 (4.6)90.4 (10.0)83.7 (11.6)------Sanghera BMC Med Genet 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2350-9-59", "ISSN" : "1471-2350", "PMID" : "18598350", "abstract" : "BACKGROUND: Recent genome-wide association (GWA) studies have identified several unsuspected genes associated with type 2 diabetes (T2D) with previously unknown functions. In this investigation, we have examined the role of 9 most significant SNPs reported in GWA studies: [peroxisome proliferator-activated receptor gamma 2 (PPARG2; rs 1801282); insulin-like growth factor two binding protein 2 (IGF2BP2; rs 4402960); cyclin-dependent kinase 5, a regulatory subunit-associated protein1-like 1 (CDK5; rs7754840); a zinc transporter and member of solute carrier family 30 (SLC30A8; rs13266634); a variant found near cyclin-dependent kinase inhibitor 2A (CDKN2A; rs10811661); hematopoietically expressed homeobox (HHEX; rs 1111875); transcription factor-7-like 2 (TCF7L2; rs 10885409); potassium inwardly rectifying channel subfamily J member 11(KCNJ11; rs 5219); and fat mass obesity-associated gene (FTO; rs 9939609)].\n\nMETHODS: We genotyped these SNPs in a case-control sample of 918 individuals consisting of 532 T2D cases and 386 normal glucose tolerant (NGT) subjects of an Asian Sikh community from North India. We tested the association between T2D and each SNP using unconditional logistic regression before and after adjusting for age, gender, and other covariates. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels using multiple linear regression analysis.\n\nRESULTS: Four of the nine SNPs revealed a significant association with T2D; PPARG2 (Pro12Ala) [odds ratio (OR) 0.12; 95% confidence interval (CI) (0.03-0.52); p = 0.005], IGF2BP2 [OR 1.37; 95% CI (1.04-1.82); p = 0.027], TCF7L2 [OR 1.64; 95% CI (1.20-2.24); p = 0.001] and FTO [OR 1.46; 95% CI (1.11-1.93); p = 0.007] after adjusting for age, sex and BMI. Multiple linear regression analysis revealed significant association of two of nine investigated loci with diabetes-related quantitative traits. The 'C' (risk) allele of CDK5 (rs 7754840) was significantly associated with decreased HDL-cholesterol levels in both NGT (p = 0.005) and combined (NGT and T2D) (0.005) groups. The less common 'C' (risk) allele of TCF7L2 (rs 10885409) was associated with increased LDL-cholesterol (p = 0.010) in NGT and total and LDL-cholesterol levels (p = 0.008; p = 0.003, respectively) in combined cohort.\n\nCONCLUSION: To our knowledge, this is first study reporting the role of some recently emerged loci with T2D in a high risk population of As\u2026", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Shizhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jairup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrell", "given" : "Robert E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nath", "given" : "Swapan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "Mohammed I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "59", "title" : "Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "94", "plainTextFormattedCitation" : "94", "previouslyFormattedCitation" : "94" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94North India532386Men: 53.2 (11.1), Women: 55.2 (11.0)Men: 51.7 (15.6), Women: 50.8 (13.0)Men: 10.1 (3.7) Women: 10.0 (3.5)Men: 5.4 (0.6) Women: 5.4 (0.5)Men: 26.6 (4.3); Women: 29.0 (5.5)Men: 26.6 (4.4), Women: 27.5 (4.9)----Men: 0.99 (0.06), Women: 0.93 (0.07)Men: 0.97 (0.07), Women: 0.91 (0.07)56.247.7Sanghera Ann Hum Genet 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-1809.2008.00443.x", "ISSN" : "0003-4800", "PMID" : "18397358", "abstract" : "Recently, the transcription factor-7-like 2 (TCF7L2) gene has been identified as the most important type 2 diabetes mellitus (T2DM) susceptibility gene. Common intronic polymorphisms in this gene have been found to be strongly associated with T2DM susceptibility showing marked reproducibility in multiple populations. The purpose of this study was to confirm the reported association of six TCF7L2 variants in a Khatri Sikh diabetic sample from North India. We genotyped six-associated SNPs in a case-control sample consisting of 556 T2DM cases and 537 controls. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels. We report replication of association of four of the six SNPs with T2DM in this Khatri Sikh sample [rs7903146, (p = 0.010); rs11196205, (p = 0.011); rs10885409, (p = 0.002) and rs4918789, (p = 0.029)], under a dominant model conferring odds ratios (ORs) of 1.39, 1.44, 1.57 and 1.36, respectively. Haplotype analysis provided further evidence of association by showing a significant difference between cases and controls as revealed by the global omnibus test (chi(2)= 19.36; p = 0.0036). Multiple linear regression analysis also revealed the risk allele carriers of three of four significant SNPs (rs7903146, rs11196205, rs10885409) to be significantly associated with increased fasting total cholesterol (p value = 0.019, 0.025, 0.006) and LDL cholesterol levels (p value = 0.021, 0.018, 0.005), respectively. Our findings confirm that the TCF7L2 gene is a major risk factor for development of T2DM in Khatri Sikhs. It also provides new information about the significant impact of TCF7L2 gene variants on plasma cholesterol levels that appear to be independent of BMI.", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nath", "given" : "S K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gambarelli", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim-Howard", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "S K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "G S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "N K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "J J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "M I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of human genetics", "id" : "ITEM-1", "issue" : "Pt 4", "issued" : { "date-parts" : [ [ "2008", "7" ] ] }, "page" : "499-509", "title" : "TCF7L2 polymorphisms are associated with type 2 diabetes in Khatri Sikhs from North India: genetic variation affects lipid levels.", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "238", "plainTextFormattedCitation" : "238", "previouslyFormattedCitation" : "238" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }238North India556537Men: 56.22 (10.9), Women: 55.05 (11.0)Men: 52.58 (15.7), Women: 51.63 (13.0)Men: 9.89 (3.62), Women: 10.0 (3.45)Men: 5.36 (0.56), Women: 5.40 (0.57)Men: 26.42 (4.3), Women: 29.10 (5.5)Men: 26.65 (4.4), Women: 27.40 (4.9)----Men: 0.99 (0.06), Women: 0.93 (0.07)Men: 0.97 (0.07), Women: 0.90 (0.07)55.648.4Rees BMC Med Genet 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2350-9-8", "ISSN" : "1471-2350", "PMID" : "18291022", "abstract" : "BACKGROUND: Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry.\n\nMETHODS: We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects.\n\nRESULTS: The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 - 1.56, p = 1.96 x 10(-3)). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p < or= 1.04 x 10(-7)).\n\nCONCLUSION: Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellary", "given" : "Srikanth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Britten", "given" : "Abigail C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "8", "title" : "Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "239", "plainTextFormattedCitation" : "239", "previouslyFormattedCitation" : "239" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }239Pakistan (Punjab)83143756.9 (12.1)55.0 (11.8)--28.3 (4.7)28.1 (4.9)102.4 (10.7)99.8 (13.1)------Sanghera J Human Genet 2009 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/jhg.2009.7", "ISSN" : "1435-232X", "PMID" : "19247373", "abstract" : "A recent meta-analysis on three genome-wide association (GWA) scans identified six loci (NOTCH2, THADA, ADAMTS9, JAZF1, CDC123/CAMKID and TSPAN8/LGRS) highly associated with type II diabetes (T2D) in Caucasians. This investigation seeks to confirm this association with diabetes and related metabolic traits in Khatri Sikh diabetics of North India. We genotyped highly significant variants from each locus in a case-control cohort consisting of 680 T2D cases and 637 normoglycemic (NG) controls. Only CDC123/CAMKID (rs12779790) replicated earlier evidence of association with T2D under a dominant model (odds ratio (OR): 1.27; 95% confidence interval (CI): 1.02-1.57; P=0.031) during initial testing. However, we could not confirm this association using multiple testing corrections. In a multiple linear-regression analysis, the same variant in the CDC123/CAMKID revealed a marked decrease in fasting insulin levels among 'G' (risk) allele carriers independently in NG controls (P=0.030) and in T2D cases (P=0.009), as well as in the combined sample (P=0.003) after adjusting for covariates. Evidence of impaired beta-cell function was also observed among 'G' (risk) allele carriers in T2D cases (P=0.008) and in a combined cohort (P=0.026). Our data could not confirm the role of the remaining variants with risk either for T2D or quantitative phenotypes measuring insulin secretion or insulin resistance. These findings suggest that CDC123/CAMKID could be a major risk factor for the development of T2D in Sikhs by affecting beta-cell function. To our knowledge, this is the first study reporting the role of recently emerging loci in this high-risk population from the South Asian subcontinent.", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aston", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "3" ] ] }, "page" : "162-8", "title" : "Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "240", "plainTextFormattedCitation" : "240", "previouslyFormattedCitation" : "240" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }240North India (Punjab)680637men: 55.8 (11.2) women: 56.9 (10.8)men: 51.1 (15.1), women: 50.2 (13.2)men: 10.3 (3.7), women: 10.6 (3.8)men: 5.4 (0.7), women: 5.4 (0.7)men: 26.5 (4.7), women: 28.0 (5.0)men: 26.3 (4.5), women: 27.0 (5.1)men: 94.8 (10.5), women: 92.8 (11.4)men: 92.3 (11.5), women: 87.6 (10.8)men: 96.0 (8.4), women: 99.5 (10.3)men: 96.2 (8.8), women: 97.0 (10.2)men: 0.99 (0.31), women: 0.93 (0.15)men: 0.96 (0.09), women: 0.90 (0.16)--Yajnik Diabetologia 2009 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-008-1186-6", "ISSN" : "1432-0428", "PMID" : "19005641", "abstract" : "AIMS AND HYPOTHESIS: Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune.\n\nMETHODS: We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India.\n\nRESULTS: We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13-1.40; p = 3 x 10(-5)). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01-0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09-0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06-1.37; p = 4.0 x 10(-3)), and also for waist circumference and other anthropometric variables.\n\nCONCLUSIONS: Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mani", "given" : "K R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kale", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshpande", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Krishnaveni", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veena", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fall", "given" : "C H D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "M I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "A T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "2" ] ] }, "page" : "247-52", "title" : "FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "90", "plainTextFormattedCitation" : "90", "previouslyFormattedCitation" : "90" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }90North India1453136146.6 (9.3)34.5 (6.1)8.50 (6.89-11.28)*5.06 (4.61-5.56)*Men: 25.4 (4.0), Women: 27.2 (4.3)Men: 21.9 (3.6), Women: 20.9 (4.1)Men: 95.4 (10.7), Women: 92.4 (10.3)Men: 83.2 (10.5), Women: 69.9 (10.4)Men: 97.3 (7.4), Women: 103.2 (10.2)Men: 91.6 (7.5), Women: 90.9 (9.3)Men: 0.98 (0.06), Women: 0.89 (0.06)Men: 0.91 (0.06), Women: 0.77 (0.06)56.353.6Haseeb J Biosci 2009 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0973-7138", "PMID" : "19805902", "abstract" : "Studies on the association of the Pro12Ala and C1431T polymorphisms of PPAR? with diabetes and obesity have revealed extensive population-dependent variations. However, association of these polymorphisms with the metabolic syndrome and its individual components has not been well investigated in the Indian population. The Indian population harbours the maximum number of diabetics in the world who are thus more susceptible to metabolic disorders. We screened a South Indian population (N=699) for a possible association of these polymorphisms with the metabolic syndrome (MS) and type 2 diabetes. We also investigated the correlation of these two single-nucleotide polymorphisms (SNPs) with plasma resistin levels. The C1431T SNP was associated with higher levels of plasma resistin (P=0.017). Furthermore, C1431T was associated with resistin in different tertiles. Prevalence of the 'Pro-C' haplotype decreased with increasing tertiles of resistin (84.1% to 75.4%, P=0.037). Plasma resistin levels were not found to be associated with MS and type 2 diabetes. These results point to a likely association of plasma resistin levels with PPAR? polymorphisms in the Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Haseeb", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iliyas", "given" : "Mohammad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Subhabrata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqui", "given" : "Arif A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naik", "given" : "Sudhir R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Sudip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suragani", "given" : "Madhuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehtesham", "given" : "Nasreen Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of biosciences", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "405-14", "title" : "Single-nucleotide polymorphisms in peroxisome proliferator-activated receptor gamma and their association with plasma levels of resistin and the metabolic syndrome in a South Indian population.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "75", "plainTextFormattedCitation" : "75", "previouslyFormattedCitation" : "75" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }75South India35034961.8 (11.25)61.93 (10.40)------------Chauhan Diabetes 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-1386", "ISSN" : "1939-327X", "PMID" : "20424228", "abstract" : "OBJECTIVE: Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control studies.\n\nRESEARCH DESIGN AND METHODS: We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects.\n\nRESULTS: We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 x 10(-3) to 4.6 x 10(-34)). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71-2.09], P = 4.6 x 10(-34)). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of beta-cell function (P = 6.9 x 10(-8) and 3 x 10(-4), respectively), which looked consistent with recessive and under-dominant models, respectively.\n\nCONCLUSIONS: Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.", "author" : [ { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spurgeon", "given" : "Charles J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "Seema", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "Smita R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "M V Kranthi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "Swami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "Chittaranjan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "Giriraj R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2010", "8" ] ] }, "page" : "2068-74", "title" : "Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "92", "plainTextFormattedCitation" : "92", "previouslyFormattedCitation" : "92" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }92North India (Pune)1467167246 (40–52)*33 (29–37)*8.50 (6.90–11.30)*5.11 (4.67–5.56)*Men: 24.90 (22.80–27.70), Women: 26.90 (24.40–29.60)*Men: 21.18 (19.15–23.62), Women: 19.53 (17.60–22.74)*----Men: 0.97 (0.94-1.02), Women: 0.89 (0.85-0.94)*Men: 0.91 (0.86-0.95), Women: 0.76 (0.73-0.80)*56.352.9North India (Delhi)1019100653 (45–62)*50 (44–60)*7.90 (6.40–10.30)*4.90 (4.50–5.30)*Men: 23.80 (22.00–26.00), Women: 26.70 (24.20–29.20)*Men: 23.20 (20.20–25.70), Women: 24.90 (21.10–28.60)*----Men: 1.00 (0.97–1.03), Women: 1.00 (0.97–1.03)*Men: 0.97 (0.92–1.00), Women: 0.86 (0.82–0.92)*58.160.2Gupta Ann Hum Genet 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-1809.2010.00580.x", "ISSN" : "1469-1809", "PMID" : "20597906", "abstract" : "The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18-clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan-based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p-value = 0.00191; p-value = 0.00179, respectively), and odds ratios of 2.1 (dominant-model) and 2.0 (recessive-model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist-Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single-SNP, combined-SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally-learned sedentary lifestyle and fat-enriched dietary habits, WHR rather than body-mass-index emerged as a robust predictor of risk for T2D in this population.", "author" : [ { "dropping-particle" : "", "family" : "Gupta", "given" : "Vipin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khadgawat", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Hon Keung Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Satish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Ajay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Vadlamudi Raghavendra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sachdeva", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of human genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "361-8", "title" : "A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India.", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "91", "plainTextFormattedCitation" : "91", "previouslyFormattedCitation" : "91" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }91North India219184Men: 59.12 (10.34), Women: 55.65 (10.44)Men: 55.52 (10.61), Women: 51.99 (9.37)--Men: 27.18 (5.75), Women: 30.08 (4.91)Men: 27.48 (7.00), Women: 29.64 (5.27)----Men: 1.01 (0.09), Women: 0.92 (0.08)Men: 1.00 (0.08), Women: 0.89 (0.07)66.251.6Chidambaram Metabolism 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2010.04.024", "ISSN" : "1532-8600", "PMID" : "20580033", "abstract" : "Recent genomewide association studies have identified several new gene variants associated with type 2 diabetes mellitus (T2D) mostly in European populations. These need to be replicated in other populations. We studied 926 unrelated T2D and 812 normal glucose-tolerant subjects randomly selected from the Chennai Urban Rural Epidemiology Study in Southern India. A total of 45 single nucleotide polymorphisms (SNPs) from 15 genes and 13 unannotated loci identified from recent genomewide association T2D studies were genotyped. Only 6 of 45 SNPs studied were replicated in this South Indian population. Three SNPs-rs7756992 (P = .007), rs7754840 (P = .015), and rs6931514 (P = .029)-of the CDKAL1, rs7020996 (P = .003) of the CDKN2A/B gene, rs7923837 (P = .038) of the HHEX gene, and rs12056034 (P = .033) of the BAZ1B gene were associated with T2D in our population. Large-scale studies are needed in our population to validate our findings.", "author" : [ { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2010", "12" ] ] }, "page" : "1760-6", "title" : "Replication of recently described type 2 diabetes gene variants in a South Indian population.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "78", "plainTextFormattedCitation" : "78", "previouslyFormattedCitation" : "78" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }78South India92681252 (11)38 (12)8.97 (4.13)4.68 (0.44)25 (4)23 (4)--------Mukhopadhyaya Genet Mol Res 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4238/vol9-4gmr883", "ISSN" : "1676-5680", "PMID" : "20967696", "abstract" : "A population-based study was undertaken to evaluate linkage between single-nucleotide polymorphisms known as risk factors and type 2 diabetes in an Indian population. The study population was comprised of 40 normal glucose-tolerant individuals (21 males and 19 females) and 40 type 2 diabetes patients (21 males and 19 females). The genes and their corresponding single-nucleotide polymorphisms that we screened were VDR (rs 731236 and rs 1544410), IL-6 (rs 1800795), TCF7L2 (rs 7903146) and TNF-\u03b1 (rs 1800629). The risk alleles were more frequent in the subjects with type 2 diabetes, except for the TNF-\u03b1 gene, which was very infrequent in the population; the normal allele occurred at high and similar frequencies in both normal and diabetic individuals.", "author" : [ { "dropping-particle" : "", "family" : "Mukhopadhyaya", "given" : "P N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Acharya", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavan", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purohit", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutha", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics and molecular research : GMR", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "2060-8", "title" : "Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in an Indian population.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "79", "plainTextFormattedCitation" : "79", "previouslyFormattedCitation" : "79" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }79North India4040Men: 46.0 (14.6), Women: 48.6 (9.0)Men: 42.29 (13.41), Women: 45 (8.83)Men: 10.25 (1.88), Women: 10.28 (1.47)Men: 5.12 (0.94); Women: 5.14 (0.73)Men: 31.9 (5.0), Women: 31.9 (4.0)Men: 27.9 (4.9), Women: 28.4 (4.3)----Men: 0.99 (0.06), Women: 1.01 (0.08)Men: 0.97 (0.06), Women: 0.99 (0.08)52.552.5Sanghera Metabolism 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2009.07.043", "ISSN" : "1532-8600", "PMID" : "19846176", "abstract" : "We have examined the association of 14 tagging single nucleotide polymorphisms (tagSNPs) in peroxisome proliferator activated receptor-gamma transcripts 1 and 2 (PPARG1 and 2) and 5 tagSNPs in adiponectin (ADIPOQ) genes for their effect on type 2 diabetes mellitus (T2D) risk in Asian Indian Sikhs. A total of 554 T2D cases and 527 normoglycemic controls were examined for association with T2D and other subphenotypes of T2D. With the exception of a strong association of PPARG2/Pro12Ala with T2D (odds ratio, 0.13; 95% confidence interval, 0.03-0.56; P = .0007), no other tagSNP in the PPARG locus revealed any significant association with T2D in this population. Similarly, none of the tagSNPs in the ADIPOQ gene was associated with T2D susceptibility in single-site analysis. However, haplotype analysis provided strong evidence of association of these loci with T2D. Three-site haplotype analysis in the PPARG locus using the 2 marginally associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala (P/rs1801282) revealed a strong association of 1 \"risk\" (CGC) (P = .003, permutation P = .015) and 1 \"protective\" (CAC) (P = .001, permutation P = .005) haplotype associated with T2D. However, the major effect still appears to be driven by Pro12Ala, as the association of these haplotypes did not remain significant when analyzed conditional upon Pro12Ala (P = .262). In addition, 2-site haplotype analysis in the ADIPOQ locus using only 2 marginally associated SNPs (AD/rs182052 and AD/rs7649121) revealed a significant protective association of the GA haplotype with T2D (P = .009, permutation P = .026). Multiple linear regression analysis also revealed significant association of an ADIPOQ variant (AD/rs12495941) with total body weight (P = .010), waist (P = .024), and hip (P = .021), although these associations were not significant after adjusting for multiple testing. Our new findings strongly suggest that the genetic variation in PPARG and ADIPOQ loci could contribute to the risk for the development of T2D in Indian Sikhs. Identification of causal SNPs in these important biological and positional candidate genes would help determine the true physiologic significance of these loci in T2D and obesity.", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir Kaur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demirci", "given" : "Fatma Yesim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet Singh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder Kumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jairup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aston", "given" : "Christopher Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "Ilyas Mohammad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "492-501", "title" : "PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "241", "plainTextFormattedCitation" : "241", "previouslyFormattedCitation" : "241" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }241North India554527Men: 56.1 (11.1), Women: 55.2 (11.1)Men: 51.8 (15.6), Women: 51.5 (13.3)Men: 9.4 (3.3), Women: 9.6 (3.1)Men: 5.4 (0.6), Women: 5.5 (0.6)Men: 26.6 ± 4.4; Women: 29.0± 5.4Men: 26.7 (4.2), Women: 27.5 (4.8)----Men: 0.99 (0.08), Women: 0.93 (0.07)Men: 0.97 (0.08), Women: 0.91 (0.07)55.849.0Vimaleswaran Met 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2009.07.034", "ISSN" : "1532-8600", "PMID" : "19846173", "abstract" : "Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone receptor of ligand-dependent transcription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and its related traits in a South Indian population. The study subjects (1000 type 2 diabetes mellitus and 1000 normal-glucose-tolerant subjects) were chosen randomly from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The variants were screened by single-stranded conformational variant, direct sequencing, and restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. The -1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio, 2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of 12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The 3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His) haplotype was associated with a reduced risk of type 2 diabetes mellitus (P < .0001). Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Vimaleswaran", "given" : "Karani S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jayapriya", "given" : "Munuguru Gopal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Majumder", "given" : "Partha P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "M R Sathyanarayana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "457-62", "title" : "Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "242", "plainTextFormattedCitation" : "242", "previouslyFormattedCitation" : "242" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }242South India1000100052 (11)46 (12)--26.1 (4.2)24.0 (4.7)92.3 (9.4)87.2 (11.4)------Tan J Clin End 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2009-0688", "ISSN" : "1945-7197", "PMID" : "19892838", "abstract" : "CONTEXT: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized.\n\nOBJECTIVE: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. Design: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians.\n\nRESULTS: In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.\n\nCONCLUSIONS: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.", "author" : [ { "dropping-particle" : "", "family" : "Tan", "given" : "Jonathan T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel P K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nurbaya", "given" : "Siti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Xiu Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leong", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seet", "given" : "Lin Tze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siew", "given" : "Wei Fong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kon", "given" : "Winston", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saw", "given" : "Seang Mei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jeannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chew", "given" : "Suok Kai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "390-7", "title" : "Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore.", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "86", "plainTextFormattedCitation" : "86", "previouslyFormattedCitation" : "86" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86Singaporean Indians246364--------------Rees Diabet Med 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1464-5491.2011.03257.x", "ISSN" : "1464-5491", "PMID" : "21294771", "abstract" : "AIMS: A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians.\n\nMETHODS: We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged \u226540 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies.\n\nRESULTS: In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95%CI 0.24-0.67) kg/m(2) per A-allele (P=3.0 \u00d7 10(-5) ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P=0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95%CI) 1.18 (1.07-1.30); P=0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95%CI 1.14-1.31); P=1.07 \u00d7 10(-8) ] even after adjusting for BMI [1.18 (95%CI 1.10-1.27); P=1.02 \u00d7 10(-5) ] or waist circumference [1.18 (95%CI 1.10-1.27); P=3.97 \u00d7 10(-5) ].\n\nCONCLUSIONS: The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaudhary", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellary", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashmi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "673-80", "title" : "An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference.", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "83", "plainTextFormattedCitation" : "83", "previouslyFormattedCitation" : "83" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }83Pakistan385128153.5 (10.7)51.1 (10.7)10.6 (4.0)5.3 (0.6)26.7 (5.6)25.2 (5.2)93.2 (11.7)88.1 (12.0)----40.046.3North India and Pakistan1568117755.8 (11.9)56.4 (10.7)-5.4 (0.6)27.5 (4.8)25.7 (5.2)99.8 (11.4)93.8 (13.0)----51.650.0Rees PloS One 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0024710", "ISSN" : "1932-6203", "PMID" : "21949744", "abstract" : "BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed \u03b2 values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (\u03b2\u200a=\u200a0.063 [95% CI: 0.013, 0.113] p\u200a=\u200a0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative \u03b2 value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p\u200a=\u200a1.29\u00d710(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p\u200a=\u200a9.1\u00d710(-4)) and 1.16 (95% CI: 1.05, 1.29; p\u200a=\u200a3.49\u00d710(-3)) respectively.\n\nCONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e24710", "publisher" : "Public Library of Science", "title" : "Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "112", "plainTextFormattedCitation" : "112", "previouslyFormattedCitation" : "112" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }112Pakistan85741756.9 (12.0)54.9 (11.7)--28.6 (4.6)28.0 (4.9)------45.352.0Pakistan821116754.6 (11.7)56.3 (10.8)-5.5 (0.6)26.1 (4.7)24.3 (5.0)------52.452.9Chavali J Human Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/jhg.2011.83", "ISSN" : "1435-232X", "PMID" : "21814221", "abstract" : "Variants in genes involved in pancreatic \u03b2-cell development and function are known to cause monogenic forms of type 2 diabetes and are also associated with complex form. In this study, we studied the genetic association of polymorphisms in such important genes with type 2 diabetes in the high-risk Indians. We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. HNF4A promoter P2 polymorphisms rs1884613 and rs2144908, which are in high linkage disequilibrium, showed significant association with type 2 diabetes (odds ratio (OR)=1.37 (95% confidence interval (CI) 1.19-1.57), P=9.4 \u00d7 10(-6) for rs1884613 and OR=1.37 (95%CI 1.20-1.57), P=6.0 \u00d7 10(-6) for rs2144908), as previously shown in other populations. We observed body mass index-dependent association of these variants with type 2 diabetes in normal-weight/lean subjects. Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 \u00d7 10(-4)). Thus, pancreatic \u03b2-cell development and function genes contribute to susceptibility to type 2 diabetes in North Indians.", "author" : [ { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of human genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10", "4" ] ] }, "language" : "en", "page" : "695-700", "publisher" : "Nature Publishing Group", "title" : "Association of variants in genes involved in pancreatic \u03b2-cell development and function with type 2 diabetes in North Indians.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "243", "plainTextFormattedCitation" : "243", "previouslyFormattedCitation" : "243" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }243North India1019100653 (45-62)*50 (44-60)*7.9 (6.4-10.3)*4.9 (4.5-5.3)*Men: 23.80 (22.00-26.00), Women:26.70 (24.20-29.20)*median: men=23.10 (20.10-25.70), women=25.00 (21.10-28.50)----Men: 1.00 (0.97-1.03), Women: 1.00 (0.97-1.03)*Men: 0.97 (0.92-1.00), Women: 0.86 (0.82-0.92)*58.160.2Boodram West Indian Med J 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0043-3144", "PMID" : "22512215", "abstract" : "OBJECTIVE: To examine the effect of genetic variation in KCNJ11 on the risk of Type 2 diabetes mellitus in Trinidadians.\n\nMETHODS: The coding and bordering intron-exon regions of the KCNJ11 gene were sequenced in 168 diabetic and 61 non-diabetic subjects who historically were thought to be of South Asian Indian ancestry as well as 66 diabetic and 59 non-diabetic subjects of African ancestry. Allele and haplotype frequency differences were calculated between cases and controls and linkage equilibrium was assessed across the KCNJ11 region.\n\nRESULTS: We identified novel missense mutations in both subject groups including A94P and R369C in a diabetic Indo-Trinidadian subject, S113G in a non-diabetic Indo-Trinidadian subject, and S118L in a diabetic Afro-Trinidadian subject. It is unknown if these mutations are pathogenic as other family members were not available for study. Additionally, the common variant E23K was associated with Type 2 diabetes in the Indo-Trinidadian group (OR = 1.797 [1.148-2.814], p = 0.0098).\n\nCONCLUSIONS: Rare variants in KCNJ11 are segregating in the Indo- and Afro-Trinidadian populations and further studies are needed to determine their contribution, if any, to the overall prevalence of diabetes in these groups. Common variants such as E23K may increase the risk in the Indo-Trinidadian population.", "author" : [ { "dropping-particle" : "", "family" : "Boodram", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyake", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayes", "given" : "M G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "G I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cockburn", "given" : "B N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The West Indian medical journal", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "604-7", "title" : "Association of the KCNJ11 variant E23K with type 2 diabetes in Indo-Trinidadians.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "89", "plainTextFormattedCitation" : "89", "previouslyFormattedCitation" : "89" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }89Indo-Trinidadian1686145.11 (12.03)51.68 (17.22)--26.05 (4.47)25.08 (5.03)------27.440.5Rees Diabetologia 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-011-2063-2", "ISSN" : "1432-0428", "PMID" : "21350842", "abstract" : "AIMS/HYPOTHESIS: Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODS: Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur.\n\nRESULTS: SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 \u00d7 10(-12)), BMI (p = 2.25 \u00d7 10(-4)) and age at onset of diabetes (p = 0.002).\n\nCONCLUSIONS/INTERPRETATION: We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "1368-74", "title" : "Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "81", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "81" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81Pakistan16781584UKADS: 56.90 (12.30), DGP: 54.62 (11.67)UKADS: 54.92 (11.75), DGP: 56.27 (10.81)-DGP: 4.75 (0.47)UKADS: 28.56 (4.61), DGP: 26.07 (4.72)UKADS: 28.01 (4.86), DGP: 24.30 (5.03)UKADS: 102.31 (10.48), DGP: 96.78 (11.88)UKADS: 99.75 (11.52), DGP: 91.91 (13.13)----UKADS: 54.7%, DGP: 47.6%UKADS: 47.96%, DGP: 47.13%Sim PLoS Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1001363", "ISSN" : "1553-7404", "PMID" : "21490949", "abstract" : "Recent large genome-wide association studies (GWAS) have identified multiple loci which harbor genetic variants associated with type 2 diabetes mellitus (T2D), many of which encode proteins not previously suspected to be involved in the pathogenesis of T2D. Most GWAS for T2D have focused on populations of European descent, and GWAS conducted in other populations with different ancestry offer a unique opportunity to study the genetic architecture of T2D. We performed genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945 controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians (977 cases, 1,169 controls). In addition to the search for novel variants implicated in T2D, these multi-ethnic cohorts serve to assess the transferability and relevance of the previous findings from European descent populations in the three major ethnic populations of Asia, comprising half of the world's population. Of the SNPs associated with T2D in previous GWAS, only variants at CDKAL1 and HHEX/IDE/KIF11 showed the strongest association with T2D in the meta-analysis including all three ethnic groups. However, consistent direction of effect was observed for many of the other SNPs in our study and in those carried out in European populations. Close examination of the associations at both the CDKAL1 and HHEX/IDE/KIF11 loci provided some evidence of locus and allelic heterogeneity in relation to the associations with T2D. We also detected variation in linkage disequilibrium between populations for most of these loci that have been previously identified. These factors, combined with limited statistical power, may contribute to the failure to detect associations across populations of diverse ethnicity. These findings highlight the value of surveying across diverse racial/ethnic groups towards the fine-mapping efforts for the casual variants and also of the search for variants, which may be population-specific.", "author" : [ { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Rick Twee-Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan-Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik-Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E-Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "editor" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Greg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "4" ] ] }, "page" : "e1001363", "publisher" : "Public Library of Science", "title" : "Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "74", "plainTextFormattedCitation" : "74", "previouslyFormattedCitation" : "74" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }74Singaporean Indians977116960.71 (9.85)55.73 (9.72)--27.06 (5.10)25.33 (4.40)------54.448.4Chauhan J Hum Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/jhg.2011.87", "ISSN" : "1435-232X", "PMID" : "21814223", "abstract" : "Common variants of fat mass and obesity-associated gene (FTO, fat mass- and obesity-associated gene) have been shown to be associated with obesity and type 2 diabetes in population of European and non-European ethnicity. However, studies in Indian population have provided inconsistent results. Here, we examined association of eight FTO variants (rs1421085, rs8050136, rs9939609, rs9930506, rs1861867, rs9926180, rs2540769 and rs708277) with obesity and type 2 diabetes in 5364 North Indians (2474 type 2 diabetes patients and 2890 non-diabetic controls) in two stages. None of the variants including previously reported intron 1 variants (rs1421085, rs8050136, rs9939609 and rs9930506) showed body mass index (BMI)-dependent/independent association with type 2 diabetes. However, rs1421085, rs8050136 and rs9939609 were associated with obesity status and measures of obesity (BMI, waist circumference and waist-to-hip ratio) in stage 2 and combined study population. Meta-analysis of the two study population results also revealed that rs1421085, rs8050136 and rs9939609 were significantly associated with BMI both under the random- and fixed-effect models (P (random/fixed)=0.02/0.0001, 0.004/0.0006 and 0.01/0.01, respectively). In conclusion, common variants of FTO were associated with obesity, but not with type 2 diabetes in North Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahendran", "given" : "Yuvaraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nigam", "given" : "Shubhanchi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubey", "given" : "Himanshu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Binuja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of human genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "720-6", "publisher" : "The Japan Society of Human Genetics", "title" : "Common variants of FTO and the risk of obesity and type 2 diabetes in Indians.", "title-short" : "J Hum Genet", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "93", "plainTextFormattedCitation" : "93", "previouslyFormattedCitation" : "93" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }93North India (replication cohort)1401184855 (48–62)*52 (45–62)*8.05 (6.39–10.60)*4.82 (4.41–5.20)*Men: 25.40 (22.94–28.36), Women: 27.34 (24.46–31.00)*Men: 24.69 (22.15–27.35), Women: 26.30 (23.11–29.23)*Women: 86.68 (40.00-98.00), Men: 90.00 (36.00-98.00)*Women: 88.00 (81.00-95.50), Men: 93.00 (86.00-100.00)*--Women: 0.95 (0.89-0.98), Men: 0.98 (0.96-1.03)*Men: 0.97 (0.92-1.00), Women: 0.87 (0.82-0.91)*60.755.0North India1019100653 (45-62)*50 (44-60)*7.90 (6.40–10.30)*4.90 (4.50–5.30)*Men: 23.80 (22.00–26.00), Women: 26.70 (24.20–29.20)*Men: 23.20 (20.20–25.70), Women: 24.90 (21.10–28.60)*Men: 86.36 (86.36–91.44), Women: 91.44 (86.36–96.52)*Men: 88.50 (80.64–95.00), Women: 85.00 (75.60–93.00)*--Men: 1.0 (0.97-1.03), Women: 1.0 (0.97-1.03)*Men: 0.97 (0.92–1.00), Women: 0.86 (0.82–0.92)*58.160.2Anuradha Clin Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1399-0004.2010.01577.x", "ISSN" : "1399-0004", "PMID" : "21062274", "abstract" : "Variants in hepatocyte nuclear factor 4A (HNF4A) cause maturity onset diabetes of the young (MODY 1). The objective of the study was to screen the coding and the promoter regions of HNF4A mutations in 87 unrelated South Indian subjects with clinically diagnosed MODY with severe forms of diabetes referred to a tertiary diabetes centre. In addition, we looked at the association of common polymorphisms in HNF4 A gene in subjects with MODY (n = 199), early onset type 2 diabetes (T2DM) (n = 505), late onset T2DM (n = 287) and normal glucose tolerance (NGT) (n = 247). We identified three novel mutations in the P2 promoter region of HNF4A, namely -1009 G/C, -129 T/C and -79 C/T. Co-segregation with diabetes was noted with the -1009 G/C and -129 T/C in one MODY family. We also studied eight single nucleotide polymorphisms (SNPs) of HNF4A gene. The frequency of the minor allele of the rs2144908 was significantly higher in subjects with MODY (p < 0.01) and that of rs736823 was significantly higher in early onset T2DM (p = 0.001). Minor allele frequency of rs1884614 and rs2071197 was significantly lower in early onset T2DM when compared to NGT subjects (p < 0.01). Minor allele frequency of Val255Met was significantly lower in MODY, early onset T2DM and late onset T2DM compared to NGT subjects (p < 0.01). This is the first report of MODY 1 mutations from India and shows that 3.4% of clinically diagnosed MODY subjects have MODY 1. In addition, we report SNPs of HNF4A that are both susceptible to, and protective against, MODY and early onset T2DM.", "author" : [ { "dropping-particle" : "", "family" : "Anuradha", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical genetics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "541-9", "title" : "Association of novel variants in the hepatocyte nuclear factor 4A gene with maturity onset diabetes of the young and early onset type 2 diabetes.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "76", "plainTextFormattedCitation" : "76", "previouslyFormattedCitation" : "76" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }76South India (Chennai)792 (505 Early onset) (287 Late onset)247Early onset: 34 (4), Late onset: 52 (7)58 (7)Early onset: 9.5 mmol (3.9), Late onset: 8.5 (3.6)4.7 (0.4)Early onset: 25.7 (4.2), Late onset: 24.8 (4.3)22.4 (0.7)--------Kooner Nat Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }711873139856LOLIPOP 610: 59.4 (9.2); LOLIPOP 317: 54.1 (10.1); SINDI: 60.7 (9.9); PROMIS: 55.0 (9.4)LOLIPOP 610: 53.9 (10.7); LOLIPOP 317: 46.8 (10.1); SINDI: 55.7 (9.7); PROMIS: 52.9 (10.5)LOLIPOP 610: 8.6 (3.1); LOLIPOP 317: 5.2 (0.6); SINDI: 8.9 (2.9); PROMIS: 9.71 (4.44)LOLIPOP 610: 5.2 (0.6); LOLIPOP 317: 5.1 (0.6); SINDI: 5.38 (1.06); PROMIS: 6.89 (2.91)LOLIPOP 610: 28.1 (4.6); LOLIPOP 317: 27.6 (4.7); SINDI: 27.1 (5.1); PROMIS: 26.0 (4.0)LOLIPOP 610: 26.8 (4.2); LOLIPOP 317: 26.6 (4.2); SINDI: 25.3 (4.4); PROMIS: 25.3 (3.9)LOLIPOP 610: 100.8 (11.5); LOLIPOP 317: 100.0 (12.2); SINDI: - ; PROMIS: 92.0 (12.0)LOLIPOP 610: 96.6 (10.9); LOLIPOP 317: 96.3 (11.4); SINDI: - ; PROMIS: 90.1 (11.7)--LOLIPOP 610: 0.99 (0.07); LOLIPOP 317: 0.99 (0.07); SINDI: - ; PROMIS: 0.95 (0.06)LOLIPOP 610: 0.95 (0.07); LOLIPOP 317: 0.95 (0.07); SINDI: - ; PROMIS: 0.94 (0.07)LOLIPOP 610: 82.9; LOLIPOP 317: 100.0; SINDI: 54.4; PROMIS: 76.5LOLIPOP 610: 84.8; LOLIPOP 317: 100.0; SINDI: 48.4; PROMIS: 83Been BMC Med Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2350-12-18", "ISSN" : "1471-2350", "PMID" : "21261977", "abstract" : "BACKGROUND: Polymorphisms in intron 15 of potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) gene have been associated with type II diabetes (T2D) in Japanese genome-wide association studies (GWAS). More recently a meta-analysis of European GWAS has detected a new independent signal associated with T2D in intron 11 of the KCNQ1 gene. The purpose of this investigation is to examine the role of these variants with T2D in populations of Asian Indian descent from India and the US.\n\nMETHODS: We examined the association between four variants in the KCNQ1 gene with T2D and related quantitative traits in a total of 3,310 Asian Indian participants from two different cohorts comprising 2,431 individuals of the Punjabi case-control cohort from the Sikh Diabetes Study and 879 migrant Asian Indians living in the US.\n\nRESULTS: Our data confirmed the association of a new signal at the KCNQ1 locus (rs231362) with T2D showing an allelic odds ratio (OR) of 1.24 95%CI [1.08-1.43], p = 0.002 in the Punjabi cohort. A moderate association with T2D was also seen for rs2237895 in the Punjabi (OR 1.14; p = 0.036) and combined cohorts (meta-analysis OR 1.14; p = 0.018). Three-site haplotype analysis of rs231362, rs2237892, rs2237895 exhibited considerably stronger evidence of association of the GCC haplotype with T2D showing OR of 1.24 95%CI [1.00-1.53], p = 0.001, permutation p = 8 \u00d7 10-4 in combined cohorts. The 'C' risk allele carriers of rs2237895 had significantly reduced measures of HOMA-B in the US cohort (p = 0.008) as well as in combined cohort in meta-analysis (p = 0.009).\n\nCONCLUSIONS: Our investigation has confirmed that the variation within the KCNQ1 locus confers a significant risk to T2D among Asian Indians. Haplotype analysis further suggested that the T2D risk associated with KCNQ1 SNPs may be derived from 'G' allele of rs231362 and 'C' allele of rs2237895 and this appears to be mediated through \u03b2 cell function.", "author" : [ { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "JaiRup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aston", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "18", "title" : "Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "244", "plainTextFormattedCitation" : "244", "previouslyFormattedCitation" : "244" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }244Not specified (US cohort)139557--8.10 (2.4)5.47 (0.7)----------North India12901019--9.03 (3.5)5.27 (0.74)----------Ramya Diabetes Technol Ther 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1089/dia.2010.0071", "ISSN" : "1557-8593", "PMID" : "21175269", "abstract" : "AIM: the present study investigated the association of six variants-rs9940128, rs7193144, and rs8050136 (in intron 1), rs918031 and rs1588413 (in intron 8), and rs11076023 (3' untranslated region)-across three regulatory regions of the fat mass and obesity-associated (FTO) gene with obesity and type 2 diabetes mellitus (T2DM) in a South Indian population.\n\nMETHODS: unrelated study subjects (n\u2009=\u20091,852; 1,001 normal glucose-tolerant [NGT] controls and 851 cases [T2DM]) were randomly selected from the Chennai Urban Rural Epidemiological Study (CURES). Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism method, and 20% of samples were sequenced to validate the genotypes obtained. Haplotype analysis was also carried out.\n\nRESULTS: the three polymorphisms rs9940128 A/G, rs1588413 C/T, and rs11076023 A/T of the FTO gene were associated with T2DM in our study population. The rs8050136 C/A variant was associated with obesity, and its association with T2DM was also mediated through obesity. The rs1588413 C/T variant showed an association with obesity in the total study subjects, but when the NGT subjects alone were analyzed, the association with obesity was lost. The haplotype ACCTCT confers a lower risk of T2DM in this South Indian population.\n\nCONCLUSIONS: among South Indians, the rs9940128 A/G, rs11076023 A/T, and rs1588413 C/T variants of the FTO gene were associated with T2DM, whereas the rs8050136 C/A variant was associated with obesity.", "author" : [ { "dropping-particle" : "", "family" : "Ramya", "given" : "Kandaswamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Majumder", "given" : "Partha P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes technology & therapeutics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "33-42", "title" : "Genetic variations in the FTO gene are associated with type 2 diabetes and obesity in south Indians (CURES-79).", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "245", "plainTextFormattedCitation" : "245", "previouslyFormattedCitation" : "245" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }245South India851100151 (11)41 (13)9.0 (3.9)4.7 (0.4)25.3 (4.3)23.4 (4.7)91.0 (10.1)83.5 (12.1)98.0 (10.0)94.0 (10.0)--44.341.8Janipali Diabetic Med 2012 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1464-5491.2011.03438.x", "ISSN" : "1464-5491", "PMID" : "21913964", "abstract" : "AIMS: Recent genome-wide association studies have identified several Type 2 diabetes-related loci. We investigated the effect of susceptibility genetic variants, individually, together and in combination with conventional risk factors, on Type 2 diabetes and diabetes-related traits in Indians.\n\nMETHODS: We genotyped 33 variants in 1808 Indian patients and 1549 control subjects and performed association analyses with Type 2 diabetes and related traits using an additive model for individual variant and for genetic risk score based on 32 polymorphisms. The discriminatory value of genetic risk over conventional risk factors was analysed using receiver-operating characteristics curve analysis.\n\nRESULTS: The allelic odds ratio ranged from 1.01 (95% CI 0.85-1.19) to 1.66 (95% CI 1.32-2.01) for single-variant analyses. Although, only 16 variants had significant odds ratios, the direction of association for others was similar to earlier reports. The odds ratio for Type 2 diabetes at each genetic risk score point was 1.11 (95% CI 1.09-1.14; P = 5.6 \u00d7 10(-17)) and individuals with extremes of genetic risk score (\u2265 29.0 and \u2264 17.0) had a 7.5-fold difference in risk of Type 2 diabetes. The discrimination rate between control subjects and patients improved marginally on addition of genetic risk score to conventional risk factors (area under curve = 0.959 and 0.963, respectively; P = 0.001). Of all the quantitative traits analysed, MC4R variants showed strong association with BMI (P = 4.1 \u00d7 10(-4)), fat mass per cent (P = 2.4 \u00d7 10(-4)) and other obesity-related traits, including waist circumference and hip circumference (P = 2.0 \u00d7 10(-3) for both), as well as insulin resistance (P =0.02).\n\nCONCLUSIONS: We replicated the association of well-established common variants with Type 2 diabetes in Indians and observed a similar association as reported in Western populations. Combined analysis of 32 variants aids identification of subgroups at increased risk of Type 2 diabetes, but adds only a minor advantage over conventional risk factors.", "author" : [ { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "M V K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinay", "given" : "D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandeep", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aruna", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Joglekar", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Priyadharshini", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maheshwari", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "121-7", "title" : "Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of Type 2 diabetes and related traits in Indians.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80", "plainTextFormattedCitation" : "80", "previouslyFormattedCitation" : "80" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80North India1808154951.8 (45.6-58.6)40.0 (36.1-44.4)8.2 (6.7-11.0)5.1 (4.8-5.5)25.7 (23.4-28.6)19.4 (17.7-21.7)----0.90 (0.88-0.99)0.84 (0.77-0.91)55.853.2Been Nutr Metab 2012 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.numecd.2011.01.006", "ISSN" : "1590-3729", "PMID" : "21558052", "abstract" : "Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), \u03b2-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low \u2264 25 kg/m(2) and high > 25 kg/m(2)) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (\u03b2 = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (\u03b2 = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation.", "author" : [ { "dropping-particle" : "", "family" : "Been", "given" : "L F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatfield", "given" : "J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shankar", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aston", "given" : "C E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "G S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "N K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "J J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nutrition, metabolism, and cardiovascular diseases : NMCD", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2012", "11" ] ] }, "page" : "944-51", "title" : "A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "246", "plainTextFormattedCitation" : "246", "previouslyFormattedCitation" : "246" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }246North India12011021Men: 54.1 (10.2), Women: 53.7 (9.8)Men: 51.3 (15.2), Women: 50.1 (13.3)Men: 9.09 (3.4), Women: 9.06 (3.6)Men: 5.29 (0.6), Women: 5.20 (0.6)Men: 26.6 (4.4), Women: 28.4 (5.4)Men: 25.7 (4.8), Women: 27.1 (6.7)------52.352.4Raza Gene 2012 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gene.2012.09.072", "ISSN" : "1879-0038", "PMID" : "23036708", "abstract" : "BACKGROUND: Type 2 diabetes mellitus is a multifactorial and polygenic disease, which is considered as a major life threatening problem all over the world. There has been a worldwide effort in the identification of susceptibility genes for type 2 diabetes mellitus and its complications. At present, adequate data is not available dealing with MTHFR (rs1801133) and PPAR\u03b32 (rs1801282) gene polymorphisms and its association with type 2 diabetes mellitus cases among north Indian populations. Thus, we conceived the need for further studies to investigate MTHFR and PPAR\u03b32 gene polymorphisms and their susceptibility to type 2 diabetes mellitus in north Indian population.\n\nMATERIALS AND METHODS: In this study, a total 175 subjects including 87 type 2 diabetes mellitus cases and 88 controls were enrolled. MTHFR and PPAR\u03b32 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).\n\nRESULTS: The MTHFR gene CC, CT, TT genotype frequencies obtained were 40%, 43%, and 17% in type 2 diabetes mellitus cases and 56%, 29%, and 15% in healthy controls respectively. The OR for CC was 0.54 (95%CI 0.29-0.98, P=0.041, \u03c7(2)=4.18, power=0.98), for CT 1.76 (95%CI 0.94-3.30, P=0.07, \u03c7(2)=3.2, power=0.96), and for TT 1.2 (95%CI 0.53-2.70, P=0.66, \u03c7(2)=0.198, power=0.76). The PPAR\u03b32 gene GG CG, CC genotype frequencies obtained were 28%, 41%, and 31% in cases and 40%, 39%, and 21% in healthy controls respectively. OR for GG was 0.58 (95%CI 0.30-1.09, P=0.08, \u03c7(2)=2.9, power=0.96), for CG 1.12 (95%CI 0.61-2.05, P=0.71, \u03c7(2)=0.137, power=0.778), and for CC 1.63 (95%CI 0.82-3.23, P=0.156, \u03c7(2)=2.01, power=0.92).\n\nCONCLUSION: It might be recommended that MTHFR CC genotype seems to be a good marker for the early identification of population at risk of type 2 diabetes mellitus. While we have detected significant difference in allelic frequencies of PPAR\u03b32 C (Proline) and G (Alanine), but at genotypic level significant difference was not detected in this case-control study. Further study with larger groups may be required to validate the study.", "author" : [ { "dropping-particle" : "", "family" : "Raza", "given" : "Syed Tasleem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbas", "given" : "Shania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahmed", "given" : "Faisal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fatima", "given" : "Jalees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaidi", "given" : "Zeashan Haider", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahdi", "given" : "Farzana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gene", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "12", "15" ] ] }, "page" : "375-9", "title" : "Association of MTHFR and PPAR\u03b32 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population.", "type" : "article-journal", "volume" : "511" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "85", "plainTextFormattedCitation" : "85", "previouslyFormattedCitation" : "85" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }85North India878848.47 (12.16)33.79 (12.07)--25.80 (3.97)23.35 (3.02)------67.853.4Anand Diabetes Care 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc12-2553", "ISSN" : "1935-5548", "PMID" : "23603917", "abstract" : "OBJECTIVE: To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.\n\nRESEARCH DESIGN AND METHODS: In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.\n\nRESULTS: Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).\n\nCONCLUSIONS: T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Changchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xiaohe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Jackie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keavney", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudet", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "2836-42", "title" : "Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "62" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62Not specified638212547.72 (9.40)44.14 (9.22)7.35 (2.87)4.80 (0.78)27.0 (4.1)26.3 (4.4)100.9 (10.2)100.1 (10.4)----40.550.8Ali PLoS One 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0058881", "ISSN" : "1932-6203", "PMID" : "23527042", "abstract" : "Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E-04) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value\u200a=\u200a2.05E-08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR\u200a=\u200a2.44, (95%CI\u200a=\u200a1.67-3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.", "author" : [ { "dropping-particle" : "", "family" : "Ali", "given" : "Shafat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chopra", "given" : "Rupali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manvati", "given" : "Siddharth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Yoginder Pal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaul", "given" : "Nabodita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Behura", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Ankit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehajpal", "given" : "Prabodh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Subash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhar", "given" : "Manoj K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chainy", "given" : "Gagan B N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhanwer", "given" : "Amarjit S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Swarkar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bamezai", "given" : "Rameshwar N K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Dewan", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "e58881", "publisher" : "Public Library of Science", "title" : "Replication of type 2 diabetes candidate genes variations in three geographically unrelated Indian population groups.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "247", "plainTextFormattedCitation" : "247", "previouslyFormattedCitation" : "247" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }247North India1583131753.28 (10.13)51.47 (12.40)8.82 (3.36)4.64 (0.66)25.86 (4.76)24.82 (4.35)--------Sexena Diabetes 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1077", "ISSN" : "1939-327X", "PMID" : "23300278", "abstract" : "We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10\u207b\u00b3) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10\u207b\u2074) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 \u00d7 10\u207b\u2078) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10\u207b\u00b3) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10\u207b\u2074) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10\u207b\u2075 to < 10\u207b\u2077), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garavito", "given" : "Martha L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjonnes", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Weang Kee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yasushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirose", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jai Rup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "M Ilyas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maegawa", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobe", "given" : "Kazuyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "page" : "1746-55", "title" : "Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "73", "plainTextFormattedCitation" : "73", "previouslyFormattedCitation" : "73" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }731948227821--------Tabassum Diabetes 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72South India15451304--------North India51934493--------Uma Jyothi PLoS One 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0060212", "ISSN" : "1932-6203", "PMID" : "23577093", "abstract" : "We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established.", "author" : [ { "dropping-particle" : "", "family" : "Uma Jyothi", "given" : "Kommoju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jayaraj", "given" : "Maruda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subburaj", "given" : "Kadarkarai Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Kotla Jaya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumuda", "given" : "Irgam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakshmi", "given" : "Velaga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Battini Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "e60212", "title" : "Association of TCF7L2 gene polymorphisms with T2DM in the population of Hyderabad, India.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "82", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "82" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82South India75862152.5 (9.08)52.2 (7.55)6.41 (1.8)-27.07 (4.63)24.72 (4.62)----1.69 (0.43)0.94 (0.03)58.463.6Tariq Mol Vis 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1090-0535", "PMID" : "23559865", "abstract" : "PURPOSE: The association of non-synonymous substitution polymorphism rs1801282 (c.34C>G, p.Pro12Ala) in exon 4 of the peroxisome proliferator activated receptor gamma gene with diabetic retinopathy (DR) has been reported inconsistently. Therefore, the purpose of the present study was to understand the population-specific role of the Pro12Ala polymorphism in DR susceptibility in Pakistani subjects.\n\nMETHODS: A total of 180 subjects with DR, 193 subjects with type 2 diabetes mellitus (T2DM) with no diabetic retinopathy, and 200 healthy normoglycemic non-retinopathic Pakistani individuals were genotyped for the rs1801282 (c.34C>G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism.\n\nRESULTS: We found the individuals with T2DM carrying 12Ala were at a reduced risk of developing DR (odds ratio [OR]=0.53; 95% confidence interval [CI]=0.33-0.87). Upon stratified analysis regarding disease severity, we observed this protective effect was confined to proliferative DR (OR=0.4; 95% CI=0.2-0.8) with non-significant effects on the susceptibility of non-proliferative DR (OR=0.67; 95% CI=0.37-1.19).\n\nCONCLUSIONS: We report a protective role of the 12Ala polymorphism against proliferative DR in individuals with T2DM in Pakistan.", "author" : [ { "dropping-particle" : "", "family" : "Tariq", "given" : "Khadija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malik", "given" : "Saira Bano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ali", "given" : "Syeda Hafiza Benish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maqsood", "given" : "Sundas Ejaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Azam", "given" : "Aisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muslim", "given" : "Irfan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Muhammad Shakil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Azam", "given" : "Maleeha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waheed", "given" : "Nadia Khalida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qamar", "given" : "Raheel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular vision", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "710-7", "title" : "Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "248", "plainTextFormattedCitation" : "248", "previouslyFormattedCitation" : "248" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }248Pakistan373200----------48.550.0Supplementary Table 2. SEQ Supplementary_Table_2. \* ARABIC 4 Risk of bias assessment for studies included in the systematic reviewReferenceHWE tested in controlsGenotyping call rate > 95%Source of casesSource of controlsTai J Lipid Res 2004 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1194/jlr.M300363-JLR200", "ISSN" : "0022-2275", "PMID" : "14729856", "abstract" : "We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated receptor gamma (PPARgamma) locus with plasma lipids and insulin resistance-related variables, according to diabetes status, in a large and representative Asian population from Singapore consisting of 2,730 Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk and examined gene-nutrient interactions between these variants and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin. We found differential effects of these gene variants. The Pro12Ala polymorphism was more associated with plasma lipids and fasting glucose concentrations, whereas the C1431T polymorphism was related to the risk of diabetes. Carriers of the 12Ala allele had higher HDL-cholesterol than did Pro12Pro homozygotes (P < 0.05), and the effect of the 12Ala allele on fasting glucose was modified by diabetes status (P < 0.001). After controlling for confounders, carriers of the T allele had decreased risk of diabetes compared with CC homozygotes [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.93; P = 0.011]; this effect was stronger in Indians (OR 0.38, 95% CI 0.15-0.92; P = 0.032). For both polymorphisms, normal subjects carrying the less prevalent allele had higher BMI (P < 0.05). The PUFA/SFA did not modify the effect of these polymorphisms on BMI or insulin.", "author" : [ { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corella", "given" : "Dolores", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deurenberg-Yap", "given" : "Mabel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adiconis", "given" : "Xian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chew", "given" : "Suok Kai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tan", "given" : "Chee Eng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ordovas", "given" : "Jose M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of lipid research", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2004", "4" ] ] }, "page" : "674-85", "title" : "Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population.", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "237", "plainTextFormattedCitation" : "237", "previouslyFormattedCitation" : "237" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }237Ynot reported; 20% re-genotyped with 100% concordancegeneral populationgeneral populationRadha Diabetes Care 2006 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/diacare.2951046", "ISSN" : "0149-5992", "PMID" : "16644635", "abstract" : "OBJECTIVE: To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians.\n\nRESEARCH DESIGN AND METHODS: South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects.\n\nRESULTS: The Caucasian diabetic subjects had significantly lower prevalence of PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas.\n\nCONCLUSIONS: Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.", "author" : [ { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vimaleswaran", "given" : "Karani S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Babu", "given" : "Hunsur Narayan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abate", "given" : "Nicola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandalia", "given" : "Manisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Satija", "given" : "Pankaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundy", "given" : "Scott M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Majumder", "given" : "Partha P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deepa", "given" : "Raj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Sathyanarayana M R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "1046-51", "title" : "Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "88", "plainTextFormattedCitation" : "88", "previouslyFormattedCitation" : "88" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }88Ynot reportedgeneral populationgeneral populationHumphries J Mol Med 2006 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0946-2716", "PMID" : "17665514", "abstract" : "Common variants of TCF7L2, encoding a beta-cell-expressed transcription factor, are strongly associated with increased risk of type 2 diabetes (T2D). We examined this association using both prospective and case-control designs. A total of 2,676 healthy European white middle-aged men from the prospective NPHSII (158 developed T2D over 15 years surveillance) were genotyped for two intronic SNPs [rs 7903146 (IVS3C>T) and rs12255372 (IVS4G>T)] which showed strong linkage disequilibrium (D' = 0.88, p<0.001; R(2)=0.76, p<0.001). The IVS5T allele frequency was 0.28 (95% CI 0.27-0.29) and 0.33 (0.28-0.39) in healthy and T2D, respectively (p=0.04). Compared to CC men, CT and TT men had an adjusted [for age, body mass index, systolic blood pressure, triglyceride and C-reactive protein levels] hazard ratio for T2D of 1.65 (1.13-2.41) and 1.87 (0.99-3.53), respectively, p<0.01. The population attributable fraction for diabetes risk was 17%. In 1459, European white T2D men and women (60% male), T allele frequency was 0.36 (0.34-0.38), and compared to NPHSII healthy men the OR for T2D for the CT and TT subjects was 1.43 (1.24-1.65) and 2.11 (1.69-2.63), respectively p=<0.0001. A similar effect was observed in 919 T2D Indian Asians [OR=1.50 (1.14-1.99) and 1.64 (1.03-2.63) p=0.003] and 385 Afro-Caribbean subjects [OR=1.25 (0.90-1.75) and 1.32 (0.74-2.33) p=0.17] compared to non-diabetic ethnically matched subjects from South London. Weaker associations were found for the IVS4G>T in all studies. Linkage disequilibrium between the two SNPs was high in Indian Asians (D'=0.94), but much weaker in Afro-Caribbeans (D'=0.17) and haplotype frequencies differed markedly in this group. These results extend previous observations to other ethnic groups, and strongly confirm that TCF7L2 genotype is a major risk factor for development of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Humphries", "given" : "Steve E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gable", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Jackie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ireland", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stephens", "given" : "Jeffrey W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hurel", "given" : "Steven J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Ka Wah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmen", "given" : "Jutta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Michelle A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappuccio", "given" : "Francesco P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elkeles", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Godsland", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "George J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Talmud", "given" : "Philippa J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of molecular medicine (Berlin, Germany)", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2006", "12" ] ] }, "page" : "1005-14", "title" : "Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women.", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "87", "plainTextFormattedCitation" : "87", "previouslyFormattedCitation" : "87" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }87Ynot reportedWHSS: recruited from general practice clinics, PREDICT: recruited from the diabetes clinics, UCS: recruited from the diabetes clinicsWHSS: recruited from general practice clinicsChandak Diabetologia 2007 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-006-0502-2", "ISSN" : "0012-186X", "PMID" : "17093941", "abstract" : "AIMS AND HYPOTHESIS: India has the greatest number of diabetic subjects in any one country, but the genetic basis of type 2 diabetes mellitus in India is poorly understood. Common non-coding variants in the transcription factor 7-like 2 gene (TCF7L2) have recently been strongly associated with increased risk of type 2 diabetes in European populations. We investigated whether TCF7L2 variants are also associated with type 2 diabetes mellitus in the Indian population.\n\nMATERIALS AND METHODS: We genotyped type 2 diabetes patients (n = 955) and ethnically matched control subjects (n = 399) by sequencing three single nucleotide polymorphisms (SNPs) (rs7903146, rs12255372 and rs4506565) in TCF7L2.\n\nRESULTS: We observed a strong association with all the polymorphisms, including rs12255372 (odds ratio [OR] 1.50 [95% CI = 1.24-1.82], p = 4.0 x 10(-5)), rs4506565 (OR 1.48 [95% CI = 1.24-1.77], p = 2.0 x 10(-5)) and rs7903146 (OR 1.46 [95% CI = 1.22-1.75], p = 3.0 x 10(-5)). All three variants showed increased relative risk when homozygous rather than heterozygous, with the strongest risk for rs12255372 (OR 2.28 [95% CI = 1.40-3.72] vs OR 1.43 [95% CI = 1.11-1.83]). We found no association of the TCF7L2 genotypes with age at diagnosis, BMI or WHR, but the risk genotype at rs12255372 was associated with higher fasting plasma glucose (p = 0.001), higher 2-h plasma glucose (p = 0.0002) and higher homeostasis model assessment of insulin resistance (HOMA-R; p = 0.012) in non-diabetic subjects.\n\nCONCLUSIONS: Our study in Indian subjects replicates the strong association of TCF7L2 variants with type 2 diabetes in other populations. It also provides evidence that variations in TCF7L2 may play a crucial role in the pathogenesis of type 2 diabetes by influencing both insulin secretion and insulin resistance. TCF7L2 is an important gene for determining susceptibility to type 2 diabetes mellitus and it transgresses the boundaries of ethnicity.", "author" : [ { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohankrishna", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "A T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "1" ] ] }, "page" : "63-7", "title" : "Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "77", "plainTextFormattedCitation" : "77", "previouslyFormattedCitation" : "77" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }77Ynot reported; 15% were re-genotyped with 99.9% concordancerecruited from Diabetes Clinic of the King EdwardMemorial Hospital and Research Centre in Puneparents of children in the Pune Maternal Nutrition StudyBodhini Clin Exp Met 2007 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2007.04.012", "ISSN" : "0026-0495", "PMID" : "17697858", "abstract" : "One thousand thirty-eight normal glucose-tolerant and 1031 type 2 diabetic subjects selected from the Chennai Urban Rural Epidemiology Study were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay to investigate the association of rs12255372(G/T) and rs7903146(C/T) polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene with type 2 diabetes mellitus in Asian Indians. The frequency of the \"T\" allele of both rs12255372(G/T) and rs7903146(C/T) polymorphisms was significantly higher in diabetic subjects (23% and 33%) compared to that in normal glucose-tolerant subjects (19% and 28%; P = .001 and P = .0001, respectively). Logistic regression analysis of the rs12255372(G/T) polymorphism showed that the odds ratio (adjusted for age, sex, and body mass index) was 1.56 (95% confidence interval [CI], 1.03-2.37; P = .034) for the TT genotype and 1.29 (95% CI, 1.06-1.58; P = .011) for the TG genotype when compared with the GG genotype. Adjusted odds ratios for the TT and TC genotypes of the rs7903146(C/T) polymorphism were found to be 1.50 (95% CI, 1.08-2.08; P = .013) and 1.44 (95% CI, 1.18-1.76; P = .0003), respectively, compared with the CC genotype. Normal glucose-tolerant subjects with the TT genotype of rs12255372(G/T) had significantly higher 2-hour plasma glucose levels (mean +/- SD, 6.1 +/- 1.4 mmol/L) than those with the GG genotype (5.6 +/- 1.0 mmol/L, P = .011). Normal glucose-tolerant subjects with the TT genotype of rs7903146(C/T) polymorphism had significantly higher 2-hour plasma glucose levels (mean +/- SD, 6.0 +/- 1.3 mmol/L) than those with the CC genotype (5.6 +/- 1.0 mmol/L, P = .004). In conclusion, the T allele of the rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene confer susceptibility to type 2 diabetes mellitus in Asian Indians.", "author" : [ { "dropping-particle" : "", "family" : "Bodhini", "given" : "Dhanasekaran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhar", "given" : "Monalisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narayani", "given" : "Nagarajan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "1174-8", "title" : "The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "84", "plainTextFormattedCitation" : "84", "previouslyFormattedCitation" : "84" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }84Ynot reported; 20% re-genotyped with 99% concordancegeneral populationgeneral populationSanghera BMC Med Genet 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2350-9-59", "ISSN" : "1471-2350", "PMID" : "18598350", "abstract" : "BACKGROUND: Recent genome-wide association (GWA) studies have identified several unsuspected genes associated with type 2 diabetes (T2D) with previously unknown functions. In this investigation, we have examined the role of 9 most significant SNPs reported in GWA studies: [peroxisome proliferator-activated receptor gamma 2 (PPARG2; rs 1801282); insulin-like growth factor two binding protein 2 (IGF2BP2; rs 4402960); cyclin-dependent kinase 5, a regulatory subunit-associated protein1-like 1 (CDK5; rs7754840); a zinc transporter and member of solute carrier family 30 (SLC30A8; rs13266634); a variant found near cyclin-dependent kinase inhibitor 2A (CDKN2A; rs10811661); hematopoietically expressed homeobox (HHEX; rs 1111875); transcription factor-7-like 2 (TCF7L2; rs 10885409); potassium inwardly rectifying channel subfamily J member 11(KCNJ11; rs 5219); and fat mass obesity-associated gene (FTO; rs 9939609)].\n\nMETHODS: We genotyped these SNPs in a case-control sample of 918 individuals consisting of 532 T2D cases and 386 normal glucose tolerant (NGT) subjects of an Asian Sikh community from North India. We tested the association between T2D and each SNP using unconditional logistic regression before and after adjusting for age, gender, and other covariates. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels using multiple linear regression analysis.\n\nRESULTS: Four of the nine SNPs revealed a significant association with T2D; PPARG2 (Pro12Ala) [odds ratio (OR) 0.12; 95% confidence interval (CI) (0.03-0.52); p = 0.005], IGF2BP2 [OR 1.37; 95% CI (1.04-1.82); p = 0.027], TCF7L2 [OR 1.64; 95% CI (1.20-2.24); p = 0.001] and FTO [OR 1.46; 95% CI (1.11-1.93); p = 0.007] after adjusting for age, sex and BMI. Multiple linear regression analysis revealed significant association of two of nine investigated loci with diabetes-related quantitative traits. The 'C' (risk) allele of CDK5 (rs 7754840) was significantly associated with decreased HDL-cholesterol levels in both NGT (p = 0.005) and combined (NGT and T2D) (0.005) groups. The less common 'C' (risk) allele of TCF7L2 (rs 10885409) was associated with increased LDL-cholesterol (p = 0.010) in NGT and total and LDL-cholesterol levels (p = 0.008; p = 0.003, respectively) in combined cohort.\n\nCONCLUSION: To our knowledge, this is first study reporting the role of some recently emerged loci with T2D in a high risk population of As\u2026", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Shizhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jairup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrell", "given" : "Robert E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nath", "given" : "Swapan K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "Mohammed I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "59", "title" : "Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "94", "plainTextFormattedCitation" : "94", "previouslyFormattedCitation" : "94" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }94YYendogamous Khatri Sikh populationendogamous Khatri Sikh population with no family history of type 2 diabetes; 262 were non-diabetic spousesSanghera Ann Hum Genet 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-1809.2008.00443.x", "ISSN" : "0003-4800", "PMID" : "18397358", "abstract" : "Recently, the transcription factor-7-like 2 (TCF7L2) gene has been identified as the most important type 2 diabetes mellitus (T2DM) susceptibility gene. Common intronic polymorphisms in this gene have been found to be strongly associated with T2DM susceptibility showing marked reproducibility in multiple populations. The purpose of this study was to confirm the reported association of six TCF7L2 variants in a Khatri Sikh diabetic sample from North India. We genotyped six-associated SNPs in a case-control sample consisting of 556 T2DM cases and 537 controls. We also examined the impact of these variants on body mass index (BMI), waist to hip ratio (WHR), fasting insulin, and glucose and lipid levels. We report replication of association of four of the six SNPs with T2DM in this Khatri Sikh sample [rs7903146, (p = 0.010); rs11196205, (p = 0.011); rs10885409, (p = 0.002) and rs4918789, (p = 0.029)], under a dominant model conferring odds ratios (ORs) of 1.39, 1.44, 1.57 and 1.36, respectively. Haplotype analysis provided further evidence of association by showing a significant difference between cases and controls as revealed by the global omnibus test (chi(2)= 19.36; p = 0.0036). Multiple linear regression analysis also revealed the risk allele carriers of three of four significant SNPs (rs7903146, rs11196205, rs10885409) to be significantly associated with increased fasting total cholesterol (p value = 0.019, 0.025, 0.006) and LDL cholesterol levels (p value = 0.021, 0.018, 0.005), respectively. Our findings confirm that the TCF7L2 gene is a major risk factor for development of T2DM in Khatri Sikhs. It also provides new information about the significant impact of TCF7L2 gene variants on plasma cholesterol levels that appear to be independent of BMI.", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nath", "given" : "S K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gambarelli", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim-Howard", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "S K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "G S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "N K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "J J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "M I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of human genetics", "id" : "ITEM-1", "issue" : "Pt 4", "issued" : { "date-parts" : [ [ "2008", "7" ] ] }, "page" : "499-509", "title" : "TCF7L2 polymorphisms are associated with type 2 diabetes in Khatri Sikhs from North India: genetic variation affects lipid levels.", "type" : "article-journal", "volume" : "72" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "238", "plainTextFormattedCitation" : "238", "previouslyFormattedCitation" : "238" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }238YYendogamous Khatri Sikh populationendogamous Khatri Sikh population with no family history of type 2 diabetes; 262 were non-diabetic spousesRees BMC Med Genet 2008 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2350-9-8", "ISSN" : "1471-2350", "PMID" : "18291022", "abstract" : "BACKGROUND: Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry.\n\nMETHODS: We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects.\n\nRESULTS: The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 - 1.56, p = 1.96 x 10(-3)). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p < or= 1.04 x 10(-7)).\n\nCONCLUSION: Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellary", "given" : "Srikanth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Britten", "given" : "Abigail C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "8", "title" : "Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "239", "plainTextFormattedCitation" : "239", "previouslyFormattedCitation" : "239" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }239YYnot specifiedsame geographical areas through community screeningSanghera J Human Genet 2009 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/jhg.2009.7", "ISSN" : "1435-232X", "PMID" : "19247373", "abstract" : "A recent meta-analysis on three genome-wide association (GWA) scans identified six loci (NOTCH2, THADA, ADAMTS9, JAZF1, CDC123/CAMKID and TSPAN8/LGRS) highly associated with type II diabetes (T2D) in Caucasians. This investigation seeks to confirm this association with diabetes and related metabolic traits in Khatri Sikh diabetics of North India. We genotyped highly significant variants from each locus in a case-control cohort consisting of 680 T2D cases and 637 normoglycemic (NG) controls. Only CDC123/CAMKID (rs12779790) replicated earlier evidence of association with T2D under a dominant model (odds ratio (OR): 1.27; 95% confidence interval (CI): 1.02-1.57; P=0.031) during initial testing. However, we could not confirm this association using multiple testing corrections. In a multiple linear-regression analysis, the same variant in the CDC123/CAMKID revealed a marked decrease in fasting insulin levels among 'G' (risk) allele carriers independently in NG controls (P=0.030) and in T2D cases (P=0.009), as well as in the combined sample (P=0.003) after adjusting for covariates. Evidence of impaired beta-cell function was also observed among 'G' (risk) allele carriers in T2D cases (P=0.008) and in a combined cohort (P=0.026). Our data could not confirm the role of the remaining variants with risk either for T2D or quantitative phenotypes measuring insulin secretion or insulin resistance. These findings suggest that CDC123/CAMKID could be a major risk factor for the development of T2D in Sikhs by affecting beta-cell function. To our knowledge, this is the first study reporting the role of recently emerging loci in this high-risk population from the South Asian subcontinent.", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aston", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "3" ] ] }, "page" : "162-8", "title" : "Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "240", "plainTextFormattedCitation" : "240", "previouslyFormattedCitation" : "240" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }240YYendogamous Khatri Sikh populationendogamous Khatri Sikh population with no family history of type 2 diabetes; 262 were non-diabetic spousesYajnik Diabetologia 2009 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-008-1186-6", "ISSN" : "1432-0428", "PMID" : "19005641", "abstract" : "AIMS AND HYPOTHESIS: Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune.\n\nMETHODS: We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India.\n\nRESULTS: We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13-1.40; p = 3 x 10(-5)). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01-0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09-0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06-1.37; p = 4.0 x 10(-3)), and also for waist circumference and other anthropometric variables.\n\nCONCLUSIONS: Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freathy", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mani", "given" : "K R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kale", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deshpande", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Krishnaveni", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Veena", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fall", "given" : "C H D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "M I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "A T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "2" ] ] }, "page" : "247-52", "title" : "FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "90", "plainTextFormattedCitation" : "90", "previouslyFormattedCitation" : "90" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }90Ynot reportedrecruited from Diabetes Clinic of the King EdwardMemorial Hospital and Research Centre in Puneparents of children in the Pune Maternal Nutrition Study from urban and rural regions, parents in Pune Children Study, and Coronary Risk of Insulin Sensitivity in Indian Subjects studyHaseeb J Biosci 2009 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0973-7138", "PMID" : "19805902", "abstract" : "Studies on the association of the Pro12Ala and C1431T polymorphisms of PPAR? with diabetes and obesity have revealed extensive population-dependent variations. However, association of these polymorphisms with the metabolic syndrome and its individual components has not been well investigated in the Indian population. The Indian population harbours the maximum number of diabetics in the world who are thus more susceptible to metabolic disorders. We screened a South Indian population (N=699) for a possible association of these polymorphisms with the metabolic syndrome (MS) and type 2 diabetes. We also investigated the correlation of these two single-nucleotide polymorphisms (SNPs) with plasma resistin levels. The C1431T SNP was associated with higher levels of plasma resistin (P=0.017). Furthermore, C1431T was associated with resistin in different tertiles. Prevalence of the 'Pro-C' haplotype decreased with increasing tertiles of resistin (84.1% to 75.4%, P=0.037). Plasma resistin levels were not found to be associated with MS and type 2 diabetes. These results point to a likely association of plasma resistin levels with PPAR? polymorphisms in the Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Haseeb", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iliyas", "given" : "Mohammad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakrabarti", "given" : "Subhabrata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqui", "given" : "Arif A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naik", "given" : "Sudhir R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Sudip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suragani", "given" : "Madhuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehtesham", "given" : "Nasreen Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of biosciences", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "405-14", "title" : "Single-nucleotide polymorphisms in peroxisome proliferator-activated receptor gamma and their association with plasma levels of resistin and the metabolic syndrome in a South Indian population.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "75", "plainTextFormattedCitation" : "75", "previouslyFormattedCitation" : "75" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }75Ynot reported; subset re-genotypedrecruited from Mediciti hospitalrecruited from Mediciti hospitalChauhan Diabetes 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db09-1386", "ISSN" : "1939-327X", "PMID" : "20424228", "abstract" : "OBJECTIVE: Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control studies.\n\nRESEARCH DESIGN AND METHODS: We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects.\n\nRESULTS: We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 x 10(-3) to 4.6 x 10(-34)). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71-2.09], P = 4.6 x 10(-34)). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of beta-cell function (P = 6.9 x 10(-8) and 3 x 10(-4), respectively), which looked consistent with recessive and under-dominant models, respectively.\n\nCONCLUSIONS: Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.", "author" : [ { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spurgeon", "given" : "Charles J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "Seema", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "Smita R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "M V Kranthi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prakash", "given" : "Swami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "Chittaranjan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "Giriraj R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2010", "8" ] ] }, "page" : "2068-74", "title" : "Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "92", "plainTextFormattedCitation" : "92", "previouslyFormattedCitation" : "92" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }92Y>90%, 10% with concordance of 99.7%Delhi: consecutively recruited from the Endocrinology clinic of All India Institute of Medical Sciences; Pune: general population in Pune and surrounding areasDelhi: urban dwellers of Indo-European ethnicity with no family history of diabetes in ?rst and/or second degree relatives; Pune: parents of children in the Pune Maternal Nutrition Study and Coronary Risk of Insulin Sensitivity in Indian Subjects studyGupta Ann Hum Genet 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1469-1809.2010.00580.x", "ISSN" : "1469-1809", "PMID" : "20597906", "abstract" : "The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18-clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan-based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p-value = 0.00191; p-value = 0.00179, respectively), and odds ratios of 2.1 (dominant-model) and 2.0 (recessive-model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist-Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single-SNP, combined-SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally-learned sedentary lifestyle and fat-enriched dietary habits, WHR rather than body-mass-index emerged as a robust predictor of risk for T2D in this population.", "author" : [ { "dropping-particle" : "", "family" : "Gupta", "given" : "Vipin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khadgawat", "given" : "Rajesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Hon Keung Tony", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Satish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Ajay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "Vadlamudi Raghavendra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sachdeva", "given" : "M P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of human genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "361-8", "title" : "A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India.", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "91", "plainTextFormattedCitation" : "91", "previouslyFormattedCitation" : "91" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }91Ynot reportedAggarwal population (60% had family history of type 2 diabetes)same geographic region as casesChidambaram Metabolism 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2010.04.024", "ISSN" : "1532-8600", "PMID" : "20580033", "abstract" : "Recent genomewide association studies have identified several new gene variants associated with type 2 diabetes mellitus (T2D) mostly in European populations. These need to be replicated in other populations. We studied 926 unrelated T2D and 812 normal glucose-tolerant subjects randomly selected from the Chennai Urban Rural Epidemiology Study in Southern India. A total of 45 single nucleotide polymorphisms (SNPs) from 15 genes and 13 unannotated loci identified from recent genomewide association T2D studies were genotyped. Only 6 of 45 SNPs studied were replicated in this South Indian population. Three SNPs-rs7756992 (P = .007), rs7754840 (P = .015), and rs6931514 (P = .029)-of the CDKAL1, rs7020996 (P = .003) of the CDKN2A/B gene, rs7923837 (P = .038) of the HHEX gene, and rs12056034 (P = .033) of the BAZ1B gene were associated with T2D in our population. Large-scale studies are needed in our population to validate our findings.", "author" : [ { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2010", "12" ] ] }, "page" : "1760-6", "title" : "Replication of recently described type 2 diabetes gene variants in a South Indian population.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "78", "plainTextFormattedCitation" : "78", "previouslyFormattedCitation" : "78" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }78Ynot reported; 20% re-genotyped with 99.6% concordancegeneral populationgeneral populationMukhopadhyaya Genet Mol Res 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.4238/vol9-4gmr883", "ISSN" : "1676-5680", "PMID" : "20967696", "abstract" : "A population-based study was undertaken to evaluate linkage between single-nucleotide polymorphisms known as risk factors and type 2 diabetes in an Indian population. The study population was comprised of 40 normal glucose-tolerant individuals (21 males and 19 females) and 40 type 2 diabetes patients (21 males and 19 females). The genes and their corresponding single-nucleotide polymorphisms that we screened were VDR (rs 731236 and rs 1544410), IL-6 (rs 1800795), TCF7L2 (rs 7903146) and TNF-\u03b1 (rs 1800629). The risk alleles were more frequent in the subjects with type 2 diabetes, except for the TNF-\u03b1 gene, which was very infrequent in the population; the normal allele occurred at high and similar frequencies in both normal and diabetic individuals.", "author" : [ { "dropping-particle" : "", "family" : "Mukhopadhyaya", "given" : "P N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Acharya", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavan", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purohit", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mutha", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetics and molecular research : GMR", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "2060-8", "title" : "Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in an Indian population.", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "79", "plainTextFormattedCitation" : "79", "previouslyFormattedCitation" : "79" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }79YYpre-specified sub-populationsame population as casesSanghera Metabolism 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2009.07.043", "ISSN" : "1532-8600", "PMID" : "19846176", "abstract" : "We have examined the association of 14 tagging single nucleotide polymorphisms (tagSNPs) in peroxisome proliferator activated receptor-gamma transcripts 1 and 2 (PPARG1 and 2) and 5 tagSNPs in adiponectin (ADIPOQ) genes for their effect on type 2 diabetes mellitus (T2D) risk in Asian Indian Sikhs. A total of 554 T2D cases and 527 normoglycemic controls were examined for association with T2D and other subphenotypes of T2D. With the exception of a strong association of PPARG2/Pro12Ala with T2D (odds ratio, 0.13; 95% confidence interval, 0.03-0.56; P = .0007), no other tagSNP in the PPARG locus revealed any significant association with T2D in this population. Similarly, none of the tagSNPs in the ADIPOQ gene was associated with T2D susceptibility in single-site analysis. However, haplotype analysis provided strong evidence of association of these loci with T2D. Three-site haplotype analysis in the PPARG locus using the 2 marginally associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala (P/rs1801282) revealed a strong association of 1 \"risk\" (CGC) (P = .003, permutation P = .015) and 1 \"protective\" (CAC) (P = .001, permutation P = .005) haplotype associated with T2D. However, the major effect still appears to be driven by Pro12Ala, as the association of these haplotypes did not remain significant when analyzed conditional upon Pro12Ala (P = .262). In addition, 2-site haplotype analysis in the ADIPOQ locus using only 2 marginally associated SNPs (AD/rs182052 and AD/rs7649121) revealed a significant protective association of the GA haplotype with T2D (P = .009, permutation P = .026). Multiple linear regression analysis also revealed significant association of an ADIPOQ variant (AD/rs12495941) with total body weight (P = .010), waist (P = .024), and hip (P = .021), although these associations were not significant after adjusting for multiple testing. Our new findings strongly suggest that the genetic variation in PPARG and ADIPOQ loci could contribute to the risk for the development of T2D in Indian Sikhs. Identification of causal SNPs in these important biological and positional candidate genes would help determine the true physiologic significance of these loci in T2D and obesity.", "author" : [ { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir Kaur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demirci", "given" : "Fatma Yesim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "Lyda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet Singh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder Kumar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jairup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aston", "given" : "Christopher Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "Ilyas Mohammad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "492-501", "title" : "PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "241", "plainTextFormattedCitation" : "241", "previouslyFormattedCitation" : "241" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }241YYendogamous Khatri Sikh populationendogamous Khatri Sikh population with no family history of type 2 diabetes; 262 were non-diabetic spousesVimaleswaran Met Clin Exp 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.metabol.2009.07.034", "ISSN" : "1532-8600", "PMID" : "19846173", "abstract" : "Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone receptor of ligand-dependent transcription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and its related traits in a South Indian population. The study subjects (1000 type 2 diabetes mellitus and 1000 normal-glucose-tolerant subjects) were chosen randomly from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The variants were screened by single-stranded conformational variant, direct sequencing, and restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. The -1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio, 2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of 12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The 3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His) haplotype was associated with a reduced risk of type 2 diabetes mellitus (P < .0001). Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Vimaleswaran", "given" : "Karani S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jayapriya", "given" : "Munuguru Gopal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Majumder", "given" : "Partha P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rao", "given" : "M R Sathyanarayana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Metabolism: clinical and experimental", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "457-62", "title" : "Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population.", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "242", "plainTextFormattedCitation" : "242", "previouslyFormattedCitation" : "242" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }242Ynot reported; 20% re-genotyped with 100% concordancegeneral populationgeneral populationTan J Clin End 2010 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2009-0688", "ISSN" : "1945-7197", "PMID" : "19892838", "abstract" : "CONTEXT: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized.\n\nOBJECTIVE: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. Design: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians.\n\nRESULTS: In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.\n\nCONCLUSIONS: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.", "author" : [ { "dropping-particle" : "", "family" : "Tan", "given" : "Jonathan T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel P K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nurbaya", "given" : "Siti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Xiu Li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leong", "given" : "Helen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seet", "given" : "Lin Tze", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siew", "given" : "Wei Fong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kon", "given" : "Winston", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saw", "given" : "Seang Mei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jeannette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chew", "given" : "Suok Kai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "390-7", "title" : "Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore.", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "86", "plainTextFormattedCitation" : "86", "previouslyFormattedCitation" : "86" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }86Y (rs2237892 and rs2237897 deviated from HWE p<0.01)>90% call rate; 30 samples re-genotyped with 100% concordanceSDCS: recruited from Singapore National Healthcare Group Polyclinics; NHS98: general populationNHS98: general populationRees Diabet Med 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1464-5491.2011.03257.x", "ISSN" : "1464-5491", "PMID" : "21294771", "abstract" : "AIMS: A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians.\n\nMETHODS: We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged \u226540 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies.\n\nRESULTS: In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95%CI 0.24-0.67) kg/m(2) per A-allele (P=3.0 \u00d7 10(-5) ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P=0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95%CI) 1.18 (1.07-1.30); P=0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95%CI 1.14-1.31); P=1.07 \u00d7 10(-8) ] even after adjusting for BMI [1.18 (95%CI 1.10-1.27); P=1.02 \u00d7 10(-5) ] or waist circumference [1.18 (95%CI 1.10-1.27); P=3.97 \u00d7 10(-5) ].\n\nCONCLUSIONS: The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaudhary", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellary", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashmi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chaturvedi", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "T H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "673-80", "title" : "An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference.", "type" : "article-journal", "volume" : "28" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "83", "plainTextFormattedCitation" : "83", "previouslyFormattedCitation" : "83" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }83YYCobra: community sampling; UKADS: not specified; DGP: hospitals in MirpurCobra: community sampling; UKADS: same geographic region; DGP: community screeningRees PloS One 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0024710", "ISSN" : "1932-6203", "PMID" : "21949744", "abstract" : "BACKGROUND: The Meta-Analysis of Glucose and Insulin related traits Consortium (MAGIC) recently identified 16 loci robustly associated with fasting glucose, some of which were also associated with type 2 diabetes. The purpose of our study was to explore the role of these variants in South Asian populations of Punjabi ancestry, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: Sixteen single nucleotide polymorphisms (SNPs) were genotyped in 1678 subjects with type 2 diabetes and 1584 normoglycaemic controls from two Punjabi populations; one resident in the UK and one indigenous to the District of Mirpur. In the normoglycaemic controls investigated for fasting glucose associations, 12 of 16 SNPs displayed \u03b2 values with the same direction of effect as that seen in European studies, although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose (\u03b2\u200a=\u200a0.063 [95% CI: 0.013, 0.113] p\u200a=\u200a0.015). Of interest, the MTNR1B rs10830963 SNP displayed a negative \u03b2 value for fasting glucose in our study; this effect size was significantly lower than that seen in Europeans (p\u200a=\u200a1.29\u00d710(-4)). In addition to previously reported type 2 diabetes risk variants in TCF7L2 and SLC30A8, SNPs in ADCY5 (rs11708067) and GLIS3 (rs7034200) displayed evidence for association with type 2 diabetes, with odds ratios of 1.23 (95% CI: 1.09, 1.39; p\u200a=\u200a9.1\u00d710(-4)) and 1.16 (95% CI: 1.05, 1.29; p\u200a=\u200a3.49\u00d710(-3)) respectively.\n\nCONCLUSIONS/SIGNIFICANCE: Although only the SLC30A8 rs11558471 SNP was nominally associated with fasting glucose in our study, the finding that 12 out of 16 SNPs displayed a direction of effect consistent with European studies suggests that a number of these variants may contribute to fasting glucose variation in individuals of South Asian ancestry. We also provide evidence for the first time in South Asians that alleles of SNPs in GLIS3 and ADCY5 may confer risk of type 2 diabetes.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "Sudhesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "e24710", "publisher" : "Public Library of Science", "title" : "Effects of 16 genetic variants on fasting glucose and type 2 diabetes in South Asians: ADCY5 and GLIS3 variants may predispose to type 2 diabetes.", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "112", "plainTextFormattedCitation" : "112", "previouslyFormattedCitation" : "112" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }112YYUKADS: not specified; DGP: hospitals in MirpurUKADS: same geographic region; DGP: community screeningChavali J Human Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/jhg.2011.83", "ISSN" : "1435-232X", "PMID" : "21814221", "abstract" : "Variants in genes involved in pancreatic \u03b2-cell development and function are known to cause monogenic forms of type 2 diabetes and are also associated with complex form. In this study, we studied the genetic association of polymorphisms in such important genes with type 2 diabetes in the high-risk Indians. We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. HNF4A promoter P2 polymorphisms rs1884613 and rs2144908, which are in high linkage disequilibrium, showed significant association with type 2 diabetes (odds ratio (OR)=1.37 (95% confidence interval (CI) 1.19-1.57), P=9.4 \u00d7 10(-6) for rs1884613 and OR=1.37 (95%CI 1.20-1.57), P=6.0 \u00d7 10(-6) for rs2144908), as previously shown in other populations. We observed body mass index-dependent association of these variants with type 2 diabetes in normal-weight/lean subjects. Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 \u00d7 10(-4)). Thus, pancreatic \u03b2-cell development and function genes contribute to susceptibility to type 2 diabetes in North Indians.", "author" : [ { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of human genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10", "4" ] ] }, "language" : "en", "page" : "695-700", "publisher" : "Nature Publishing Group", "title" : "Association of variants in genes involved in pancreatic \u03b2-cell development and function with type 2 diabetes in North Indians.", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "243", "plainTextFormattedCitation" : "243", "previouslyFormattedCitation" : "243" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }243YYconsecutively recruited from the Endocrinology clinic of All India Institute of Medical Sciencesurban dwellers of Indo-European ethnicity with no family history of diabetes in ?rst and/or second degree relativesBoodram West Indian Med J 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0043-3144", "PMID" : "22512215", "abstract" : "OBJECTIVE: To examine the effect of genetic variation in KCNJ11 on the risk of Type 2 diabetes mellitus in Trinidadians.\n\nMETHODS: The coding and bordering intron-exon regions of the KCNJ11 gene were sequenced in 168 diabetic and 61 non-diabetic subjects who historically were thought to be of South Asian Indian ancestry as well as 66 diabetic and 59 non-diabetic subjects of African ancestry. Allele and haplotype frequency differences were calculated between cases and controls and linkage equilibrium was assessed across the KCNJ11 region.\n\nRESULTS: We identified novel missense mutations in both subject groups including A94P and R369C in a diabetic Indo-Trinidadian subject, S113G in a non-diabetic Indo-Trinidadian subject, and S118L in a diabetic Afro-Trinidadian subject. It is unknown if these mutations are pathogenic as other family members were not available for study. Additionally, the common variant E23K was associated with Type 2 diabetes in the Indo-Trinidadian group (OR = 1.797 [1.148-2.814], p = 0.0098).\n\nCONCLUSIONS: Rare variants in KCNJ11 are segregating in the Indo- and Afro-Trinidadian populations and further studies are needed to determine their contribution, if any, to the overall prevalence of diabetes in these groups. Common variants such as E23K may increase the risk in the Indo-Trinidadian population.", "author" : [ { "dropping-particle" : "", "family" : "Boodram", "given" : "L G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miyake", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayes", "given" : "M G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bell", "given" : "G I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cockburn", "given" : "B N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The West Indian medical journal", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "604-7", "title" : "Association of the KCNJ11 variant E23K with type 2 diabetes in Indo-Trinidadians.", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "89", "plainTextFormattedCitation" : "89", "previouslyFormattedCitation" : "89" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }89Ynot reportedrecruited from diabetic outpatient clinicsrecruited from Chest Clinic at Mt. Hope Hospital (Champs Fleurs, Trinidad and Tobago) and from San Fernando General HospitalRees Diabetologia 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-011-2063-2", "ISSN" : "1432-0428", "PMID" : "21350842", "abstract" : "AIMS/HYPOTHESIS: Recent genome-wide association (GWA) studies and subsequent replication studies have greatly increased the number of validated type 2 diabetes susceptibility variants, but most of these have been conducted in European populations. Despite the high prevalence of the disease in South Asians, studies investigating GWA-validated type 2 diabetes risk variants in this ethnic group are limited. We investigated 30 single nucleotide polymorphisms (SNPs), predominantly derived from recent GWA studies, to determine if and to what extent these variants affect type 2 diabetes risk in two Punjabi populations, originating predominantly from the District of Mirpur, Pakistan.\n\nMETHODS: Thirty SNPs were genotyped in 1,678 participants with type 2 diabetes and 1,584 normoglycaemic control participants from two populations; one resident in the UK and one indigenous to the District of Mirpur.\n\nRESULTS: SNPs in or near PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2, SLC30A8, KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 displayed significant (p < 0.05) associations with type 2 diabetes, with similar effect sizes to those seen in European populations. A constructed genetic risk score was associated with type 2 diabetes (p = 5.46 \u00d7 10(-12)), BMI (p = 2.25 \u00d7 10(-4)) and age at onset of diabetes (p = 0.002).\n\nCONCLUSIONS/INTERPRETATION: We have demonstrated that 13 variants confer an increased risk of type 2 diabetes in our Pakistani populations; to our knowledge this is the first time that SNPs in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 have been significantly associated with the disease in South Asians. Large-scale studies and meta-analyses of South Asian populations are needed to further confirm the effect of these variants in this ethnic group.", "author" : [ { "dropping-particle" : "", "family" : "Rees", "given" : "S D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "M Z I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Hare", "given" : "J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "1368-74", "title" : "Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations.", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "81", "plainTextFormattedCitation" : "81", "previouslyFormattedCitation" : "81" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }81YYUKADS: not specified; DGP: hospitals in MirpurUKADS: same geographic region; DGP: community screeningSim PLoS Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1001363", "ISSN" : "1553-7404", "PMID" : "21490949", "abstract" : "Recent large genome-wide association studies (GWAS) have identified multiple loci which harbor genetic variants associated with type 2 diabetes mellitus (T2D), many of which encode proteins not previously suspected to be involved in the pathogenesis of T2D. Most GWAS for T2D have focused on populations of European descent, and GWAS conducted in other populations with different ancestry offer a unique opportunity to study the genetic architecture of T2D. We performed genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945 controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians (977 cases, 1,169 controls). In addition to the search for novel variants implicated in T2D, these multi-ethnic cohorts serve to assess the transferability and relevance of the previous findings from European descent populations in the three major ethnic populations of Asia, comprising half of the world's population. Of the SNPs associated with T2D in previous GWAS, only variants at CDKAL1 and HHEX/IDE/KIF11 showed the strongest association with T2D in the meta-analysis including all three ethnic groups. However, consistent direction of effect was observed for many of the other SNPs in our study and in those carried out in European populations. Close examination of the associations at both the CDKAL1 and HHEX/IDE/KIF11 loci provided some evidence of locus and allelic heterogeneity in relation to the associations with T2D. We also detected variation in linkage disequilibrium between populations for most of these loci that have been previously identified. These factors, combined with limited statistical power, may contribute to the failure to detect associations across populations of diverse ethnicity. These findings highlight the value of surveying across diverse racial/ethnic groups towards the fine-mapping efforts for the casual variants and also of the search for variants, which may be population-specific.", "author" : [ { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Rick Twee-Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tay", "given" : "Wan-Ting", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik-Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E-Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS genetics", "editor" : [ { "dropping-particle" : "", "family" : "Gibson", "given" : "Greg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "4" ] ] }, "page" : "e1001363", "publisher" : "Public Library of Science", "title" : "Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "74", "plainTextFormattedCitation" : "74", "previouslyFormattedCitation" : "74" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }74YYrandomly sampled from general populationrandomly sampled from general populationChauhan J Hum Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/jhg.2011.87", "ISSN" : "1435-232X", "PMID" : "21814223", "abstract" : "Common variants of fat mass and obesity-associated gene (FTO, fat mass- and obesity-associated gene) have been shown to be associated with obesity and type 2 diabetes in population of European and non-European ethnicity. However, studies in Indian population have provided inconsistent results. Here, we examined association of eight FTO variants (rs1421085, rs8050136, rs9939609, rs9930506, rs1861867, rs9926180, rs2540769 and rs708277) with obesity and type 2 diabetes in 5364 North Indians (2474 type 2 diabetes patients and 2890 non-diabetic controls) in two stages. None of the variants including previously reported intron 1 variants (rs1421085, rs8050136, rs9939609 and rs9930506) showed body mass index (BMI)-dependent/independent association with type 2 diabetes. However, rs1421085, rs8050136 and rs9939609 were associated with obesity status and measures of obesity (BMI, waist circumference and waist-to-hip ratio) in stage 2 and combined study population. Meta-analysis of the two study population results also revealed that rs1421085, rs8050136 and rs9939609 were significantly associated with BMI both under the random- and fixed-effect models (P (random/fixed)=0.02/0.0001, 0.004/0.0006 and 0.01/0.01, respectively). In conclusion, common variants of FTO were associated with obesity, but not with type 2 diabetes in North Indian population.", "author" : [ { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahendran", "given" : "Yuvaraj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nigam", "given" : "Shubhanchi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubey", "given" : "Himanshu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Varma", "given" : "Binuja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of human genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "720-6", "publisher" : "The Japan Society of Human Genetics", "title" : "Common variants of FTO and the risk of obesity and type 2 diabetes in Indians.", "title-short" : "J Hum Genet", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "93", "plainTextFormattedCitation" : "93", "previouslyFormattedCitation" : "93" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }93Y>90%, 5% with concordance of 99.99%consecutively recruited from the Endocrinology clinic of All India Institute of Medical Sciencesrecruited from diabetes awareness campsAnuradha Clin Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1399-0004.2010.01577.x", "ISSN" : "1399-0004", "PMID" : "21062274", "abstract" : "Variants in hepatocyte nuclear factor 4A (HNF4A) cause maturity onset diabetes of the young (MODY 1). The objective of the study was to screen the coding and the promoter regions of HNF4A mutations in 87 unrelated South Indian subjects with clinically diagnosed MODY with severe forms of diabetes referred to a tertiary diabetes centre. In addition, we looked at the association of common polymorphisms in HNF4 A gene in subjects with MODY (n = 199), early onset type 2 diabetes (T2DM) (n = 505), late onset T2DM (n = 287) and normal glucose tolerance (NGT) (n = 247). We identified three novel mutations in the P2 promoter region of HNF4A, namely -1009 G/C, -129 T/C and -79 C/T. Co-segregation with diabetes was noted with the -1009 G/C and -129 T/C in one MODY family. We also studied eight single nucleotide polymorphisms (SNPs) of HNF4A gene. The frequency of the minor allele of the rs2144908 was significantly higher in subjects with MODY (p < 0.01) and that of rs736823 was significantly higher in early onset T2DM (p = 0.001). Minor allele frequency of rs1884614 and rs2071197 was significantly lower in early onset T2DM when compared to NGT subjects (p < 0.01). Minor allele frequency of Val255Met was significantly lower in MODY, early onset T2DM and late onset T2DM compared to NGT subjects (p < 0.01). This is the first report of MODY 1 mutations from India and shows that 3.4% of clinically diagnosed MODY subjects have MODY 1. In addition, we report SNPs of HNF4A that are both susceptible to, and protective against, MODY and early onset T2DM.", "author" : [ { "dropping-particle" : "", "family" : "Anuradha", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical genetics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "541-9", "title" : "Association of novel variants in the hepatocyte nuclear factor 4A gene with maturity onset diabetes of the young and early onset type 2 diabetes.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "76", "plainTextFormattedCitation" : "76", "previouslyFormattedCitation" : "76" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }76Ynot reported; 20% re-genotyped with 99% concordancegeneral populationgeneral populationKooner Nat Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.921", "ISSN" : "1546-1718", "PMID" : "21874001", "abstract" : "We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 \u00d7 10(-8) to P = 1.9 \u00d7 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 \u00d7 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.", "author" : [ { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehmi", "given" : "Joban", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Weihua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chia", "given" : "Kee-Seng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimas", "given" : "Antigone S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jafar", "given" : "Tazeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jowett", "given" : "Jeremy B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Xinzhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Fumihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aung", "given" : "Tin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Das", "given" : "Debashish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grundberg", "given" : "Elin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedman", "given" : "Asa K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hydrie", "given" : "Zafar I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Islam", "given" : "Muhammed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khor", "given" : "Chiea-Chuen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kowlessur", "given" : "Sudhir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristensen", "given" : "Malene M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Wei-Yen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nica", "given" : "Alexandra C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinidiyapathirage", "given" : "Janani M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samuel", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Nabi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shera", "given" : "A Samad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Small", "given" : "Kerrin S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suo", "given" : "Chen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wickremasinghe", "given" : "Ananda R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Mingyu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Fan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Goncalo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kato", "given" : "Norihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Junbin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seielstad", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zimmet", "given" : "Paul Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Yik Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "984-9", "title" : "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "71", "plainTextFormattedCitation" : "71", "previouslyFormattedCitation" : "71" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }71YYLOLIPOP: recruited from lists of GPs in West London; PROMIS: out-patient departments; SINDI: general population; COBRA: general population; DGP: hospitals or Diabetes awareness camps; CURES: general population; Mauritius cohort: population based survey; RHS: population based survey used to participate in study; SDS: endogamous Khatri Sikh population; SCCS: recruited from hospitals and polyclinicsLOLIPOP: recruited from lists of GPs in West London; PROMIS: matched cases from visitors in out-patient; SINDI: general population; COBRA: general population; DGP: recruited from community screening camps; CURES: random sampling from general population; Mauritius cohort: population based survey; RHS: population based survey; SDS: endogamous Khatri Sikh population with no family history of type 2 diabetes, 262 were non-diabetic spouses; SCCS: general populationBeen BMC Med Genet 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/1471-2350-12-18", "ISSN" : "1471-2350", "PMID" : "21261977", "abstract" : "BACKGROUND: Polymorphisms in intron 15 of potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) gene have been associated with type II diabetes (T2D) in Japanese genome-wide association studies (GWAS). More recently a meta-analysis of European GWAS has detected a new independent signal associated with T2D in intron 11 of the KCNQ1 gene. The purpose of this investigation is to examine the role of these variants with T2D in populations of Asian Indian descent from India and the US.\n\nMETHODS: We examined the association between four variants in the KCNQ1 gene with T2D and related quantitative traits in a total of 3,310 Asian Indian participants from two different cohorts comprising 2,431 individuals of the Punjabi case-control cohort from the Sikh Diabetes Study and 879 migrant Asian Indians living in the US.\n\nRESULTS: Our data confirmed the association of a new signal at the KCNQ1 locus (rs231362) with T2D showing an allelic odds ratio (OR) of 1.24 95%CI [1.08-1.43], p = 0.002 in the Punjabi cohort. A moderate association with T2D was also seen for rs2237895 in the Punjabi (OR 1.14; p = 0.036) and combined cohorts (meta-analysis OR 1.14; p = 0.018). Three-site haplotype analysis of rs231362, rs2237892, rs2237895 exhibited considerably stronger evidence of association of the GCC haplotype with T2D showing OR of 1.24 95%CI [1.00-1.53], p = 0.001, permutation p = 8 \u00d7 10-4 in combined cohorts. The 'C' risk allele carriers of rs2237895 had significantly reduced measures of HOMA-B in the US cohort (p = 0.008) as well as in combined cohort in meta-analysis (p = 0.009).\n\nCONCLUSIONS: Our investigation has confirmed that the variation within the KCNQ1 locus confers a significant risk to T2D among Asian Indians. Haplotype analysis further suggested that the T2D risk associated with KCNQ1 SNPs may be derived from 'G' allele of rs231362 and 'C' allele of rs2237895 and this appears to be mediated through \u03b2 cell function.", "author" : [ { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "JaiRup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aston", "given" : "Christopher E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC medical genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "18", "title" : "Variants in KCNQ1 increase type II diabetes susceptibility in South Asians: a study of 3,310 subjects from India and the US.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "244", "plainTextFormattedCitation" : "244", "previouslyFormattedCitation" : "244" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }244YYSDS: endogamous Khatri Sikh population; US cohort: not specifiedSDS: endogamous Khatri Sikh population with no family history of type 2 diabetes, 262 were non-diabetic spouses; US cohort: public advertisement for free health screeningRamya Diabetes Technol Ther 2011 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1089/dia.2010.0071", "ISSN" : "1557-8593", "PMID" : "21175269", "abstract" : "AIM: the present study investigated the association of six variants-rs9940128, rs7193144, and rs8050136 (in intron 1), rs918031 and rs1588413 (in intron 8), and rs11076023 (3' untranslated region)-across three regulatory regions of the fat mass and obesity-associated (FTO) gene with obesity and type 2 diabetes mellitus (T2DM) in a South Indian population.\n\nMETHODS: unrelated study subjects (n\u2009=\u20091,852; 1,001 normal glucose-tolerant [NGT] controls and 851 cases [T2DM]) were randomly selected from the Chennai Urban Rural Epidemiological Study (CURES). Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism method, and 20% of samples were sequenced to validate the genotypes obtained. Haplotype analysis was also carried out.\n\nRESULTS: the three polymorphisms rs9940128 A/G, rs1588413 C/T, and rs11076023 A/T of the FTO gene were associated with T2DM in our study population. The rs8050136 C/A variant was associated with obesity, and its association with T2DM was also mediated through obesity. The rs1588413 C/T variant showed an association with obesity in the total study subjects, but when the NGT subjects alone were analyzed, the association with obesity was lost. The haplotype ACCTCT confers a lower risk of T2DM in this South Indian population.\n\nCONCLUSIONS: among South Indians, the rs9940128 A/G, rs11076023 A/T, and rs1588413 C/T variants of the FTO gene were associated with T2DM, whereas the rs8050136 C/A variant was associated with obesity.", "author" : [ { "dropping-particle" : "", "family" : "Ramya", "given" : "Kandaswamy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Majumder", "given" : "Partha P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes technology & therapeutics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "33-42", "title" : "Genetic variations in the FTO gene are associated with type 2 diabetes and obesity in south Indians (CURES-79).", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "245", "plainTextFormattedCitation" : "245", "previouslyFormattedCitation" : "245" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }245Ynot reported; 20% re-genotyped with 99% concordancegeneral populationgeneral populationJanipali Diabetic Med 2012 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1464-5491.2011.03438.x", "ISSN" : "1464-5491", "PMID" : "21913964", "abstract" : "AIMS: Recent genome-wide association studies have identified several Type 2 diabetes-related loci. We investigated the effect of susceptibility genetic variants, individually, together and in combination with conventional risk factors, on Type 2 diabetes and diabetes-related traits in Indians.\n\nMETHODS: We genotyped 33 variants in 1808 Indian patients and 1549 control subjects and performed association analyses with Type 2 diabetes and related traits using an additive model for individual variant and for genetic risk score based on 32 polymorphisms. The discriminatory value of genetic risk over conventional risk factors was analysed using receiver-operating characteristics curve analysis.\n\nRESULTS: The allelic odds ratio ranged from 1.01 (95% CI 0.85-1.19) to 1.66 (95% CI 1.32-2.01) for single-variant analyses. Although, only 16 variants had significant odds ratios, the direction of association for others was similar to earlier reports. The odds ratio for Type 2 diabetes at each genetic risk score point was 1.11 (95% CI 1.09-1.14; P = 5.6 \u00d7 10(-17)) and individuals with extremes of genetic risk score (\u2265 29.0 and \u2264 17.0) had a 7.5-fold difference in risk of Type 2 diabetes. The discrimination rate between control subjects and patients improved marginally on addition of genetic risk score to conventional risk factors (area under curve = 0.959 and 0.963, respectively; P = 0.001). Of all the quantitative traits analysed, MC4R variants showed strong association with BMI (P = 4.1 \u00d7 10(-4)), fat mass per cent (P = 2.4 \u00d7 10(-4)) and other obesity-related traits, including waist circumference and hip circumference (P = 2.0 \u00d7 10(-3) for both), as well as insulin resistance (P =0.02).\n\nCONCLUSIONS: We replicated the association of well-established common variants with Type 2 diabetes in Indians and observed a similar association as reported in Western populations. Combined analysis of 32 variants aids identification of subgroups at increased risk of Type 2 diabetes, but adds only a minor advantage over conventional risk factors.", "author" : [ { "dropping-particle" : "", "family" : "Janipalli", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumar", "given" : "M V K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinay", "given" : "D G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandeep", "given" : "M N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhaskar", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kulkarni", "given" : "S R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aruna", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Joglekar", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Priyadharshini", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maheshwari", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yajnik", "given" : "C S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chandak", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetic medicine : a journal of the British Diabetic Association", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "121-7", "title" : "Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of Type 2 diabetes and related traits in Indians.", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "80", "plainTextFormattedCitation" : "80", "previouslyFormattedCitation" : "80" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }80YYgeneral population in Pune and surrounding areasparents of children in the Pune Maternal Nutrition Study from urban and rural regions and Coronary Risk of Insulin Sensitivity in Indian Subjects studyBeen Nutr Metab 2012 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.numecd.2011.01.006", "ISSN" : "1590-3729", "PMID" : "21558052", "abstract" : "Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), \u03b2-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low \u2264 25 kg/m(2) and high > 25 kg/m(2)) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (\u03b2 = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (\u03b2 = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation.", "author" : [ { "dropping-particle" : "", "family" : "Been", "given" : "L F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hatfield", "given" : "J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shankar", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aston", "given" : "C E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "G S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "N K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "J J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nutrition, metabolism, and cardiovascular diseases : NMCD", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2012", "11" ] ] }, "page" : "944-51", "title" : "A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity.", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "246", "plainTextFormattedCitation" : "246", "previouslyFormattedCitation" : "246" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }246YYendogamous Khatri Sikh populationendogamous Khatri Sikh population with no family history of type 2 diabetes; 262 were non-diabetic spousesRaza Gene 2012 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.gene.2012.09.072", "ISSN" : "1879-0038", "PMID" : "23036708", "abstract" : "BACKGROUND: Type 2 diabetes mellitus is a multifactorial and polygenic disease, which is considered as a major life threatening problem all over the world. There has been a worldwide effort in the identification of susceptibility genes for type 2 diabetes mellitus and its complications. At present, adequate data is not available dealing with MTHFR (rs1801133) and PPAR\u03b32 (rs1801282) gene polymorphisms and its association with type 2 diabetes mellitus cases among north Indian populations. Thus, we conceived the need for further studies to investigate MTHFR and PPAR\u03b32 gene polymorphisms and their susceptibility to type 2 diabetes mellitus in north Indian population.\n\nMATERIALS AND METHODS: In this study, a total 175 subjects including 87 type 2 diabetes mellitus cases and 88 controls were enrolled. MTHFR and PPAR\u03b32 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).\n\nRESULTS: The MTHFR gene CC, CT, TT genotype frequencies obtained were 40%, 43%, and 17% in type 2 diabetes mellitus cases and 56%, 29%, and 15% in healthy controls respectively. The OR for CC was 0.54 (95%CI 0.29-0.98, P=0.041, \u03c7(2)=4.18, power=0.98), for CT 1.76 (95%CI 0.94-3.30, P=0.07, \u03c7(2)=3.2, power=0.96), and for TT 1.2 (95%CI 0.53-2.70, P=0.66, \u03c7(2)=0.198, power=0.76). The PPAR\u03b32 gene GG CG, CC genotype frequencies obtained were 28%, 41%, and 31% in cases and 40%, 39%, and 21% in healthy controls respectively. OR for GG was 0.58 (95%CI 0.30-1.09, P=0.08, \u03c7(2)=2.9, power=0.96), for CG 1.12 (95%CI 0.61-2.05, P=0.71, \u03c7(2)=0.137, power=0.778), and for CC 1.63 (95%CI 0.82-3.23, P=0.156, \u03c7(2)=2.01, power=0.92).\n\nCONCLUSION: It might be recommended that MTHFR CC genotype seems to be a good marker for the early identification of population at risk of type 2 diabetes mellitus. While we have detected significant difference in allelic frequencies of PPAR\u03b32 C (Proline) and G (Alanine), but at genotypic level significant difference was not detected in this case-control study. Further study with larger groups may be required to validate the study.", "author" : [ { "dropping-particle" : "", "family" : "Raza", "given" : "Syed Tasleem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbas", "given" : "Shania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahmed", "given" : "Faisal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fatima", "given" : "Jalees", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaidi", "given" : "Zeashan Haider", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahdi", "given" : "Farzana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Gene", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "12", "15" ] ] }, "page" : "375-9", "title" : "Association of MTHFR and PPAR\u03b32 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population.", "type" : "article-journal", "volume" : "511" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "85", "plainTextFormattedCitation" : "85", "previouslyFormattedCitation" : "85" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }85not reportednot reportedrecruited from a diabetic clinicrecruited from same diabetic clinic with no history of type 2 diabetesAnand Diabetes Care 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc12-2553", "ISSN" : "1935-5548", "PMID" : "23603917", "abstract" : "OBJECTIVE: To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.\n\nRESEARCH DESIGN AND METHODS: In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.\n\nRESULTS: Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).\n\nCONCLUSIONS: T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pare", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailey", "given" : "Swneke D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Changchun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Xiaohe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montpetit", "given" : "Alexandre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "Dipika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "Jackie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordell", "given" : "Heather J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keavney", "given" : "Bernard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaudet", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "Hertzel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engert", "given" : "James C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes care", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "9" ] ] }, "page" : "2836-42", "title" : "Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "62", "plainTextFormattedCitation" : "62", "previouslyFormattedCitation" : "62" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }62YYIndividuals at risk for dysglycemia recruited from 191 centres around the world via a variety of methodsSample population as casesAli PLoS One 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0058881", "ISSN" : "1932-6203", "PMID" : "23527042", "abstract" : "Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E-04) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value\u200a=\u200a2.05E-08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR\u200a=\u200a2.44, (95%CI\u200a=\u200a1.67-3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.", "author" : [ { "dropping-particle" : "", "family" : "Ali", "given" : "Shafat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chopra", "given" : "Rupali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manvati", "given" : "Siddharth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Yoginder Pal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaul", "given" : "Nabodita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Behura", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Ankit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sehajpal", "given" : "Prabodh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gupta", "given" : "Subash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhar", "given" : "Manoj K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chainy", "given" : "Gagan B N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhanwer", "given" : "Amarjit S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Swarkar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bamezai", "given" : "Rameshwar N K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "editor" : [ { "dropping-particle" : "", "family" : "Dewan", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "e58881", "publisher" : "Public Library of Science", "title" : "Replication of type 2 diabetes candidate genes variations in three geographically unrelated Indian population groups.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "247", "plainTextFormattedCitation" : "247", "previouslyFormattedCitation" : "247" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }247YY--Saxena Diabetes 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-1077", "ISSN" : "1939-327X", "PMID" : "23300278", "abstract" : "We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 individuals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P < 10\u207b\u00b3) in Punjabi Sikhs (n = 2,819; 801 case subjects). We further replicated 66 SNPs (P < 10\u207b\u2074) through genotyping in a Punjabi Sikh sample (n = 2,894; 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329; 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 \u00d7 10\u207b\u2078) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P < 10\u207b\u00b3) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P < 10\u207b\u2074) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P < 10\u207b\u2075 to < 10\u207b\u2077), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 individuals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.", "author" : [ { "dropping-particle" : "", "family" : "Saxena", "given" : "Richa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saleheen", "given" : "Danish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Been", "given" : "Latonya F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garavito", "given" : "Martha L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bjonnes", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Young", "given" : "Robin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Weang Kee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasheed", "given" : "Asif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frossard", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sim", "given" : "Xueling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanali", "given" : "Neelam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Radha", "given" : "Venkatesan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liju", "given" : "Samuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Simon D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ng", "given" : "Daniel Peng-Keat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "Tien-Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamauchi", "given" : "Toshimasa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hara", "given" : "Kazuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Yasushi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirose", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "Andrew P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basit", "given" : "Abdul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnett", "given" : "Anthony H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulanda", "given" : "Prasad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wander", "given" : "Gurpreet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Jai Rup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mehra", "given" : "Narinder K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ralhan", "given" : "Sarju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kamboh", "given" : "M Ilyas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulvihill", "given" : "John J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maegawa", "given" : "Hiroshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tobe", "given" : "Kazuyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maeda", "given" : "Shiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cho", "given" : "Yoon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tai", "given" : "E Shyong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "M Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chambers", "given" : "John C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kooner", "given" : "Jaspal S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kadowaki", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rader", "given" : "Daniel J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danesh", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanghera", "given" : "Dharambir K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "5" ] ] }, "page" : "1746-55", "title" : "Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "73", "plainTextFormattedCitation" : "73", "previouslyFormattedCitation" : "73" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }73YYLOLIPOP: recruited from lists of GPs in West London; PROMIS: out-patient departments; SINDI: general population; DGP: hospitals or Diabetes awareness camps; CURES: general population; SDS: endogamous Khatri Sikh population; RACE: recruited from six hospital centres in Pakistan; UKADS: general population; SLDS: general populationLOLIPOP: recruited from lists of GPs in West London; PROMIS: matched cases from visitors in out-patient; SINDI: general population; DGP: recruited from community screening camps; CURES: random sampling from general population; SDS: endogamous Khatri Sikh population with no family history of type 2 diabetes, 262 were non-diabetic spouses RACE: recruited from six hospital centres in Pakistan; UKADS: general population (same geographical area); SLDS: general populationTabassum Diabetes 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db12-0406", "ISSN" : "1939-327X", "PMID" : "23209189", "abstract" : "Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 \u00d7 10\u207b\u2079). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 \u00d7 10\u207b\u00b9\u00b2) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.", "author" : [ { "dropping-particle" : "", "family" : "Tabassum", "given" : "Rubina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chauhan", "given" : "Ganesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwivedi", "given" : "Om Prakash", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahajan", "given" : "Anubha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaiswal", "given" : "Alok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaur", "given" : "Ismeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandesh", "given" : "Khushdeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Tejbir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathai", "given" : "Benan John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pandey", "given" : "Yogesh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidambaram", "given" : "Manickam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharma", "given" : "Amitabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavali", "given" : "Sreenivas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sengupta", "given" : "Shantanu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramakrishnan", "given" : "Lakshmi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesh", "given" : "Pradeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aggarwal", "given" : "Sanjay K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghosh", "given" : "Saurabh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prabhakaran", "given" : "Dorairaj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Srinath", "given" : "Reddy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saxena", "given" : "Madhukar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Banerjee", "given" : "Monisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathur", "given" : "Sandeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bhansali", "given" : "Anil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shah", "given" : "Viral N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madhu", "given" : "Sri Venkata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marwaha", "given" : "Raman K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basu", "given" : "Analabha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scaria", "given" : "Vinod", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Venkatesan", "given" : "Radha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "Viswanathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tandon", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bharadwaj", "given" : "Dwaipayan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "977-86", "title" : "Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "72", "plainTextFormattedCitation" : "72", "previouslyFormattedCitation" : "72" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }72YYINDICO: consecutively recruited from the Endocrinology clinic of All India Institute of Medical Sciences; CURES: general populationINDICO: recruited from diabetes awareness camps; CURES: general populationUma Jyothi PLoS One 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0060212", "ISSN" : "1932-6203", "PMID" : "23577093", "abstract" : "We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established.", "author" : [ { "dropping-particle" : "", "family" : "Uma Jyothi", "given" : "Kommoju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jayaraj", "given" : "Maruda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subburaj", "given" : "Kadarkarai Samy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prasad", "given" : "Kotla Jaya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kumuda", "given" : "Irgam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakshmi", "given" : "Velaga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reddy", "given" : "Battini Mohan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "e60212", "title" : "Association of TCF7L2 gene polymorphisms with T2DM in the population of Hyderabad, India.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "82", "plainTextFormattedCitation" : "82", "previouslyFormattedCitation" : "82" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }82YYrecruited from J.P. Endocrine centercommunity diabetic campTariq Mol Vis 2013 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1090-0535", "PMID" : "23559865", "abstract" : "PURPOSE: The association of non-synonymous substitution polymorphism rs1801282 (c.34C>G, p.Pro12Ala) in exon 4 of the peroxisome proliferator activated receptor gamma gene with diabetic retinopathy (DR) has been reported inconsistently. Therefore, the purpose of the present study was to understand the population-specific role of the Pro12Ala polymorphism in DR susceptibility in Pakistani subjects.\n\nMETHODS: A total of 180 subjects with DR, 193 subjects with type 2 diabetes mellitus (T2DM) with no diabetic retinopathy, and 200 healthy normoglycemic non-retinopathic Pakistani individuals were genotyped for the rs1801282 (c.34C>G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism.\n\nRESULTS: We found the individuals with T2DM carrying 12Ala were at a reduced risk of developing DR (odds ratio [OR]=0.53; 95% confidence interval [CI]=0.33-0.87). Upon stratified analysis regarding disease severity, we observed this protective effect was confined to proliferative DR (OR=0.4; 95% CI=0.2-0.8) with non-significant effects on the susceptibility of non-proliferative DR (OR=0.67; 95% CI=0.37-1.19).\n\nCONCLUSIONS: We report a protective role of the 12Ala polymorphism against proliferative DR in individuals with T2DM in Pakistan.", "author" : [ { "dropping-particle" : "", "family" : "Tariq", "given" : "Khadija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malik", "given" : "Saira Bano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ali", "given" : "Syeda Hafiza Benish", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maqsood", "given" : "Sundas Ejaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Azam", "given" : "Aisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muslim", "given" : "Irfan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Muhammad Shakil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Azam", "given" : "Maleeha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waheed", "given" : "Nadia Khalida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qamar", "given" : "Raheel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular vision", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "710-7", "title" : "Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "248", "plainTextFormattedCitation" : "248", "previouslyFormattedCitation" : "248" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }248Ynot reported; 10% replicated with 100% concordancerecruited from hospitalsnot specifiedSupplementary Table 3. SEQ Supplementary_Table_3. \* ARABIC 1 Risk allele frequencies and HWE-P values for SNPs available in the EpiDREAM cohortWhite Caucasians (n=2,651)South Asians (n=2,651)GeneSNPProxy SNPRisk alleleRAFGenotype distributionHWEPProxy SNPRisk alleleGenotype distributionRAFHWEPGIPRrs10423928T0.80118/848/16850.403T51/666/19340.860.530SLC2A2rs11920090rs10513685G0.8650/639/19620.871rs10513688G33/570/20480.880.407MTNR1Brs10830963G0.69259/1109/12830.386G486/1263/9020.580.232SLC30A8rs13266634C0.72217/1073/13610.775C126/899/16250.780.909FADS1rs174550rs174535T0.67292/1189/11690.727T30/512/21090.891.000MTNR1Brs2166706rs10830962C0.43481/1309/8560.634G624/1261/7660.470.019PDX1rs2293941A0.23128/946/15770.376A83/661/19060.160.008FOXA2rs6048205A0.959/226/24150.177A2/146/24600.971.000TCF7L2rs7903146T0.32282/1141/12280.477T261/1128/12620.310.717GCKrs4607517rs6975024C0.1897/762/17890.168rs2908282T49/583/20190.130.341PCSK1rs13179048rs17085675A0.72213/1063/13750.701rs4869272T320/1150/11810.660.129Supplementary Table 3. SEQ Supplementary_Table_3. \* ARABIC 2 Effect of 11 SNPs included in the genotype score on fasting glucose from published GWA-studiesGeneSNPEffect size (in mmol/l)FADS1rs1745500.017FOXA2rs60482050.040GCKrs46075170.062GIPRrs104239280.090IPF1/PDX1rs22939410.019MTNR1Brs21667060.070MTNR1Brs108309630.067PCSK1rs131790480.022SLC2A2rs119200900.020SLC30A8rs13266634 0.027TCF7L2rs79031460.023Supplementary Table 3.3 Genotypic effects for SNPs stratified by glucose traits and ethnicityGeneSNPGlucose traitWhite Caucasians (n=2,651)South Asians (n=2,651)Proxy SNPβ-coefficientPProxy SNPβ-coefficientPGIPRrs10423928AUC glucose0.292.28x10-20.392.28x10-2SLC2A2rs11920090AUC glucosers105136850.085.71x10-1rs10513688-0.116.40x10-1MTNR1Brs10830963AUC glucose-0.047.30x10-1-0.251.06x10-1SLC30A8rs13266634AUC glucose0.084.80x10-1-0.058.11x10-1FADS1rs174550AUC glucosers174535-0.028.42x10-10.019.67x10-1MTNR1Brs2166706AUC glucosers10830962-0.084.21x10-1-0.105.30x10-1PDX1rs2293941AUC glucose-0.019.29x10-10.184.08x10-1FOXA2rs6048205AUC glucose0.437.64x10-2-0.344.77x10-1TCF7L2rs7903146AUC glucose0.384.43x10-4-0.028.88x10-1GCKrs4607517AUC glucosers69750240.152.52x10-1rs2908282-0.087.29x10-1PCSK1rs13179048AUC glucosers17085675<0.019.99x10-1rs4869272-0.316.20x10-2GIPRrs10423928Fasting glucose0.043.31x10-10.111.18x10-1SLC2A2rs11920090Fasting glucosers105136850.018.14x10-1rs10513688-0.074.06x10-1MTNR1Brs10830963Fasting glucose-0.065.86x10-2-0.071.93x10-1SLC30A8rs13266634Fasting glucose0.042.94x10-10.009.36x10-1FADS1rs174550Fasting glucosers174535-0.042.81x10-10.028.34x10-1MTNR1Brs2166706Fasting glucosers10830962-0.042.48x10-1-0.044.51x10-1PDX1rs2293941Fasting glucose0.033.87x10-10.036.88x10-1FOXA2rs6048205Fasting glucose0.145.61X10-2-0.114.82x10-1TCF7L2rs7903146Fasting glucose0.103.18x10-3-0.027.02x10-1GCKrs4607517Fasting glucosers69750240.083.72x10-2rs29082820.027.71x10-1PCSK1rs13179048Fasting glucosers170856750.033.33x10-1rs4869272-0.114.63x10-2Supplementary Figure 3. SEQ Supplementary_Figure_3. \* ARABIC 1 Histograms of AUC glucose (a) and fasting glucose (b)(a)(b) Supplementary Figure 3. SEQ Supplementary_Figure_3. \* ARABIC 2 First three principle components for (a) South Asians and (b) white Caucasians (a)(b)Supplementary Figure 3. SEQ Supplementary_Figure_3. \* ARABIC 3 Histograms of coefficients of inbreeding in (a) South Asians and (b) white Caucasians(a)(b)Supplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 1 Inclusion and exclusion criteria for the START and CHILD cohortsInclusion CriteriaExclusion CriteriaSTART cohortWomen between the ages of 18 and 40South Asian originPregnant with a single fetusExpected multiple birthsArtificial / Assisted conception of fetus>4 live birthsSurrogate mothersLiving in Canada <9 monthsFather of the baby is not South AsianFollowing chronic medication conditions: - Active cancers - HIV - Hepatitis B or C - VDRL Positive - Rheumatic Heart Disease - Seizure DisorderCHILD cohortPregnant women aged 18 years and older (19 in Vancouver)Residence in reasonable proximity to the delivery hospitalAble to read, write, and speak EnglishWilling to provide informed consentWilling to consent to cord blood collection for the studyPlanning to give birth at a designated recruitment centre participating hospitalInfants born at or after 35 weeksAble to provide name, address and telephone numbers of two alternate contact individualsChildren born with major congenital abnormalities or respiratory distress syndrome (RDS)Expectation of moving away from a recruitment area within 1 yearChildren of multiple birthsChildren resulting from in vitro fertilizationChildren who will not spend at least 80% of nights in the index homeChildren born before 35 weeks gestationSupplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 2 Allele frequencies and HWE-P values for SNPs available in the START and CHILD cohorts.GeneProxy SNPTraitAlleleSouth AsiansWhite CaucasiansAFHWE-PAFHWE-PADCY5rs2877716Birth weightA0.2490.7360.2700.860ZBTB38rs9846396Birth lengthA0.3210.1910.4460.035CCNL1rs17451107Birth weightG0.2700.5220.3730.051LCORLrs724577Birth weight / lengthA0.1960.2240.2571.000CDKAL1rs9368222Birth weightA0.2520.7360.2730.727GPR126rs155259Birth lengthA0.3421.0000.2820.002JAZF1rs849141Birth lengthA0.2900.0140.2590.856CALCRrs6968642Birth weightA0.3770.4990.4491.000HHEXrs10882099Birth weightG0.5630.3020.3870.057TCF7L2rs4132670Birth weightA0.3020.7630.3400.876ADRB1rs740746Birth weightG0.2680.4210.2970.402HMGA2rs10784502Birth weightG0.2761.0000.4710.402HMGA2rs8756Birth lengthC0.2720.8730.4730.676ADAMTSL3rs4842838Birth lengthC0.4080.8950.4710.482ANKRD13Brs565977Birth lengthA0.4380.1970.3090.033ACBD4rs4986172Birth lengthA0.3430.4020.3061.000GDF5rs6087704Birth lengthG0.5570.2480.4040.662Supplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 3 Genes (and SNPs) chosen for investigation in the primary analysis from a literature searchGeneSNPTraitLCORLrs724577birth lengthPTCH1rs473902birth lengthGPR126rs7763064birth lengthHMGA2rs1351394birth lengthDCST2rs905938birth lengthSF3B4rs11205277birth lengthPTPDC1rs1257763birth lengthHHIPrs7689420birth lengthADAMTSL3rs11259936birth lengthZBTB38rs724016birth lengthHMGA1rs2780226birth lengthIGF1Rrs2871865birth lengthGDF5rs143384birth lengthDTLrs10863936birth lengthJAZF1rs1708299birth lengthACBD4rs4986172birth lengthANKRD13Brs3110496birth lengthPMLrs5742915birth lengthCCNL1rs900400birth weightCENPMrs5758511birth weightADCY5rs9883204birth weightHMGA2rs1042725birth weightCDKAL1rs6931514birth weightCALCRrs7780752birth weightACTBL2rs4432842birth weightLCORLrs724577birth weightADRB1rs1801253birth weightSLC2A4rs5415birth weightTCF7L2rs7903146birth weightHHEX-IDErs1111875birth weightIGF-1-Birth weight / lengthIGF-2-Birth weight / lengthSupplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 4 Global methylation differences between START and CHILD cohortsComparison groupsN South AsiansN white CaucasiansEstimated heterogeneity varianceP heterogeneitySTART vs. CHILD2342500.00022<0.01A 1000 CpG sites across the genome were randomly selected and the average methylation level was meta-analysed to estimate global methylation. Heterogeneity estimates for the meta-analysis is presented above.Supplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 5 SNP associations for birth weight genes in South Asians and white Caucasian newbornsGeneLead SNPProxy SNPRisk alleleSouth AsianWhite Caucasiansβ-coefficientPPower*β-coefficientPPower*ADCY5rs9883204rs2877716C0.017 6.99 x10-10.05-0.042 3.91 x10-10.05CALCRrs7780752rs6968642C0.00039.93 x10-10.050.015 7.27 x10-10.05HHEXrs1111875rs10882099T-0.007 8.58 x10-10.05-0.008 8.55 x10-10.05TCF7L2rs7903146rs4132670G-0.047 2.66 x10-10.05-0.101 2.27 x10-20.05ADRB1rs1801253rs740746G0.004 9.37 x10-10.050.030 5.30 x10-10.05HMGA2rs1042725rs10784502T-0.074 7.66 x10-20.05-0.063 1.52 x10-10.05CCNL1rs900400rs17451107G-0.037 3.79 x10-10.05-0.040 3.26 x10-10.05LCORLrs724577rs724577C-0.089 7.52 x10-20.05-0.062 1.99 x10-10.05CDKAL1rs6931514rs9368222A-0.0893.98 x10-20.05-0.022 6.46 x10-10.05Genotype score-0.0212.05 x10-1-0.0421.36 x10-2* Calculated using a β-coefficient of 0.07 gram change in birth weight, congruent with estimates reported from GWA-studies, and allele frequency and sample size in our sampleSupplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 6 SNP associations for birth length genes in South Asian and white Caucasian newbornsGeneLead SNPProxy SNPRisk alleleSouth AsianWhite Caucasiansβ-coefficientPPower*β-coefficientPPower*ZBTB38rs724016rs9846396A0.05 8.42 x10-10.1010.03 9.24 x10-10.108GPR126rs7763064rs155259A0.39 1.35 x10-10.103-0.29 4.43 x10-10.097JAZF1rs1708299rs849141G0.10 6.82 x10-10.098-0.54 1.10 x10-10.095ADAMTSL3rs11259936rs4842838C0.18 4.95 x10-10.1070.273.40 x10-10.109ANKRD13Brs3110496rs565977A-0.20 4.49 x10-10.108-0.214.88 x10-10.100ACBD4rs4986172rs4986172A-0.15 5.59 x10-10.1030.273.98 x10-10.106HMGA2rs1351394rs8756A0.01 9.72 x10-10.097-0.40 1.93 x10-10.109LCORLrs724577rs724577C-0.156.55 x10-10.087-0.432.12 x10-10.095GDF5rs143384rs6087704G-0.155.24 x10-10.108-0.26 4.01 x10-10.106Genotype score-0.065.39 x10-1-0.113.23 x10-1* Calculated using a β-coefficient of 0.1 SD change in birth length, congruent with estimates reported from GWA-studies, and allele frequency and sample size in our sampleSupplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 7 Overview of key differences in blood collection protocols of the START and CHILD cohortsSTARTCHILDTime of cord-blood collectionBefore placentaAfter placenta, except TorontoProcessing timeLess than 2 hours Less than 24 hours – mean=19.8 hours; range=0.33-321.70 hoursSupplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 8 Variation in leukocyte and erythrocyte cell type composition between South Asians and white Caucasians from the CHILD cohortCell typeSouth Asian MeanWhite Caucasian MeanP-valueLymphocytes4.634.836.24x10-1Monocytes1.211.481.72x10-1Neutrophils7.148.082.15x10-1Nucleated Red Blood Cells1.111.267.42x10-1Eosinophils0.330.466.36x10-2Basophils0.100.109.22x10-1Supplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 9 Association between CpG sites showing ethnic heterogeneity for birth weight in South Asians from the CHILD cohort (n=18) GeneCpG siteβ-coefficient*PTCF7L2cg09022607-0.00453.33 x10-1CALCRcg23061150-0.00443.15 x10-1HMGA2cg24892571-0.01195.23 x10-2HMGA2cg24776736-0.00294.02 x10-1TCF7L2cg11748187-0.00671.32 x10-1IGF1cg013054210.01049.86 x10-1CDKAL1cg065122630.00029.63 x10-1* β-coefficient adjusted for gestational age and sexSupplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 10 Effect of processing time on methylation level in the CHILD cohortGeneCpG site% methylationProcessing time < 2 hoursN=14% methylationProcessing time > 2 hoursN=227P-value*TCF7L2cg0902260728.529.21.28x10-1CALCRcg2306115082.081.95.46x10-1HMGA2cg2489257185.985.88.77x10-1HMGA2cg2477673659.359.24.61x10-1TCF7L2cg1174818736.037.54.86x10-5IGF1cg0130542118.619.87.73x10-1CDKAL1cg0651226326.427.25.92x10-1* P-value for the relationship between processing time and methylation at the designated CpG siteSupplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 11 Effect of processing time on methylation level in the CHILD cohortGeneCpG siteβ-coefficient N=14P-valueβ-coefficient N=227P-valueTCF7L2cg090226070.0038.93x10-1-0.0351.31x10-4CALCRcg23061150-0.0133.74x10-1-0.0273.57x10-3HMGA2cg24892571-0.0165.40x10-1-0.0227.13x10-2HMGA2cg24776736-0.0104.77x10-1-0.0227.82x10-5TCF7L2cg117481870.0172.59x10-1-0.0171.34x10-3IGF1cg013054210.0067.76x10-1-0.0241.33x10-4CDKAL1cg06512263-0.0038.80x10-1-0.0162.65x10-3Supplementary Table 4. SEQ Supplementary_Table_4. \* ARABIC 12 Percent of variance explained by clinical variables and CpG sites on birth weight in white CaucasiansVariables in the modelVariance explained (%)Gestational age24.1 + Sex24.9 + Gestational diabetes25.0 + Mother’s pre-pregnancy BMI32.5 + Smoking exposure34.1 + Mother’s hypertension during pregnancy34.5 + cg0902260735.0 + cg2477673635.3 + cg2306115036.5 + cg0130542136.8 + cg0651226336.9 + cg1174818737.4 + cg2489257137.7Supplementary Figure 4. SEQ Supplementary_Figure_4. \* ARABIC 1 Histograms of birth weight in South Asians (a) and white Caucasians (b); birth length in South Asians (c) and fasting glucose (d)(a)(b)(c) (d) ................
................

In order to avoid copyright disputes, this page is only a partial summary.

To fulfill the demand for quickly locating and searching documents.

It is intelligent file search solution for home and business.

Literature Lottery

Introduction - McMaster University

To fulfill the demand for quickly locating and searching documents.

Related download

Related searches