Literature Review - McMaster University



The Genetics of Obesity and Eating Disorders Genetics of nutirent consumption and an evolutionary Perspective of eating disordersBy Alexandra Jean Mayhew, B.A.ScA Thesis submitted to the School of Graduate studies in partial fulfilment of the requirements for the degree Master of Science McMaster University ? Copyright by Alexandra Jean Mayhew, July 2014McMaster University MASTER OF SCIENCE (2014) Hamilton, Ontario (Health Research Methodology)Title: Genetics of Nutrient Consumption and an Evolutionary Perspective of Eating Disorders Author: Alexandra Jean Mayhew, B.A.Sc (University of Guelph)Supervisor: Dr. David Meyre Number of PageS: 146Abstractgenetics of nutrient consumption and an evolutionary perspective of eating disordersAlexandra Jean MayhewAdvisor: Dr. David MeyreMcMaster University, 2014Committee Member: Dr. Sonia AnandCommittee Member: Dr. Andrew MenteObesity prevalence continues to increase worldwide, yet few safe and effective treatment options are available suggesting there needs to be a greater emphasis on preventing rather than treating obesity. This research investigated the association of obesity predisposing SNPs and a gene score with nutrient consumption patterns including total energy intake and macronutrient distribution in a European ancestry population as well as discussing an evolutionary perspective on eating disorders using current epidemiological evidence to identify genes which may be involved. The association of two of the 14 obesity predisposing SNPs and the gene score with BMI was confirmed in the EpiDREAM population. Novel associations between two SNPs located in or near BDNF (rs6265 and rs1401635) were found with total fat, MUFA, and PUFA intake. Rs1401635 was also associated with total energy and trans fat intake. Novel associations of rs6235 (PCSK1) and the gene score were found with total energy intake. The novel associations found indicate that food related behaviours are one of the mechanisms of action through which obesity predisposing SNPs cause obesity and therefore warrant further investigation. The lack of association among all genes and the modest association of the gene score show that mechanisms other than food consumption are important. The investigation of the evolutionary history of eating disorders revealed that the adapted to flee famine hypothesis is a plausible theory explaining anorexia nervosa while the thrifty genotype hypothesis provides a possible explanation for bulimia nervosa and binge eating disorder. These evolutionary theories can be applied to identify new candidate genes as well as phenotypic traits to investigate to better understand the genetic architecture of eating disorders. Understanding genes associated with disordered eating patterns may highlight future areas for obesity prevention. Key words: obesity, polygenic obesity, BMI, SNP, gene score, energy intake, macronutrient, eating disorders, anorexia nervosa, bulimia nervosa, binge eating disorder, thrifty genotype hypothesis, adapted to flee famine hypothesis. AcknowledgementsI would like to begin by thanking my advisor, Dr. David Meyre for his continued support and guidance throughout the duration of my Masters. His passion for understanding the genetics of obesity, dedication to his students, and willingness to teach made this thesis a reality. My research also benefited greatly from my committee members Drs. Sonia Anand and Andrew Mente who provided exceptional suggestions for improving this thesis. A special thank you goes out to my peers and additional mentors, Russell de Souza, Aihua Li, and Sébastien Robiou-du-Pont, who played important roles in developing my skills and understanding. I thank my parents, John and Rose Mayhew for encouraging me from day one to pursue a career in academia and providing support in countless ways over the many years of school. I thank my friends Lindsay Morris, Claudia Chan, Jill Patrick, Victor and Tori Da Silva Sa, Allison Davis, Chris Bonanno, Florence Wilson, Ray Flores, Matt and Julia Stoop, and Nicole Seymour for boosting my spirits when overwhelmed and for their continued friendship. Lastly, I thank my partner Alexander Jensen for providing the support necessary to push forward during the most challenging times through his endless patience and unwavering belief in my abilities. Table of ContentsTitle Page…………………………………………………………………………………..iDescriptive note…………………………………………………………………………...iiAbstract…………………………………………………………………………………...iiiAcknowledgements……………………………………………………………………….ivTable of contents…………………………………………………………………………..vList of figures and tables………………………………………………………………..viiiList of abbreviations……………………………………………………………………...xiDeclaration of academic achievement…………………………………………………...xii TOC \o "1-3" \h \z \u 1.0Introduction PAGEREF _Toc396123142 \h 12.0Literature Review PAGEREF _Toc396123143 \h 42.1 Heritability of obesity PAGEREF _Toc396123144 \h 42.2 Heritability of eating characteristics PAGEREF _Toc396123145 \h 72.2.1 Energy consumption and macronutrient distribution PAGEREF _Toc396123146 \h 72.2.2 Food consumption patterns PAGEREF _Toc396123147 \h 92.2.3 Food consumption behaviours PAGEREF _Toc396123148 \h 102.2.4 Conclusions PAGEREF _Toc396123149 \h 122.3 Current state of knowledge of the genetics of obesity PAGEREF _Toc396123150 \h 132.3.1 Monogenic obesity PAGEREF _Toc396123151 \h 132.3.2 Polygenic forms of obesity PAGEREF _Toc396123152 \h 162.4 Current state of knowledge of the genetics of eating behaviour PAGEREF _Toc396123153 \h 202.5 Background of eating disorders PAGEREF _Toc396123154 \h 232.5.1 Diagnostic criteria PAGEREF _Toc396123155 \h 232.5.2 Symptoms, comorbidities, and mortality of eating disorders PAGEREF _Toc396123156 \h 242.5.3 Treatment PAGEREF _Toc396123157 \h 252.5.4 Risk factors for eating disorders PAGEREF _Toc396123158 \h 272.6 Heritability of eating disorders PAGEREF _Toc396123159 \h 392.7 Genetics of eating disorders PAGEREF _Toc396123160 \h 402.7.1 Serotonin PAGEREF _Toc396123161 \h 412.7.2 Catecholamine pathway PAGEREF _Toc396123162 \h 442.7.3 Norephinephrine PAGEREF _Toc396123163 \h 472.7.4 Neuropeptides and Feed Regulations PAGEREF _Toc396123164 \h 482.7.5 Summary PAGEREF _Toc396123165 \h 553.0 Justification and Objectives PAGEREF _Toc396123166 \h 564.0 The Association of Obesity SNPs with Food Consumption Patterns PAGEREF _Toc396123167 \h 594.1 Introduction PAGEREF _Toc396123168 \h 594.2 Methods PAGEREF _Toc396123169 \h 624.2.1 Participants PAGEREF _Toc396123170 \h 624.2.2 Phenotyping PAGEREF _Toc396123171 \h 644.2.3 Genotyping PAGEREF _Toc396123172 \h 644.2.4 Statistical methods PAGEREF _Toc396123173 \h 654.3 Results PAGEREF _Toc396123174 \h 674.3.1 Association of obesity predisposing SNPs and genotype score with BMI PAGEREF _Toc396123175 \h 704.3.2 Association of obesity predisposing SNPs and genotype score with dietary intake parameters PAGEREF _Toc396123176 \h 734.4 Discussion PAGEREF _Toc396123177 \h 734.5 Conclusions PAGEREF _Toc396123178 \h 785.0 An Evolutionary Perspective on Eating Disorders PAGEREF _Toc396123179 \h 795.1 Introduction PAGEREF _Toc396123180 \h 795.2 Suppression of reproduction and sexual competition PAGEREF _Toc396123181 \h 795.3 Adapted to flee famine hypothesis and rogue hibernation PAGEREF _Toc396123182 \h 815.4 Thrifty gene hypothesis PAGEREF _Toc396123183 \h 845.5 Summary of evolutionary theories PAGEREF _Toc396123184 \h 895.6 Coexistence of Anorexia Nervosa and Bulimia Nervosa in binge/purge subtype Anorexia Nervosa PAGEREF _Toc396123185 \h 925.6.1 Binge eating as protection against Anorexia Nervosa PAGEREF _Toc396123186 \h 925.6.2 Accumulation of independent genes leading to binge eating and Anorexia Nervosa PAGEREF _Toc396123187 \h 935.6.3 Mutations/structural gene variants with opposite effects in the same gene lead to AN or BN PAGEREF _Toc396123188 \h 945.6.4 Mutations in nearby genes result in partial linkage disequilibrium of Anorexia Nervosa and binge eating traits PAGEREF _Toc396123189 \h 955.6.5 Summary of the role of genetics in the coexistence of Anorexia Nervosa and Bulimia Nervosa in binge/purge subtype Anorexia Nervosa PAGEREF _Toc396123190 \h 965.7 Conclusions PAGEREF _Toc396123191 \h 976.0 Ethical Considerations PAGEREF _Toc396123192 \h 1007.0 Conclusions and Future Work PAGEREF _Toc396123193 \h 1038.0 References PAGEREF _Toc396123194 \h 109List of Figures and TablesFiguresFigure 1. The role of monogenic obesity genes in the melanocortin pathway………….15Figure 2. EpiDREAM participant flow chart……………………………………………63Figure 3. Statistical power for detecting associations between individual SNPs and BMI according to allele frequency and beta-coefficients with a sample size of 1,850 participants……………………………………………………………………………….67Figure 4. Framework for the risk of developing an eating disorder based on genotypic category and presence or absence of pressure to be thin………………………………...99TablesTable 1. Gene symbols and proteins coded……………………………………………...14Table 2. Genotypic information for obesity predisposing SNPs………………………...65Table 3. EpiDREAM Participant Characteristics………………………………………..68Table 4. Pearson correlations for unadjusted nutrient intakes....………………………...69Table 5. Association of energy and energy adjusted nutrients with BMI……………….69Table 6. The association of obesity predisposing SNPs with BMI and energy adjusted nutrients…………………………………………………………………………..71List of Abbreviations and Symbols5-HIAA – 5-hydroxyindoleacetic acid 5-HT – Serotonin 5-HT2A – 5-hydroxytryptamine receptor 2A5-HTTLPR – Serotonin-transporter-linked polymorphic region AFFH – Adapted to flee famine hypothesis AGRP – Agouti related peptideAN – Anorexia NervosaAN(BP) – Anorexia Nervosa binge/purge subtype AN(R) – Anorexia Nervosa restrictive subtype BDNF – Brain-derived neurotrophic factorBED – Binge eating disorder BMI – Body mass index (kg/m2)BN – Bulimia nervosaCBT – Cognitive behaviour therapy COMT – catecholamine-O-methyltransferase CSF – Cerebrospinal fluidCVD – Cardiovascular disease D2 – Dopamine receptor 2D3 – Dopamine receptor 3D4 – Dopamine receptor 4DAT1 – Dopamine transporter 1DNA – Deoxyribonucleic acidDRD2 – Dopamine receptor 2DDRD3 – Dopamine receptor 3DDRD4 – Dopamine receptor 4DDSM – Diagnostic and Statistical Manual of Mental Disorders DZ – Dizygotic twins FFQ – Food frequency questionnaire FTO – Fat mass and obesity associated geneGWAS – Genome wide association study HEW – Hardy-Weinberg equilibrium HOXB5 – homebox protein HVA – Homovanillic acid IBC – ITMAT Broad CareKCTD14 – Potassium channel tetramerization domain containing 14LEP – Leptin LEPR – Leptin receptor LOD – Logarithm of odds MAOA – Monoamine oxidase AMC3R – Melanocortin 3 receptor MC4R – Melanocortin 4 receptorMISTRA – Minnesota Study of Twins Reared ApartMRAP2 – Melanocortin 2 receptor accessory protein 2 MUFA – Monounsaturated fatty acidMZ – Monozygotic twinsNEGR1 – Neuronal growth regulator 1 NET – Norepinephrine transporter NHLBI – National Heart, Lung, and Blood Institute NIMH – National Institute of Mental Health NMDAr – Glutamate receptor NPL – Nonparametric linkage NPY – Neuropeptide YNSAL – National Survey of American Life NTRK2 – Neurotrophic tyrosine kinase receptor type 2 gene OGTT – Oral glucose tolerance testOLFM4 – OlfactomedinOPRD1 – Opioid delta receptor PCSK1 – Prohormone convertase 1PET – Positron emission tomography POMC - ProopiomelanocortinPUFA – Polyunsaturated fatty acidPVN – Paraventricular nucleus PYY – Peptide YYRCT – Randomized controlled trial RNA – Ribonucleic acidSH2B1 – SH2B adaptor protein 1SHARE – Study of Health Assessment and Risk Evaluation SIM1 – Single-minded homolog 1SNPs – Single nucleotide polymorphisms SPSS – Statistical Package for the Social Sciences TPH – Tryptophan hydroxylase Declaration of Academic AchievementMy supervisor Dr. David Meyre and myself developed the plans of analysis for the association of obesity predisposing SNPs with dietary consumption patterns with feedback from my committee members, Dr. Sonia Anand and Dr. Andrew Mente. The data used had previously been collected for the EpiDREAM study and the principle investigator, Dr. Hertzel Gerstein provided comments on the proposal. I performed the data cleaning and all statistical analysis for the project. Dr. Meyre and I conceptualized the paper on the evolutionary history of eating disorders together with all data collection and writing being performed by myself. Introduction Obesity is caused by a positive energy balance in which more calories are consumed than expended per day, leading to excessive fat accumulation in adipose tissue. Body mass index (BMI) is typically used to determine obesity at a population level. Using predetermined BMI categories, individuals under 18.5kg/m2 are underweight, 18.5 to 24.9 kg/m2 are normal weight, 25.0 to 29.9 kg/m2 are overweight and anyone over 30 kg/m2 is obese ADDIN 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" : [ [ "0" ] ] }, "title" : "Please see the Table of Contents for access to the PDF files.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(World Health Organization)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(World Health Organization). The studies used to determine the current cut off points for weight categories were conducted in European populations. Recent evidence from a multiethnic study showed that the cut-off point for obesity should be approximately 6kg/m2 lower in non-European populations to more accurately reflect the metabolic risk associated with weight such as blood pressure, glucose metabolism, and lipid metabolism ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/CIRCULATIONAHA.106.635011", "ISSN" : "1524-4539", "PMID" : "17420343", "abstract" : "BACKGROUND: Body mass index (BMI) is widely used to assess risk for cardiovascular disease and type 2 diabetes. Cut points for the classification of obesity (BMI >30 kg/m2) have been developed and validated among people of European descent. It is unknown whether these cut points are appropriate for non-European populations. We assessed the metabolic risk associated with BMI among South Asians, Chinese, Aboriginals, and Europeans. METHODS AND RESULTS: We randomly sampled 1078 subjects from 4 ethnic groups (289 South Asians, 281 Chinese, 207 Aboriginals, and 301 Europeans) from 4 regions in Canada. Principal components factor analysis was used to derive underlying latent or \"hidden\" factors associated with 14 clinical and biochemical cardiometabolic markers. Ethnic-specific BMI cut points were derived for 3 cardiometabolic factors. Three primary latent factors emerged that accounted for 56% of the variation in markers of glucose metabolism, lipid metabolism, and blood pressure. For a given BMI, elevated levels of glucose- and lipid-related factors were more likely to be present in South Asians, Chinese, and Aboriginals compared with Europeans, and elevated levels of the blood pressure-related factor were more likely to be present among Chinese compared with Europeans. The cut point to define obesity, as defined by distribution of glucose and lipid factors, is lower by approximately 6 kg/m2 among non-European groups compared with Europeans. CONCLUSIONS: Revisions may be warranted for BMI cut points to define obesity among South Asians, Chinese, and Aboriginals. Using these revised cut points would greatly increase the estimated burden of obesity-related metabolic disorders among non-European populations.", "author" : [ { "dropping-particle" : "", "family" : "Razak", "given" : "Fahad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shannon", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vuksan", "given" : "Vladimir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "Bonnie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Ruby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Koon K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McQueen", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007", "4", "24" ] ] }, "page" : "2111-2118", "title" : "Defining obesity cut points in a multiethnic population", "type" : "article-journal", "volume" : "115" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Razak et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Razak et al. 2007), supporting the need for the development and use of ethnic specific BMI categories. Additionally, the prevalence of obesity has been increasing globally. In 2008, it was estimated that 1.46 billion adults worldwide were overweight or obese with average BMI increasing by 0.4 to 0.5kg/m2 per decade from the 1980s ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(10)62037-5", "ISSN" : "1474-547X", "PMID" : "21295846", "abstract" : "Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI.", "author" : [ { "dropping-particle" : "", "family" : "Finucane", "given" : "Mariel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Gretchen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowan", "given" : "Melanie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danaei", "given" : "Goodarz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "John K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paciorek", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Gitanjali M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutierrez", "given" : "Hialy R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bahalim", "given" : "Adil N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farzadfar", "given" : "Farshad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Leanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ezzati", "given" : "Majid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9765", "issued" : { "date-parts" : [ [ "2011", "2", "12" ] ] }, "page" : "557-567", "publisher" : "Elsevier Ltd", "title" : "National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9\u00b71 million participants.", "type" : "article-journal", "volume" : "377" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Finucane et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Finucane et al. 2011). The greatest burden of disease is in Western countries. The United States has the highest percentage of obese adults ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(10)62037-5", "ISSN" : "1474-547X", "PMID" : "21295846", "abstract" : "Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI.", "author" : [ { "dropping-particle" : "", "family" : "Finucane", "given" : "Mariel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Gretchen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowan", "given" : "Melanie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danaei", "given" : "Goodarz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "John K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paciorek", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Gitanjali M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutierrez", "given" : "Hialy R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bahalim", "given" : "Adil N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farzadfar", "given" : "Farshad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Leanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ezzati", "given" : "Majid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9765", "issued" : { "date-parts" : [ [ "2011", "2", "12" ] ] }, "page" : "557-567", "publisher" : "Elsevier Ltd", "title" : "National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9\u00b71 million participants.", "type" : "article-journal", "volume" : "377" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Finucane et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Finucane et al. 2011). However, developing countries are experiencing the greatest increases in incidence of obesity and in the future will be the greatest contributors to the obesity epidemic ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(10)62037-5", "ISSN" : "1474-547X", "PMID" : "21295846", "abstract" : "Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI.", "author" : [ { "dropping-particle" : "", "family" : "Finucane", "given" : "Mariel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Gretchen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowan", "given" : "Melanie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danaei", "given" : "Goodarz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "John K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paciorek", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Gitanjali M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutierrez", "given" : "Hialy R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bahalim", "given" : "Adil N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farzadfar", "given" : "Farshad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Leanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ezzati", "given" : "Majid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9765", "issued" : { "date-parts" : [ [ "2011", "2", "12" ] ] }, "page" : "557-567", "publisher" : "Elsevier Ltd", "title" : "National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9\u00b71 million participants.", "type" : "article-journal", "volume" : "377" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Finucane et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Finucane et al. 2011). Obesity is associated with many health complications including type 2 diabetes, cardiovascular disease (CVD), fatty liver disease, cancer, obstructive sleep apnea, breathing difficulties, and musculoskeletal disability and pain ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pop.2009.01.009", "ISSN" : "1558-299X", "PMID" : "19501243", "abstract" : "Obesity, especially visceral adiposity, is associated with morbidity and mortality through endocrine and mechanical processes. Clinical manifestations due to effects of obesity on the cardiovascular, respiratory, gastrointestinal, musculoskeletal, immune, and integumentary systems have been described. Further studies are needed to understand the pathologic processes underlying these clinical manifestations to improve disease prevention.", "author" : [ { "dropping-particle" : "", "family" : "Schelbert", "given" : "Kavitha Bhat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Prim Care Clin Office Pract", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "6" ] ] }, "page" : "271-285", "publisher" : "Elsevier Ltd", "title" : "Comorbidities of obesity", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Schelbert 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Schelbert 2009). These complications contribute to severe forms of obesity decreasing life expectancy by 5 to 20 years ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fontaine", "given" : "Kevin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Redden", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Chenxi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westfall", "given" : "Andrew O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Med Assoc", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "187-193", "title" : "Years of life lost due to obesity", "type" : "article-journal", "volume" : "289" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fontaine et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fontaine et al. 2003). In addition to affecting health, obesity is also an economic burden. In the United States, the annual healthcare cost of obesity is estimated to be $56 billion with a positive association between BMI and per capita expenditure. Though difficult to measure, this number is much higher when considering the indirect costs of obesity, such as absenteeism, disability, and premature death ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.beem.2013.01.002", "ISSN" : "1878-1594", "PMID" : "23731873", "abstract" : "Obesity has substantially increased in recent decades and is now one of the major global health problems. The large obesity-related health burden negatively impacts many relevant health outcomes (e.g. quality of life, disability, mortality) and leads to increased healthcare utilization. This excess service use is the main driver behind high healthcare costs of obese individuals. Findings indicate that costs rise curvilinearly with increasing body mass index, especially among the obese. As more individuals of a country's population become obese, a larger share of total annual national healthcare expenditure is spent on obesity and obesity-related health problems. In addition to escalating healthcare costs, obesity goes along with indirect costs through decreases in workforce productivity. The empirical evidence has shown beyond doubt that obesity negatively impacts individuals, healthcare systems, employers, and the economy as a whole. This article provides a brief overview of selected economic consequences associated with excess-weight.", "author" : [ { "dropping-particle" : "", "family" : "Lehnert", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonntag", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konnopka", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riedel-Heller", "given" : "Steffi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6nig", "given" : "Hans-Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Best practice & research. Clinical endocrinology & metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "4" ] ] }, "page" : "105-115", "title" : "Economic costs of overweight and obesity", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Lehnert et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Lehnert et al. 2013). The treatments available for obese patients vary based on the degree of obesity and associated co-morbidities as well as the potential side effects of the therapeutic options. Interventions range from lifestyle modifications involving food restriction and increased energy expenditure through physical activity for those with mild obesity, to pharmacotherapy options for moderate obesity, and surgical interventions for those with the most extreme forms of obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2012-3115", "ISSN" : "1945-7197", "PMID" : "23443815", "abstract" : "Obesity is a disease that is defined as the accumulation of excessive amounts of body fat and is associated with increased risk of serious illness, disability, and death. In clinical practice, obesity is best assessed by calculating body mass index and measuring waist circumference. Treatment options are determined based on the body mass index, waist circumference, and adverse health consequences the patient is experiencing or is at an increased risk for facing in the future. Today, overweight and obesity impacts the majority of patients we treat in our clinical practices. Although endocrinologists are uniquely positioned to treat one of the major consequences of our current obesity epidemic, type 2 diabetes, we also need to be positioned and prepared to effectively treat one of its major causes-obesity. Type 2 diabetes and obesity are very much intertwined. Treatment of each disease affects the other. For these reasons, endocrinologists need to be experts in the treatment of obesity as well as diabetes. They should keep up with advances in obesity treatment including lifestyle, pharmaceutical, and surgical strategies. These strategies offer opportunities for improving the overall treatment for our obese patients today and will continue to improve and expand over the next decade.", "author" : [ { "dropping-particle" : "", "family" : "Wyatt", "given" : "Holly R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "4" ] ] }, "page" : "1299-306", "title" : "Update on treatment strategies for obesity.", "type" : "article-journal", "volume" : "98" }, "uris" : [ "", "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1467-789X.2011.00981.x", "ISSN" : "1467-789X", "PMID" : "22288431", "abstract" : "The study aims to compare anti-obesity interventions in a single evidence synthesis framework. Electronic databases were searched for randomized controlled trials of orlistat, rimonabant or sibutramine reporting weight or body mass index (BMI) change from baseline at 3, 6 or 12 months. A mixed treatment comparison was used to combine direct and indirect trial evidence. Ninety-four studies involving 24,808 individuals were included; 83 trials included data on weight change and 41 on BMI change. All results are in comparison with placebo. The active drugs were all effective at reducing weight and BMI. At 3 months, orlistat reduced weight by -2.65 kg (95% credibility interval -4.00 kg, -1.31 kg). For sibutramine, 15 mg gave a greater reduction than 10 mg at 12 months, -6.35 kg versus -5.42 kg, respectively. Rimonabant reduced weight by -11.23 kg at 3 months and -4.55 kg at 12 months. Lifestyle advice alone also reduced weight at 6 and 12 months, but was less effective than the pharmacological interventions. In conclusion, modest weight reductions were seen for all pharmacological interventions. Those interventions which have now been withdrawn from use (sibutramine and rimonabant) seem to be the most effective, implying that there may be a place in clinical practice for similar drugs if side effects could be avoided.", "author" : [ { "dropping-particle" : "", "family" : "Gray", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dunkley", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warren", "given" : "F C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ara", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abrams", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khunti", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutton", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity reviews : an official journal of the International Association for the Study of Obesity", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "6" ] ] }, "page" : "483-98", "title" : "A systematic review and mixed treatment comparison of pharmacological interventions for the treatment of obesity.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "", "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gray et al. 2012; Wyatt 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gray et al. 2012; Wyatt 2013). Despite the availability of diverse treatment options the effect of lifestyle interventions is modest and the more effective pharmacotherapy and surgical options are associated with serious complications. The lack of adequate treatments indicates that prevention may be the best strategy for curbing the obesity epidemic ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(11)60815-5", "ISSN" : "1474-547X", "PMID" : "21872752", "abstract" : "The global obesity epidemic has been escalating for four decades, yet sustained prevention efforts have barely begun. An emerging science that uses quantitative models has provided key insights into the dynamics of this epidemic, and enabled researchers to combine evidence and to calculate the effect of behaviours, interventions, and policies at several levels--from individual to population. Forecasts suggest that high rates of obesity will affect future population health and economics. Energy gap models have quantified the association of changes in energy intake and expenditure with weight change, and have documented the effect of higher intake on obesity prevalence. Empirical evidence that shows interventions are effective is limited but expanding. We identify several cost-effective policies that governments should prioritise for implementation. Systems science provides a framework for organising the complexity of forces driving the obesity epidemic and has important implications for policy makers. Many parties (such as governments, international organisations, the private sector, and civil society) need to contribute complementary actions in a coordinated approach. Priority actions include policies to improve the food and built environments, cross-cutting actions (such as leadership, healthy public policies, and monitoring), and much greater funding for prevention programmes. Increased investment in population obesity monitoring would improve the accuracy of forecasts and evaluations. The integration of actions within existing systems into both health and non-health sectors (trade, agriculture, transport, urban planning, and development) can greatly increase the influence and sustainability of policies. We call for a sustained worldwide effort to monitor, prevent, and control obesity.", "author" : [ { "dropping-particle" : "", "family" : "Gortmaker", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swinburn", "given" : "Boyd A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carter", "given" : "Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mabry", "given" : "Patricia L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finegood", "given" : "Diane T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Terry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marsh", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moodie", "given" : "Marjory L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9793", "issued" : { "date-parts" : [ [ "2011", "8", "27" ] ] }, "page" : "838-847", "publisher" : "Elsevier Ltd", "title" : "Changing the future of obesity: science, policy, and action.", "type" : "article-journal", "volume" : "378" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gortmaker et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gortmaker et al. 2011).One of the barriers to obesity prevention is the abundance of contributing causes of the disease. The availability of low cost, calorically dense foods and less physical activity demands are often cited as the two biggest contributors to the rising prevalence of obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/10408390903372599", "ISSN" : "1549-7852", "PMID" : "19960394", "abstract" : "The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic.", "author" : [ { "dropping-particle" : "", "family" : "McAllister", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dhurandhar", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keith", "given" : "Scott W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aronne", "given" : "Louis J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barger", "given" : "Jamie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baskin", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benca", "given" : "Ruth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biggio", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boggiano", "given" : "Mary M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eisenmann", "given" : "Joe C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elobeid", "given" : "Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontaine", "given" : "Kevin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluckman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanlon", "given" : "Erin C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katzmarzyk", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietrobelli", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Redden", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruden", "given" : "Douglas M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Chenxi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterland", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Suzanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Reviews in Food Science and Nutrition", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2009", "11" ] ] }, "page" : "868-913", "title" : "Ten putative contributors to the obesity epidemic", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(McAllister et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(McAllister et al. 2009), particularly in developing countries which are increasingly influenced by Western culture through globalization ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Malik", "given" : "Vasanti S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willett", "given" : "Walter C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Rev Endocrinol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "13-27", "title" : "Global obesity: trends, risk factors and policy implications", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Malik et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Malik et al. 2013). While energy balance is the most cited cause of obesity, other risk factors such as infections, epigenetic effects, maternal age, assortative mating, reproductive fitness, sleep debt, endocrine disruptors, pharmaceutical side effects, ambient temperature, and intrauterine and intergenerational effects have at minimum epidemiological evidence supporting their association with obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/10408390903372599", "ISSN" : "1549-7852", "PMID" : "19960394", "abstract" : "The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic.", "author" : [ { "dropping-particle" : "", "family" : "McAllister", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dhurandhar", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keith", "given" : "Scott W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aronne", "given" : "Louis J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barger", "given" : "Jamie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baskin", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benca", "given" : "Ruth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biggio", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boggiano", "given" : "Mary M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eisenmann", "given" : "Joe C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elobeid", "given" : "Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontaine", "given" : "Kevin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluckman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanlon", "given" : "Erin C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katzmarzyk", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietrobelli", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Redden", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruden", "given" : "Douglas M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Chenxi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterland", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Suzanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Reviews in Food Science and Nutrition", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2009", "11" ] ] }, "page" : "868-913", "title" : "Ten putative contributors to the obesity epidemic", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(McAllister et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(McAllister et al. 2009). Obesity risk is also partially attributable to genetic factors. Family and twin studies have established that 50 to 80% of the inter-individual variation in predisposition to obesity is because of genetic factors ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677921", "ISSN" : "1875-5488", "PMID" : "22043164", "abstract" : "Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of \"deep phenotyping\" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "154-168", "title" : "Molecular basis of obesity: current status and future prospects.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011b). In an effort to determine how to better prevent obesity, genome wide association studies (GWAS) and candidate gene studies have identified close to 70 loci associated with obesity-related traits. Despite the identification of obesity predisposing single nucleotide polymorphisms (SNPs), the underlying mechanisms are poorly understood. Food behaviors such as energy consumption, macronutrient consumption distribution, food preferences, and satiety responsiveness have been investigated as possible mechanisms with some evidence of association with obesity promoting genes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2006.04.016", "ISSN" : "0031-9384", "PMID" : "16750228", "abstract" : "BACKGROUND: There is persisting interest in the idea that taste preferences are heritable characteristics, but few twin studies have found evidence for a significant genetic component. Small sample sizes and idiosyncratic selection of foods may have contributed to the negative results. We hypothesized that using a larger twin sample and empirical groupings of food types, would give stronger evidence for the heritability of food preferences. OBJECTIVE: We examined the heritability of preferences for four food groups in a sample of young twins. DESIGN: We administered a food preference questionnaire with 95 foods to 214 mothers of same-sex twin pairs (103 monozygotic and 111 dizygotic pairs) aged 4 to 5. 18 foods were excluded because they had been tried by fewer than 25% of the children. Foods were grouped into 'Vegetables', 'Fruits', 'Desserts' and 'Meat and Fish' on the basis of a factor analysis of the preference data. Genetic analyses were carried out on mean liking across these four groups, using model fitting techniques. RESULTS: Over all 77 foods, MZ correlations were higher than DZ correlations for 72 of them, with a higher mean MZ correlation (r = 0.76) than DZ correlation (r = 0.56). Using model fitting techniques with the factor scores, significant heritability estimates were obtained for all four food groups. Heritability was modest for dessert foods (0.20), moderate for vegetables (0.37) and fruits (0.51), and high for liking for protein foods (0.78). Shared environmental effects were strong for desserts, fruits and vegetables, while non-shared environmental influences were low for all four food groups. CONCLUSIONS: These results provide strong evidence for modest heritability of food preferences when using empirically-derived groupings of foods.", "author" : [ { "dropping-particle" : "", "family" : "Breen", "given" : "Fiona M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiol Behav", "id" : "ITEM-1", "issue" : "4-5", "issued" : { "date-parts" : [ [ "2006", "7", "30" ] ] }, "page" : "443-447", "title" : "Heritability of food preferences in young children.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3945/jn.108.087668.TABLE", "author" : [ { "dropping-particle" : "", "family" : "Hasselbalch", "given" : "Ann Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitmann", "given" : "Berit L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "Thorkild I A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Nutrition", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2406-2412", "title" : "Studies of twins indicate that genetics influence dietary intake", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3945/ajcn.111.023671.Am", "author" : [ { "dropping-particle" : "", "family" : "Llewellyn", "given" : "Clare H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Jaarsveld", "given" : "Cornelia H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Abigail", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Inherited behavioral susceptibility to adiposity in infancy : a multivariate genetic analysis of appetite and weight in the Gemini birth cohort 1 \u2013 3", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/oby.20592", "ISSN" : "1930-739X", "PMID" : "23929626", "abstract" : "OBJECTIVE: Many confirmed genetic loci for obesity are expressed in regions of the brain that regulate energy intake and reward-seeking behavior. Whether these loci contribute to the development of specific eating behaviors has not been investigated. The relationship between a genetic susceptibility to obesity and cognitive restraint, uncontrolled and emotional eating was examined. METHODS: Eating behavior and body mass index (BMI) were determined by questionnaires for 1471 men and 2381 women from two US cohorts. Genotypes were extracted from genome-wide scans and a genetic-risk score (GRS) derived from 32 obesity-loci was calculated. RESULTS: The GRS was positively associated with emotional and uncontrolled eating (P<0.002). In exploratory analysis, BMI-increasing variants of MTCH2, TNNI3K, and ZC3H4 were positively associated with emotional eating and those of TNNI3K and ZC3H4 were positively associated with uncontrolled eating. The BMI-increasing variant of FTO was positively and those of LRP1B and TFAP2B were inversely associated with cognitive restraint. These associations for single SNPs were independent of BMI but were not significant after multiple-testing correction. CONCLUSIONS: An overall genetic susceptibility to obesity may also extend to eating behaviors. The link between specific loci and obesity may be mediated by eating behavior but larger studies are warranted to confirm these results.", "author" : [ { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimm", "given" : "Eric B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curhan", "given" : "Gary C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "135-141", "title" : "Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Breen et al. 2006; Hasselbalch et al. 2008; Llewellyn et al. 2012; Cornelis et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Breen et al. 2006; Hasselbalch et al. 2008; Llewellyn et al. 2012; Cornelis et al. 2014). In addition to exploring the association of already known obesity promoting genes with food consumption parameters, examining the evolutionary history of obesity and other disordered eating patterns may also shed light on possible mechanisms. Literature Review 2.1 Heritability of obesityTo determine the heritability of traits or diseases, including obesity, four contributing factors that lead to the development of the phenotype are quantified ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrg932", "ISSN" : "1471-0056", "PMID" : "12415317", "abstract" : "Twin studies have been a valuable source of information about the genetic basis of complex traits. To maximize the potential of twin studies, large, worldwide registers of data on twins and their relatives have been established. Here, we provide an overview of the current resources for twin research. These can be used to obtain insights into the genetic epidemiology of complex traits and diseases, to study the interaction of genotype with sex, age and lifestyle factors, and to study the causes of co-morbidity between traits and diseases. Because of their design, these registers offer unique opportunities for selected sampling for quantitative trait loci linkage and association studies.", "author" : [ { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busjahn", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Review Genetics", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2002", "11" ] ] }, "page" : "872-882", "title" : "Classical twin studies and beyond", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Boomsma et al. 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Boomsma et al. 2002). These factors and their symbols include ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1467-5463", "PMID" : "12139432", "abstract" : "The classical twin study is the most popular design in behavioural genetics. It has strong roots in biometrical genetic theory, which allows predictions to be made about the correlations between observed traits of identical and fraternal twins in terms of underlying genetic and environmental components. One can infer the relative importance of these 'latent' factors (model parameters) by structural equation modelling (SEM) of observed covariances of both twin types. SEM programs estimate model parameters by minimising a goodness-of-fit function between observed and predicted covariance matrices, usually by the maximum-likelihood criterion. Likelihood ratio statistics also allow the comparison of fit of different competing models. The program Mx, specifically developed to model genetically sensitive data, is now widely used in twin analyses. The flexibility of Mx allows the modelling of multivariate data to examine the genetic and environmental relations between two or more phenotypes and the modelling to categorical traits under liability-threshold models.", "author" : [ { "dropping-particle" : "V", "family" : "Rijsdijk", "given" : "Fr\u00fchling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Briefings in bioinformatics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "6" ] ] }, "page" : "119-133", "title" : "Analytic approaches to twin data using structural equation models", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rijsdijk and Sham 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rijsdijk and Sham 2002):A: Additive genetic influences which are calculated as the sum of the effect of each allele at all loci which influence the phenotype C: Shared environmental factors which are influences that would be common to members of a family such as socioeconomic statusD: Non-additive genetic influences which include the interaction between alleles at the same locus (dominance) or at different loci (epistasis)E: Unique environmental influences such as differences in parental treatment, prenatal environmental, and life eventsTwin studies are a frequently used method to determine heritability taking advantage of the nearly 100% shared genetic data for monozygotic (MZ) twins. Theoretically, MZ pairs do not differ from one another genetically (A and D) and also have the same shared environmental factors (C), therefore the difference in phenotypic traits can be attributed to unique environmental influences (E) (Rijsdijk & Sham, 2002). Like other sibling pairs dizygotic twins (DZ) only share 50% of their genetic data, however are assumed to have the same shared environment (C) and for the individual environment (E) to vary to the same extent as is observed in MZ pairs (Rijsdijk & Sham, 2002). Using the assumption that the unique environment (E) contributes to the development of the phentoype of interest equally in MZ and DZ pairs, comparing the correlation of a phenotype in MZ pairs versus DZ pairs allows for an estimate of heritability as the difference in correlation should be attributable to genetics, both additive and non-additive effects ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/nrg932", "ISSN" : "1471-0056", "PMID" : "12415317", "abstract" : "Twin studies have been a valuable source of information about the genetic basis of complex traits. To maximize the potential of twin studies, large, worldwide registers of data on twins and their relatives have been established. Here, we provide an overview of the current resources for twin research. These can be used to obtain insights into the genetic epidemiology of complex traits and diseases, to study the interaction of genotype with sex, age and lifestyle factors, and to study the causes of co-morbidity between traits and diseases. Because of their design, these registers offer unique opportunities for selected sampling for quantitative trait loci linkage and association studies.", "author" : [ { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busjahn", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Review Genetics", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2002", "11" ] ] }, "page" : "872-882", "title" : "Classical twin studies and beyond", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Boomsma et al. 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Boomsma et al. 2002). The most straightforward method of calculating heritability is Falconer’s formula which subtracts the phenotypic correlation in DZ pairs from the phenotypic correlation in MZ pairs and multiplies the result by two [H2= 2(rMZ – 2DZ)] (Rijsdijk & Sham, 2002). Family studies are also used to determine the heritability of phenotypes. Genotypic data can be collected using either genetic marker data or estimates of the expected genetic relatedness based upon the relationship between the two individuals. Creating a regression model of the genetic relatedness and the phenotypic trait of interest allows for an estimate of heritability ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev-genet-111212-133258.Estimation", "author" : [ { "dropping-particle" : "", "family" : "Vinkhuyzen", "given" : "Anna AE", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wrap", "given" : "Naomi R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yang", "given" : "Jian", "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" : "Annu Rev Genet", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "75-95", "title" : "Estimation and partioning of heritability in human populations using whole genome analysis methods", "type" : "article-journal", "volume" : "47" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Vinkhuyzen et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Vinkhuyzen et al. 2014). Modelling can also be used in twin studies, however models are poorly equipped to determine the non-additive genetic component (D) because non-additive genetic factors are confounded with shared environment and therefore cannot be estimated in the same model ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fendo.2012.00029", "ISSN" : "1664-2392", "PMID" : "22645519", "abstract" : "Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.", "author" : [ { "dropping-particle" : "", "family" : "Elks", "given" : "Cathy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "" } ], "container-title" : "Frontiers in Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "29", "title" : "Variability in the heritability of body mass index: a systematic review and meta-regression", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Elks et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Elks et al. 2012). Classic twin studies also have some limitations. The assumptions that gene-environment correlations and interactions are minimal as well as assuming that the amount of variance explained by environmental factors is identical in MZ and DZ pairs are questioned ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1467-5463", "PMID" : "12139432", "abstract" : "The classical twin study is the most popular design in behavioural genetics. It has strong roots in biometrical genetic theory, which allows predictions to be made about the correlations between observed traits of identical and fraternal twins in terms of underlying genetic and environmental components. One can infer the relative importance of these 'latent' factors (model parameters) by structural equation modelling (SEM) of observed covariances of both twin types. SEM programs estimate model parameters by minimising a goodness-of-fit function between observed and predicted covariance matrices, usually by the maximum-likelihood criterion. Likelihood ratio statistics also allow the comparison of fit of different competing models. The program Mx, specifically developed to model genetically sensitive data, is now widely used in twin analyses. The flexibility of Mx allows the modelling of multivariate data to examine the genetic and environmental relations between two or more phenotypes and the modelling to categorical traits under liability-threshold models.", "author" : [ { "dropping-particle" : "V", "family" : "Rijsdijk", "given" : "Fr\u00fchling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Briefings in bioinformatics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "6" ] ] }, "page" : "119-133", "title" : "Analytic approaches to twin data using structural equation models", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rijsdijk and Sham 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rijsdijk and Sham 2002). Making these assumptions increases the risk that heritability estimates are artificially inflated by incorrectly attributing the contribution of these factors to genetics ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "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-1", "issue" : "7265", "issued" : { "date-parts" : [ [ "2009", "10", "8" ] ] }, "page" : "747-753", "publisher" : "Nature Publishing Group", "title" : "Finding the missing heritability of complex diseases", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Manolio et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Manolio et al. 2009).The study design can have a substantial impact on heritability estimates. A recent meta-analysis of studies investigating BMI heritability found that in 88 independent twin studies (n=140,525), heritability estimates ranged from 0.47 to 0.90 while the estimates from 27 family studies (n=42,968) were lower, ranging from 0.24 to 0.81 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fendo.2012.00029", "ISSN" : "1664-2392", "PMID" : "22645519", "abstract" : "Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.", "author" : [ { "dropping-particle" : "", "family" : "Elks", "given" : "Cathy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "" } ], "container-title" : "Frontiers in Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "29", "title" : "Variability in the heritability of body mass index: a systematic review and meta-regression", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Elks et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Elks et al. 2012). Another meta-analysis estimated the heritability to be 0.20 to 0.80 using data from family studies and 0.20 to 0.60 from adoption studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0001-8244", "PMID" : "9519560", "abstract" : "We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent-offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent-offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared environment, and special twin and MZ twin environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin environment, thereby supporting the equal environment assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.", "author" : [ { "dropping-particle" : "", "family" : "Maes", "given" : "H H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neale", "given" : "M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eaves", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Behavior genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1997", "7" ] ] }, "page" : "325-51", "title" : "Genetic and environmental factors in relative body weight and human adiposity.", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Maes et al. 1997)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Maes et al. 1997). Though the assumption that the amount of variance explained by environmental factors is the same in MZ and DZ pairs has been criticized for inflating heritability estimates ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1467-5463", "PMID" : "12139432", "abstract" : "The classical twin study is the most popular design in behavioural genetics. It has strong roots in biometrical genetic theory, which allows predictions to be made about the correlations between observed traits of identical and fraternal twins in terms of underlying genetic and environmental components. One can infer the relative importance of these 'latent' factors (model parameters) by structural equation modelling (SEM) of observed covariances of both twin types. SEM programs estimate model parameters by minimising a goodness-of-fit function between observed and predicted covariance matrices, usually by the maximum-likelihood criterion. Likelihood ratio statistics also allow the comparison of fit of different competing models. The program Mx, specifically developed to model genetically sensitive data, is now widely used in twin analyses. The flexibility of Mx allows the modelling of multivariate data to examine the genetic and environmental relations between two or more phenotypes and the modelling to categorical traits under liability-threshold models.", "author" : [ { "dropping-particle" : "V", "family" : "Rijsdijk", "given" : "Fr\u00fchling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Briefings in bioinformatics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "6" ] ] }, "page" : "119-133", "title" : "Analytic approaches to twin data using structural equation models", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rijsdijk and Sham 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rijsdijk and Sham 2002), a study conducted in 93 MZ pairs raised separately found that the intra-pair correlation for BMI in MZ pairs reared apart was 0.70 for men and 0.66 for females. For MZ pairs reared apart, there is no shared environment (C) and the variance explained by unique environmental influences can be correctly assumed to be appropriately equal in the separated twins. In this unique situation, the intra-pair correlations are estimates of the amount of the variance explained by only genetic factors. The same study used a classical twin design with MZ (n=154) and DZ (n=208) pairs to provide a heritability estimate of 0.82 for males and 0.78 for females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Stunkard", "given" : "A.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "J.R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McClearn", "given" : "Gerald E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "1483-1487", "title" : "The body mass index of twins who have been reared apart", "type" : "article-journal", "volume" : "322" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Stunkard et al. 1990)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Stunkard et al. 1990). The difference in heritability estimates indicates that the classic twin design may have provided inflated heritability estimates due to confounding from gene-environment correlations and interactions ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1467-5463", "PMID" : "12139432", "abstract" : "The classical twin study is the most popular design in behavioural genetics. It has strong roots in biometrical genetic theory, which allows predictions to be made about the correlations between observed traits of identical and fraternal twins in terms of underlying genetic and environmental components. One can infer the relative importance of these 'latent' factors (model parameters) by structural equation modelling (SEM) of observed covariances of both twin types. SEM programs estimate model parameters by minimising a goodness-of-fit function between observed and predicted covariance matrices, usually by the maximum-likelihood criterion. Likelihood ratio statistics also allow the comparison of fit of different competing models. The program Mx, specifically developed to model genetically sensitive data, is now widely used in twin analyses. The flexibility of Mx allows the modelling of multivariate data to examine the genetic and environmental relations between two or more phenotypes and the modelling to categorical traits under liability-threshold models.", "author" : [ { "dropping-particle" : "V", "family" : "Rijsdijk", "given" : "Fr\u00fchling", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Pak C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Briefings in bioinformatics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "6" ] ] }, "page" : "119-133", "title" : "Analytic approaches to twin data using structural equation models", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rijsdijk and Sham 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rijsdijk and Sham 2002). The study supplemented their results by using maximum-likelihood model fitting analyses yielding heritability estimates of 0.74 for males and 0.69 for females. The similarities between these estimates and those provided through the twins reared apart support the use of modeling techniques for estimated heritability. The study was also the first to show that shared environment has a very modest effect on the variation in BMI ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Stunkard", "given" : "A.J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "J.R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McClearn", "given" : "Gerald E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New England Journal of Medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1990" ] ] }, "page" : "1483-1487", "title" : "The body mass index of twins who have been reared apart", "type" : "article-journal", "volume" : "322" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Stunkard et al. 1990)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Stunkard et al. 1990).The broad range of heritability estimates for BMI can in part be explained by different study methodologies including family studies and twin studies, different statistical procedures such as using Falconer’s formula versus various modeling techniques, errors in phenotyping, or the incorrect classification of MZ and DZ pairs. From the most recent meta-analysis, the median heritability estimate from twin studies was 0.75 and 0.46 for family studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fendo.2012.00029", "ISSN" : "1664-2392", "PMID" : "22645519", "abstract" : "Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.", "author" : [ { "dropping-particle" : "", "family" : "Elks", "given" : "Cathy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "" } ], "container-title" : "Frontiers in Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "29", "title" : "Variability in the heritability of body mass index: a systematic review and meta-regression", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Elks et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Elks et al. 2012) indicating that that genes explain a moderate to high degree of the variability in obesity. Heritability estimates for BMI are also age-dependent, increasing with age and reaching a plateau at young adulthood ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2009.177", "ISSN" : "1476-5497", "PMID" : "19752881", "abstract" : "In this systematic review, we aimed to collect together all previous twin and adoption studies on childhood and adolescent obesity up to the age of 18 years. Using several sources, we identified nine twin and five adoption studies; all of these studies had used relative weight as an indicator of obesity. Except the two twin studies from the Korean population, all studies represented Caucasian populations. In a meta-analysis of these twin studies, we found that genetic factors had a strong effect on the variation of body mass index (BMI) at all ages. The common environmental factors showed a substantial effect in mid-childhood, but this effect disappeared at adolescence. Adoption studies supported the role of family environment in childhood obesity as correlations were found between adoptees and adoptive parents; however, correlations were substantially stronger between parents and their biological offspring, further supporting the importance of genetic factors. In the future, more studies implementing genetic and environmental measures into twin models are needed as they allow estimation of the proportion of total genetic variation explained by candidate genes and analyses of gene-environment interactions. More studies of genetic architecture in non-Caucasian populations, of gene-environment interactions, and of body composition and body fat distribution are needed.", "author" : [ { "dropping-particle" : "", "family" : "Silventoinen", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rokholm", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "T I A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Obes", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "29-40", "title" : "The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3389/fendo.2012.00029", "ISSN" : "1664-2392", "PMID" : "22645519", "abstract" : "Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.", "author" : [ { "dropping-particle" : "", "family" : "Elks", "given" : "Cathy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "" } ], "container-title" : "Frontiers in Endocrinology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "29", "title" : "Variability in the heritability of body mass index: a systematic review and meta-regression", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1159/000219675", "ISSN" : "1662-4025", "PMID" : "20054225", "abstract" : "The persistence of obesity from early childhood to late middle age is well known. We reviewed the results from existing genetic studies on tracking of BMI to discover how much genetic and environmental factors contribute to this tracking of obesity. In total, we found 5 genetic longitudinal studies on childhood obesity and 8 on obesity in adulthood. One was an adoption study, 3 were family studies, and 9 were twin studies. All were based on Caucasian populations, and one included genetic level information (the FTO gene). Strong genetic continuity in BMI was found from early childhood to onset of adulthood. Although new genetic factors started to affect BMI during the growth period, genetic correlations remained high. Evidence of the effect of common environment on the tracking of BMI during childhood was also found. The heritability estimates reported in twin studies ranged from 0.57 to 0.86 for the trend of BMI from early adulthood to late middle age. The three family studies gave lower estimates. Important unresolved questions are the genetics of BMI change in old age, the genetics of body composition change, the genetic architecture of tracking of obesity in ethnic groups other than Caucasians, and the interplay between genes and environment underlying the development and tracking of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Silventoinen", "given" : "Karri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur J Obes", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "page" : "196-202", "title" : "Genetics of tracking of body mass index from birth to late middle age: evidence from twin and family studies", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Silventoinen and Kaprio 2009; Silventoinen et al. 2010; Elks et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Silventoinen and Kaprio 2009; Silventoinen et al. 2010; Elks et al. 2012). Based on this information, exploration into the specific genes that may be contributing to obesity risk is warranted. 2.2 Heritability of eating characteristics Increased total energy intake is a well-established risk factor for obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/10408390903372599", "ISSN" : "1549-7852", "PMID" : "19960394", "abstract" : "The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic.", "author" : [ { "dropping-particle" : "", "family" : "McAllister", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dhurandhar", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keith", "given" : "Scott W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aronne", "given" : "Louis J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barger", "given" : "Jamie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baskin", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benca", "given" : "Ruth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biggio", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boggiano", "given" : "Mary M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eisenmann", "given" : "Joe C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elobeid", "given" : "Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontaine", "given" : "Kevin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluckman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanlon", "given" : "Erin C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katzmarzyk", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietrobelli", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Redden", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruden", "given" : "Douglas M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Chenxi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterland", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Suzanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Critical Reviews in Food Science and Nutrition", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2009", "11" ] ] }, "page" : "868-913", "title" : "Ten putative contributors to the obesity epidemic", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(McAllister et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(McAllister et al. 2009), however many other eating behaviours are similarly found to be associated with body weight or increased caloric consumption. Strong epidemiological evidence supports a positive association between dietary fat consumption and weight ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2004.08.039", "ISSN" : "0031-9384", "PMID" : "15621059", "abstract" : "The First Law of Thermodynamics provides a framework for understanding the imbalance between energy intake and expenditure that produces obesity, but it does not help understand the role of genetics, the regulation of food intake, the distribution of body fat, the mechanisms by which diets work or the mechanism by which portion control has gotten out of control. In animals, increasing dietary fat increases body fat, and it is unlikely that humans escape this important biological rule. In epidemiological studies, increasing dietary fat is associated with increased prevalence of obesity probably by increasing the intake of energy dense foods. In the National Weight Loss Registry, three things were associated with weight loss: continued monitoring of food intake, lowering dietary fat intake, and increased exercise. The relation of dietary fat is most evident when physical activity is low. The speed of adaptation to dietary fat is increased by exercise. When dietary fat is reduced, weight is lost, but weight loss eventually plateaus. The rate of weight loss during the initial phase is about 1.6 g/day for each 1% decrease in fat intake. When dietary fat is replaced with olestra to reduce fat intake from 33% to 25% in obese men, weight loss continues for about 9 months reaching a maximum of nearly 6% of body weight and a loss of 18% of initial body fat. In the control group with a 25% reduced-fat diet, weight loss stopped after 3 months and was regained over the next 6 months, indicating the difficulty of adhering to a conventional low-fat diet. Thus, dietary fat is an important contributor to obesity in some people.", "author" : [ { "dropping-particle" : "", "family" : "Bray", "given" : "George a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paeratakul", "given" : "Sahasporn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Popkin", "given" : "Barry M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & behavior", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2004", "12", "30" ] ] }, "page" : "549-555", "title" : "Dietary fat and obesity: a review of animal, clinical and epidemiological studies.", "type" : "article-journal", "volume" : "83" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bray et al. 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bray et al. 2004) and a negative association between dietary carbohydrate consumption and weight ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jada.2007.07.011", "ISSN" : "0002-8223", "PMID" : "17904937", "abstract" : "The increased prevalence of overweight and obesity in the United States since approximately 1980 is temporally associated with an increase in carbohydrate intake, with no appreciable change in absolute intake of fat. Despite speculation that both carbohydrate quantity and quality have contributed significantly to excess weight gain, the relationship between carbohydrate intake and body mass index (BMI) is controversial. A review of relevant literature indicates that most epidemiologic studies show an inverse relationship between carbohydrate intake and BMI, even when controlling for potential confounders. These observational studies are supported by results from a number of dietary intervention studies wherein modest reductions in body weight were observed with an ad libitum, low-fat, high-carbohydrate diet without emphasis on energy restriction or weight loss. With few exceptions, high glycemic load is associated with lower BMI, even when adjusted for total energy intake. Data on the association between glycemic index and BMI are not as consistent, with more studies showing either no association or an inverse relationship, rather than a positive relationship. Whole-grain intake is generally inversely associated with BMI; refined grain intake is not. Because overall dietary quality tends to be higher for high-carbohydrate diets, a low-fat dietary strategy with emphasis on fiber-rich carbohydrates, particularly cereal fiber, may be beneficial for health and weight control.", "author" : [ { "dropping-particle" : "", "family" : "Gaesser", "given" : "Glenn A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of the American Dietetic Association", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2007", "10" ] ] }, "page" : "1768-1780", "title" : "Carbohydrate quantity and quality in relation to body mass index", "type" : "article-journal", "volume" : "107" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gaesser 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gaesser 2007). In both adult and adolescent populations there is a growing body of evidence that food responsiveness including liking of food and satiety responsiveness, eating in the absence of hunger, disinhibition, and impulsivity/self-control are associated with BMI and overall food/energy intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "French", "given" : "Simone A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H", "given" : "Epstein Leonard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "JEffery", "given" : "Robert W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blundell", "given" : "John E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Appetite", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "541-549", "title" : "Eating behavior dimensions. Associations with energy intake and body weight. A review", "type" : "article-journal", "volume" : "59" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(French et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(French et al. 2012). Because of the association of these eating characteristics with weight the same techniques used to determine the heritability of obesity have also been used to determine the hereditably of food consumption behaviour. 2.2.1 Energy consumption and macronutrient distributionA strong positive association between energy intake and weight as well as the difference in energy density of macronutrients have led researchers to investigate if consumption levels are a heritable trait. A study conducted in twin pairs from the Quebec Newborn Twin Study (n=379) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2013.05.039", "ISSN" : "1873-507X", "PMID" : "23748099", "abstract" : "BACKGROUND: Few twin studies have examined nutrition-related phenotypes among children, and none has investigated energy and macronutrient intakes. OBJECTIVE: The objective was to quantify genetic and environmental influences on variations in energy and macronutrient intakes among children aged 9 years. DESIGN: We conducted a nutrition study among children participating in the Quebec Newborn Twin Study, a population-based birth cohort of twins. We derived dietary data from two multiple-pass 24-hour dietary recalls with a parent and his or her child. The analysis employed a classic twin study design and used data from 379 twin pairs. RESULTS: Univariate analyses indicate that heritability for mean daily energy (kcal) and macronutrient (g) intakes was moderate, ranging from 0.34 (95% CI: 0.22, 0.46) to 0.42 (0.31, 0.53). Genetic effects also accounted for 0.28 (0.16, 0.40) of the variance in percent of energy from lipids, while only environmental (shared and unique) effects accounted for the variance in percent of energy from proteins and carbohydrates. The shared environment did not contribute to variations in daily intakes for most of the nutritional variables under study. Multivariate analyses suggest the presence of macronutrient-specific genetic influences for lipids and carbohydrates, estimated at 0.12 (0.04, 0.19) and 0.20 (0.11, 0.29) respectively. CONCLUSIONS: The unique environment (i.e., not shared by family members) has the largest influence on variances in daily energy and macronutrient intakes in 9-year-old children. This finding underscores the need to take obesogenic environments into account when planning dietary interventions for younger populations.", "author" : [ { "dropping-particle" : "", "family" : "Dubois", "given" : "Lise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diasparra", "given" : "Maikol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00e9dard", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontaine-Bisson", "given" : "B\u00e9n\u00e9dicte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9russe", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tremblay", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boivin", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & Behavior", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "7", "2" ] ] }, "page" : "30-37", "publisher" : "Elsevier Inc.", "title" : "Gene-environment contributions to energy and macronutrient intakes in 9-year-old children: results from the Quebec Newborn Twin Study", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dubois et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dubois et al. 2013) found that the heritability of mean energy intake measured in kilocalories (kcal) is 0.42 (95% confidence interval 0.31 to 0.53), while the heritability of intake in grams of protein, fat, and carbohydrates is 0.35 (0.24 to 0.47), 0.34 (0.22 to 0.46), and 0.42 (0.31 to 0.53) respectively. The study also investigated the percentage of total daily calories from each macronutrient with only the percentage of calories from fat having significant heritability with an estimate of 0.28 (0.16 to 0.40). Studies conducted in adult populations including twin pairs (n=600) from the Danish Twin Registry, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/jn.108.087668.TABLE", "author" : [ { "dropping-particle" : "", "family" : "Hasselbalch", "given" : "Ann Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitmann", "given" : "Berit L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "Thorkild I A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Nutrition", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2406-2412", "title" : "Studies of twins indicate that genetics influence dietary intake", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hasselbalch et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hasselbalch et al. 2008), twins and non-related individuals from the Minnesota Study of Twins Reared Apart (MISTRA) (n=335) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0031-9384", "PMID" : "9817574", "abstract" : "A sample of 66 monozyogtic twins reared apart (MZA) and 51 dizygotic twins reared apart (DZA), and 101 nontwin individuals (mostly spouses of the twins) who participated in the Minnesota Study of Twins Reared Apart (MISTRA) from 1979 to 1995 completed a self-report food frequency questionnaire. Intraclass-correlations and model-fitting analyses indicated that approximately 30% of the variance in the self-report of diet was attributable to genetic factors, with random environmental factors and measurement error responsible for the remaining variance. Spouse correlations were moderate. To investigate the effects of living together during marriage, the absolute differences between husband and wife on the dietary variables with years of marriage were correlated. None of the correlations were significant. Hierarchical multiple regression analyses also indicated that no convergence occurred during marriage. These results suggest that sharing a current family environment exerts minimal influence on individual differences in self-reported diet.", "author" : [ { "dropping-particle" : "", "family" : "Hur", "given" : "Y M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouchard", "given" : "T J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eckert", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & Behavior", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1998", "7" ] ] }, "page" : "629-636", "title" : "Genetic and environmental influences on self-reported diet: a reared-apart twin study", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hur et al. 1998)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hur et al. 1998), and families from the San Antonio Family Heart Study (n=1431) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9165", "PMID" : "15531694", "abstract" : "BACKGROUND: Obesity is generally accompanied by increased food intake.\n\nOBJECTIVE: We sought to identify the genes influencing variation in dietary macronutrient intakes in Mexican Americans.\n\nDESIGN: We conducted a genome-wide scan by using data derived from food-frequency questionnaires in 816 participants from the San Antonio Family Heart Study. Household effect was simultaneously estimated in a variance component model with the use of SOLAR.\n\nRESULTS: All dietary intake measures (total calories, proteins, fat, saturated fat, monounsaturated fat, polyunsaturated fat, carbohydrates, and sucrose) were moderately heritable. Household effect was insignificant except on total calories and sucrose. Suggestive evidence of linkage with saturated fat intake was found on chromosome 2p22 near marker D2S1346 [logarithm of odds (LOD) = 2.62]. Intakes of total calories, fat, protein, and monounsaturated fat were also suggestively linked to the same marker. A significant linkage signal on chromosome 2p22 for leptin concentrations and fat mass was localized in this population, so we used leptin or fat mass as a covariate. Multipoint LOD scores for saturated fat dropped to 1.27 and 1.90, respectively, which suggested that this region on chromosome 2p contributes to both saturated fat intake and body adiposity. This chromosomal region contains the proopiomelanocortin gene (POMC). However, 2 polymorphisms in exon 3 of the POMC gene showed no association with saturated fat intake.\n\nCONCLUSIONS: The results strengthen the hypothesis that chromosome 2p22 harbors genes that influence a variety of obesity-related phenotypes, including macronutrient intakes.", "author" : [ { "dropping-particle" : "", "family" : "Cai", "given" : "Guowen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cole", "given" : "Shelley a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bastarrachea", "given" : "Raul a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bastarrachea-Sosa", "given" : "Raul a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maccluer", "given" : "Jean W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blangero", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Comuzzie", "given" : "Anthony G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of clinical nutrition", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2004", "11" ] ] }, "page" : "1410-4", "title" : "Quantitative trait locus determining dietary macronutrient intakes is located on human chromosome 2p22.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1047-2797", "PMID" : "12559672", "abstract" : "PURPOSE: To evaluate the extent to which levels of physical activity and nutrient intake aggregate in families, and secondarily, to assess the repeatability of these behavioral measures over a 5-year period.\n\nMETHODS: Measurements were obtained in a population-based sample consisting of 1364 members of 42 large Mexican American families. Nutrient intake was assessed by a food frequency questionnaire validated for use in this population. Usual level of physical activity was estimated using a 7-day recall questionnaire.\n\nRESULTS: Correlations between baseline (obtained 1992-1995) and follow-up (obtained 1996 to 2000) measures of all behaviors were highly significant (p < 0.001), ranging from 0.24 for % of calories derived from fat to 0.44 for % of calories derived from alcohol. Familial effects, estimated using variance component methods, were stronger when modeled as a genetic heritability than as a shared household effect; as a heritability they accounted for a significant portion of the total variation of all traits (9% for physical activity levels, p < 0.05; and 13-26% for nutrient intake, p < 0.001 for all).\n\nCONCLUSIONS: Measurements of physical activity and dietary behaviors in this population tracked over 5 years, and there was a significant degree of aggregation of these behaviors within families. Understanding the sources of these family effects may facilitate efforts to improve cardiovascular health.", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rainwater", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsueh", "given" : "Wen-Chi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kennedy", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stern", "given" : "Michael P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maccluer", "given" : "Jean W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of epidemiology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2003", "2" ] ] }, "page" : "128-35", "title" : "Familial aggregation of nutrient intake and physical activity: results from the San Antonio Family Heart Study.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mitchell et al. 2003; Cai et al. 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mitchell et al. 2003; Cai et al. 2004) have come to similar conclusions. The Danish Twin Registry ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/jn.108.087668.TABLE", "author" : [ { "dropping-particle" : "", "family" : "Hasselbalch", "given" : "Ann Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitmann", "given" : "Berit L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "Thorkild I A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Nutrition", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2406-2412", "title" : "Studies of twins indicate that genetics influence dietary intake", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hasselbalch et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hasselbalch et al. 2008) produced heritability estimates for the additive genetic effect of 0.38 (0.24 to 0.51) in males and 0.32 (0.12 to 0.48) in females for total energy consumption, 0.28 (0.12 to 0.43) in males and 0.01 (0.00 to 0.39) in females for percentage of calories from protein, 0.36 (0.22 to 0.49) in males and 0.49 (0.35 to 0.61) in females for percentage of calories from carbohydrates, and 0.01 (0.00 to 0.45) in males and 0.01 (0.00 to 0.57) from percentage of calories in fat. For the variables in which low heritability was found for additive genetic effects, there was a moderate to strong contribution of non-additive genetic effects ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/jn.108.087668.TABLE", "author" : [ { "dropping-particle" : "", "family" : "Hasselbalch", "given" : "Ann Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitmann", "given" : "Berit L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "Thorkild I A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Nutrition", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2406-2412", "title" : "Studies of twins indicate that genetics influence dietary intake", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hasselbalch et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hasselbalch et al. 2008). In MISTRA ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0031-9384", "PMID" : "9817574", "abstract" : "A sample of 66 monozyogtic twins reared apart (MZA) and 51 dizygotic twins reared apart (DZA), and 101 nontwin individuals (mostly spouses of the twins) who participated in the Minnesota Study of Twins Reared Apart (MISTRA) from 1979 to 1995 completed a self-report food frequency questionnaire. Intraclass-correlations and model-fitting analyses indicated that approximately 30% of the variance in the self-report of diet was attributable to genetic factors, with random environmental factors and measurement error responsible for the remaining variance. Spouse correlations were moderate. To investigate the effects of living together during marriage, the absolute differences between husband and wife on the dietary variables with years of marriage were correlated. None of the correlations were significant. Hierarchical multiple regression analyses also indicated that no convergence occurred during marriage. These results suggest that sharing a current family environment exerts minimal influence on individual differences in self-reported diet.", "author" : [ { "dropping-particle" : "", "family" : "Hur", "given" : "Y M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouchard", "given" : "T J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eckert", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & Behavior", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1998", "7" ] ] }, "page" : "629-636", "title" : "Genetic and environmental influences on self-reported diet: a reared-apart twin study", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hur et al. 1998)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hur et al. 1998) the additive effects of genetics accounted for an average of 0.22 of the variability of nutrients investigated including 0.32 (0.10 to 0.51) for caloric consumption, 0.40 (0.20 to 0.57) for calories/kg consumed, 0.16 (0.00 to 0.37) for protein in grams, 0.35 (0.14 to 0.52) for fat in grams, and 0.25 (0.03 to 0.45) of carbohydrates in grams. In the San Antonio Family Heart Study ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9165", "PMID" : "15531694", "abstract" : "BACKGROUND: Obesity is generally accompanied by increased food intake.\n\nOBJECTIVE: We sought to identify the genes influencing variation in dietary macronutrient intakes in Mexican Americans.\n\nDESIGN: We conducted a genome-wide scan by using data derived from food-frequency questionnaires in 816 participants from the San Antonio Family Heart Study. Household effect was simultaneously estimated in a variance component model with the use of SOLAR.\n\nRESULTS: All dietary intake measures (total calories, proteins, fat, saturated fat, monounsaturated fat, polyunsaturated fat, carbohydrates, and sucrose) were moderately heritable. Household effect was insignificant except on total calories and sucrose. Suggestive evidence of linkage with saturated fat intake was found on chromosome 2p22 near marker D2S1346 [logarithm of odds (LOD) = 2.62]. Intakes of total calories, fat, protein, and monounsaturated fat were also suggestively linked to the same marker. A significant linkage signal on chromosome 2p22 for leptin concentrations and fat mass was localized in this population, so we used leptin or fat mass as a covariate. Multipoint LOD scores for saturated fat dropped to 1.27 and 1.90, respectively, which suggested that this region on chromosome 2p contributes to both saturated fat intake and body adiposity. This chromosomal region contains the proopiomelanocortin gene (POMC). However, 2 polymorphisms in exon 3 of the POMC gene showed no association with saturated fat intake.\n\nCONCLUSIONS: The results strengthen the hypothesis that chromosome 2p22 harbors genes that influence a variety of obesity-related phenotypes, including macronutrient intakes.", "author" : [ { "dropping-particle" : "", "family" : "Cai", "given" : "Guowen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cole", "given" : "Shelley a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bastarrachea", "given" : "Raul a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bastarrachea-Sosa", "given" : "Raul a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maccluer", "given" : "Jean W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blangero", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Comuzzie", "given" : "Anthony G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of clinical nutrition", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2004", "11" ] ] }, "page" : "1410-4", "title" : "Quantitative trait locus determining dietary macronutrient intakes is located on human chromosome 2p22.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1047-2797", "PMID" : "12559672", "abstract" : "PURPOSE: To evaluate the extent to which levels of physical activity and nutrient intake aggregate in families, and secondarily, to assess the repeatability of these behavioral measures over a 5-year period.\n\nMETHODS: Measurements were obtained in a population-based sample consisting of 1364 members of 42 large Mexican American families. Nutrient intake was assessed by a food frequency questionnaire validated for use in this population. Usual level of physical activity was estimated using a 7-day recall questionnaire.\n\nRESULTS: Correlations between baseline (obtained 1992-1995) and follow-up (obtained 1996 to 2000) measures of all behaviors were highly significant (p < 0.001), ranging from 0.24 for % of calories derived from fat to 0.44 for % of calories derived from alcohol. Familial effects, estimated using variance component methods, were stronger when modeled as a genetic heritability than as a shared household effect; as a heritability they accounted for a significant portion of the total variation of all traits (9% for physical activity levels, p < 0.05; and 13-26% for nutrient intake, p < 0.001 for all).\n\nCONCLUSIONS: Measurements of physical activity and dietary behaviors in this population tracked over 5 years, and there was a significant degree of aggregation of these behaviors within families. Understanding the sources of these family effects may facilitate efforts to improve cardiovascular health.", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rainwater", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsueh", "given" : "Wen-Chi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kennedy", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stern", "given" : "Michael P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maccluer", "given" : "Jean W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of epidemiology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2003", "2" ] ] }, "page" : "128-35", "title" : "Familial aggregation of nutrient intake and physical activity: results from the San Antonio Family Heart Study.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mitchell et al. 2003; Cai et al. 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mitchell et al. 2003; Cai et al. 2004), the heritability estimates were considerably lower, ranging from 0.09 to 0.21 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9165", "PMID" : "15531694", "abstract" : "BACKGROUND: Obesity is generally accompanied by increased food intake.\n\nOBJECTIVE: We sought to identify the genes influencing variation in dietary macronutrient intakes in Mexican Americans.\n\nDESIGN: We conducted a genome-wide scan by using data derived from food-frequency questionnaires in 816 participants from the San Antonio Family Heart Study. Household effect was simultaneously estimated in a variance component model with the use of SOLAR.\n\nRESULTS: All dietary intake measures (total calories, proteins, fat, saturated fat, monounsaturated fat, polyunsaturated fat, carbohydrates, and sucrose) were moderately heritable. Household effect was insignificant except on total calories and sucrose. Suggestive evidence of linkage with saturated fat intake was found on chromosome 2p22 near marker D2S1346 [logarithm of odds (LOD) = 2.62]. Intakes of total calories, fat, protein, and monounsaturated fat were also suggestively linked to the same marker. A significant linkage signal on chromosome 2p22 for leptin concentrations and fat mass was localized in this population, so we used leptin or fat mass as a covariate. Multipoint LOD scores for saturated fat dropped to 1.27 and 1.90, respectively, which suggested that this region on chromosome 2p contributes to both saturated fat intake and body adiposity. This chromosomal region contains the proopiomelanocortin gene (POMC). However, 2 polymorphisms in exon 3 of the POMC gene showed no association with saturated fat intake.\n\nCONCLUSIONS: The results strengthen the hypothesis that chromosome 2p22 harbors genes that influence a variety of obesity-related phenotypes, including macronutrient intakes.", "author" : [ { "dropping-particle" : "", "family" : "Cai", "given" : "Guowen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cole", "given" : "Shelley a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bastarrachea", "given" : "Raul a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bastarrachea-Sosa", "given" : "Raul a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maccluer", "given" : "Jean W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blangero", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Comuzzie", "given" : "Anthony G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American journal of clinical nutrition", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2004", "11" ] ] }, "page" : "1410-4", "title" : "Quantitative trait locus determining dietary macronutrient intakes is located on human chromosome 2p22.", "type" : "article-journal", "volume" : "80" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cai et al. 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cai et al. 2004) for total energy intake and grams of nutrients consumed per day, and between 0.13 to 0.26 for the percentage of total calories coming from macronutrients ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1047-2797", "PMID" : "12559672", "abstract" : "PURPOSE: To evaluate the extent to which levels of physical activity and nutrient intake aggregate in families, and secondarily, to assess the repeatability of these behavioral measures over a 5-year period.\n\nMETHODS: Measurements were obtained in a population-based sample consisting of 1364 members of 42 large Mexican American families. Nutrient intake was assessed by a food frequency questionnaire validated for use in this population. Usual level of physical activity was estimated using a 7-day recall questionnaire.\n\nRESULTS: Correlations between baseline (obtained 1992-1995) and follow-up (obtained 1996 to 2000) measures of all behaviors were highly significant (p < 0.001), ranging from 0.24 for % of calories derived from fat to 0.44 for % of calories derived from alcohol. Familial effects, estimated using variance component methods, were stronger when modeled as a genetic heritability than as a shared household effect; as a heritability they accounted for a significant portion of the total variation of all traits (9% for physical activity levels, p < 0.05; and 13-26% for nutrient intake, p < 0.001 for all).\n\nCONCLUSIONS: Measurements of physical activity and dietary behaviors in this population tracked over 5 years, and there was a significant degree of aggregation of these behaviors within families. Understanding the sources of these family effects may facilitate efforts to improve cardiovascular health.", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Braxton D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rainwater", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hsueh", "given" : "Wen-Chi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kennedy", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stern", "given" : "Michael P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maccluer", "given" : "Jean W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of epidemiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2003", "2" ] ] }, "page" : "128-35", "title" : "Familial aggregation of nutrient intake and physical activity: results from the San Antonio Family Heart Study.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mitchell et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mitchell et al. 2003). A potential cause of the lower heritability estimates from the San Antonio Family Heart Study compared to the other studies is that they used related individuals opposed to twins requiring different statistical methods to be employed to estimate heritability. Dietary estimation methods used in these studies such as food frequency questionnaires (FFQs) and 24 hour recalls also have a significant amount of error associated with them which could also lead to different estimates. 2.2.2 Food consumption patternsIn addition to assessing the heritability of the consumption of energy and macronutrients, studies have also investigated if certain dietary pattern types, for example diets high in fruits and vegetables, are heritable. In children, there is evidence that the types of food most commonly consumed are heritable. The MacArthur Longitudinal Study of Twins (n=792) found that using a 24 hour dietary recall, seven food categories investigated had significant heritability estimates, including an estimate of 0.79 for the consumption of peanut butter and jelly in males and 0.56 for the consumption of fish and lemons in females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Faith", "given" : "Myles S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rhea", "given" : "Sally Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Corley", "given" : "Robin P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hewitt", "given" : "John K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "903-911", "title" : "Genetic and shared environmental influences on children's 24-h food and beverage intake: sex differences at age 7 y", "type" : "article-journal", "volume" : "87" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Faith et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Faith et al. 2008). Using factor analysis on 77 food items, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2006.04.016", "ISSN" : "0031-9384", "PMID" : "16750228", "abstract" : "BACKGROUND: There is persisting interest in the idea that taste preferences are heritable characteristics, but few twin studies have found evidence for a significant genetic component. Small sample sizes and idiosyncratic selection of foods may have contributed to the negative results. We hypothesized that using a larger twin sample and empirical groupings of food types, would give stronger evidence for the heritability of food preferences. OBJECTIVE: We examined the heritability of preferences for four food groups in a sample of young twins. DESIGN: We administered a food preference questionnaire with 95 foods to 214 mothers of same-sex twin pairs (103 monozygotic and 111 dizygotic pairs) aged 4 to 5. 18 foods were excluded because they had been tried by fewer than 25% of the children. Foods were grouped into 'Vegetables', 'Fruits', 'Desserts' and 'Meat and Fish' on the basis of a factor analysis of the preference data. Genetic analyses were carried out on mean liking across these four groups, using model fitting techniques. RESULTS: Over all 77 foods, MZ correlations were higher than DZ correlations for 72 of them, with a higher mean MZ correlation (r = 0.76) than DZ correlation (r = 0.56). Using model fitting techniques with the factor scores, significant heritability estimates were obtained for all four food groups. Heritability was modest for dessert foods (0.20), moderate for vegetables (0.37) and fruits (0.51), and high for liking for protein foods (0.78). Shared environmental effects were strong for desserts, fruits and vegetables, while non-shared environmental influences were low for all four food groups. CONCLUSIONS: These results provide strong evidence for modest heritability of food preferences when using empirically-derived groupings of foods.", "author" : [ { "dropping-particle" : "", "family" : "Breen", "given" : "Fiona M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiol Behav", "id" : "ITEM-1", "issue" : "4-5", "issued" : { "date-parts" : [ [ "2006", "7", "30" ] ] }, "page" : "443-447", "title" : "Heritability of food preferences in young children.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Breen et al (2006)", "previouslyFormattedCitation" : "(Breen et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Breen et al (2006) found four categories, dessert foods, moderate for vegetables, moderate for fruits, and high liking for protein foods with heritability estimates of 0.20 (0.04 to 0.38), 0.37 (0.20 to 0.58), 0.51 (0.37 to 0.68), and 0.78 (0.63 to 0.92) respectively. In adult female twins from the United Kingdom (n=3262), five diet patterns, high fruit and vegetable, high alcohol, traditional English, dieting, and low meat accounted for 22% of the variance in dietary patterns with heritability estimates ranging from 0.41 to 0.48 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1375/twin.10.5.734", "ISSN" : "1832-4274", "PMID" : "17903115", "abstract" : "To examine the contribution of genetic factors to food choice, we determined dietary patterns from food frequency questionnaires in 3262 UK female twins aged 18 to 79 years. Five distinct dietary patterns were identified (fruit and vegetable, high alcohol, traditional English, dieting, low meat) that accounted for 22% of the total variance. These patterns are similar to those found in other singleton Western populations, and were related to body mass index, smoking status, physical activity and deprivation scores. Older subjects had higher scores on the fruit and vegetable and traditional English patterns, while lower social deprivation was associated with higher scores for fruit and vegetable, and lower scores for traditional English patterns. All 5 patterns were heritable, with estimates ranging from 41% to 48%. Among individual dietary components, a strongly heritable component was identified for garlic (46%), coffee (41%), fruit and vegetable sources (49%), and red meat (39%). Our results indicate that genetic factors have an important influence in determining food choice and dietary habits in Western populations. The relatively high heritability of specific dietary components implicates taste perception as a possible target for future genetic studies.", "author" : [ { "dropping-particle" : "", "family" : "Teucher", "given" : "Birgit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skinner", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skidmore", "given" : "Paula M L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cassidy", "given" : "Aedin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairweather-Tait", "given" : "Susan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hooper", "given" : "Lee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roe", "given" : "Mark a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foxall", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oyston", "given" : "Sarah L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cherkas", "given" : "Lynn F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perks", "given" : "Ursula C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Tim D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "MacGregor", "given" : "Alex J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2007", "10" ] ] }, "page" : "734-748", "title" : "Dietary patterns and heritability of food choice in a UK female twin cohort", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Teucher et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Teucher et al. 2007). In adult Finnish twin pairs (n=2009) factor analysis revealed four dietary patterns, healthy foods, high-fat foods, sweet foods, and meat with heritability estimates of 0.49 (0.40 to 0.56), 0.44 (0.34 to 0.53), 0.42 (0.32 to 0.51), and 0.39 (0.30 to 0.48) in males, and 0.54 (0.47 to 0.60), 0.47 (0.39 to 0.53), 0.43 (0.36 to 0.50), and 0.44 (0.36 to 0.51) in females respectively ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2007.08.025", "ISSN" : "0031-9384", "PMID" : "17897688", "abstract" : "The contribution of genetic factors to individual differences in food use was estimated in a large population-based twin cohort of young adults (22- to 27-year-old). Male and female twins (n=2009 complete twin pairs) evaluated use-frequencies of 24 food items using 5 categories (1=never-5=several times a day) in a postal questionnaire. Foods were categorized by factor analysis. Estimates of the relative proportions of additive genetic, shared environmental, and unshared environmental effects on the use-frequency of food items and factor scores were obtained by quantitative genetic modeling of twin data based on linear structural equations. Four factors of food use were identified: \"healthy\" foods, high-fat foods, sweet foods, and meats. The variance of the use-frequency of food items and food categories was explained by additive genetic and unshared environmental influences, whereas shared environmental factors did not contribute to food use. The average proportions of genetic effects on the total variance of the use-frequency of food items and food categories were 40% and 45%, respectively. Sex differences were observed in the magnitude of genetic influences for use-frequency of four food items (chocolate, other sweets, fried foods, and meat), and in genetic factors underlying the use of three (fresh vegetables, fruits, and cheeses) items. In conclusion, family environment does not appear to influence the food use of young adults and thus nutritional education should be targeted at this age group to support development of healthy eating patterns. In addition, the results illuminate the importance of the sex-specific genetic effects on food use.", "author" : [ { "dropping-particle" : "", "family" : "Keskitalo", "given" : "Kaisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silventoinen", "given" : "Karri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuorila", "given" : "Hely", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietil\u00e4inen", "given" : "Kirsi H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "Aila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiol Behav", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "1", "28" ] ] }, "page" : "235-242", "title" : "Genetic and environmental contributions to food use patterns of young adult twins", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keskitalo et al. 2008a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keskitalo et al. 2008a). Results from 4640 male and female twins in the United States aged 50 and over found two dietary patterns, items high in fat, salt, and sugar, and the other which was described as a healthy diet. The heritability estimate for the unhealthy diet pattern was 0.30 and 0.40 for the healthy diet pattern ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9165", "PMID" : "10500013", "abstract" : "BACKGROUND: Clinicians and researchers could benefit from a greater understanding of the role of genetic and environmental factors in human eating behavior. OBJECTIVE: Our aim was to estimate the relative influence of genetic and environmental factors on habitual eating patterns in middle-aged and elderly men and women. DESIGN: Male and female twins (n = 4640) aged >/=50 y completed a mailed version of the National Cancer Institute food-frequency questionnaire. Factor analysis was performed to identify eating patterns among respondents. Estimates of genetic, common environmental (shared by family members), and specific environmental (unique to an individual) influences were obtained for food use, serving size, and consumption frequency by comparing monozygotic and dizygotic twin-pair groups with structural equation analysis. RESULTS: Two independent eating patterns were identified: the first consisted of items high in fat, salt, and sugar, and the second reflected healthful eating habits. Although the influence of environmental factors was larger, between 15% and 38% of the total variation in pattern 1 and between 33% and 40% in pattern 2 were explained by genetic influences. Models accounting for sex differences in genetic and environmental estimates fit the data significantly better for food use and serving size of foods in eating pattern 1 and for food use in eating pattern 2. CONCLUSION: Although 60-85% of the variability in eating patterns was associated with environmental factors, genetic influences were also apparent and there was some evidence of sex specificity. These findings may be important in crafting dietary interventions and predicting adherence to these interventions.", "author" : [ { "dropping-particle" : "", "family" : "Bree", "given" : "M B", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eaves", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dwyer", "given" : "J T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1999", "10" ] ] }, "page" : "456-465", "title" : "Genetic and environmental influences on eating patterns of twins aged >/=50 y", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(van den Bree et al. 1999)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(van den Bree et al. 1999). The results from these studies indicate that in both children and adults, a moderate to high amount of the variance in food types consumed can be attributed to genetics. 2.2.3 Food consumption behavioursThe heritability of other food consumption behaviours thought to be associated with obesity have also been investigated. Neophobia, a fear of trying new foods, has been studied in children and adults. It is proposed that previously, neophobia motivated humans to eat familiar foods to avoid consuming new items which may not be safe. Between 20 and 30% of children are estimated to be neophobic with the trait being associated with decreased consumption of fruits, vegetables, and protein foods ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S000711450889246X", "ISBN" : "0007114508", "ISSN" : "0007-1145", "PMID" : "18257946", "abstract" : "Omnivores have the advantage of a variety of food options but face a challenge in identifying foods that are safe to eat. Not surprisingly, therefore, children show a relative aversion to new foods (neophobia) and a relative preference for familiar, bland, sweet foods. While this may in the past have promoted survival, in the modern food environment it could have an adverse effect on dietary quality. This review examines the evidence for genetic and environmental factors underlying individual differences in children's food preferences and neophobia. Twin studies indicate that neophobia is a strongly heritable characteristic, while specific food preferences show some genetic influence and are also influenced by the family environment. The advantage of the malleability of human food preferences is that dislike of a food can be reduced or even reversed by a combination of modelling and taste exposure. The need for effective guidance for parents who may be seeking to improve the range or nutritional value of foods accepted by their children is highlighted.", "author" : [ { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooke", "given" : "Lucy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brit J Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "3" ] ] }, "page" : "S15-21", "title" : "Genetic and environmental determinants of children's food preferences", "type" : "article-journal", "volume" : "99 Suppl 1" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wardle and Cooke 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wardle and Cooke 2008). In two independent twin studies conducted in pediatric populations using modeling techniques, heritability estimates of 0.72 and 0.78 were produced ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cooke", "given" : "Lucy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haworth", "given" : "Claire MA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "428-433", "title" : "Genetic and environmental influences on children's food neophobia", "type" : "article-journal", "volume" : "86" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/oby.20369", "ISSN" : "1930-739X", "PMID" : "23512929", "abstract" : "OBJECTIVE: The heritability of food neophobia, the tendency to avoid new foods, was tested in 4-7-year-old twins. We also examined whether food neophobia is associated with parent-child feeding relations or child body fat. DESIGN AND METHODS: 66 same-sex twin pairs, including 37 monozygotic (MZ) and 29 dizygotic (DZ) pairs were studied. Food neophobia was assessed by parent questionnaire (Child Food Neophobia Scale, CFNS), as were child-feeding practices and \"division of responsibility\" feeding relations. Child anthropometry and percent body fat were directly measured. RESULTS: MZ and DZ twin pair correlations for food neophobia were r = 0.71 and r = -0.01, respectively: heritability= 72%. Greater food neophobia was associated with reduced child eating compliance of prompted foods (P < 0.001) reduced eating compliance of initially refused foods (P < 0.001), and--among girls only--fewer parental food demands (P = 0.01). Interestingly, the correlation between maternal BMI and child BMI z-score was significant only for children high (P = 0.03), but not low (P = 0.55), in food neophobia. CONCLUSION: Child food neophobia, a highly heritable trait previously linked to emotionality, was associated with less compliant parent-child feeding relations. Strategies to combat food neophobia and foster more harmonious feeding relationships may have a role in obesity prevention.", "author" : [ { "dropping-particle" : "", "family" : "Faith", "given" : "Myles S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heo", "given" : "Moonseong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keller", "given" : "Kathleen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietrobelli", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "1650-1655", "title" : "Child food neophobia is heritable, associated with less compliant eating, and moderates familial resemblance for BMI", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cooke et al. 2007; Faith et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cooke et al. 2007; Faith et al. 2013). Similar estimates were found in young adults, 0.61 in females, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10519-010-9403-8", "ISSN" : "1573-3297", "PMID" : "20953688", "abstract" : "Food neophobia has been studied extensively in children, but its causal origins and relationship to eating behavior in adults are not well understood. We studied genetic and environmental effects on variation in food neophobia, measured using the Food Neophobia Scale, and explored associations between food neophobia and personality, pleasantness and use frequency of food groups, and body mass index in young adult twins (N = 1175, aged 20-25 years, 54.7% women). In women, additive genetic effects (heritability) accounted for 61% of variation in food neophobia, whereas in men, shared environmental effects explained 45% of the variation. Food neophobia negatively correlated with the personality trait Openness, corrected for the structural overlap (r = -0.23), and in women, these two traits had a genetic correlation (r (g) = -0.39). In addition, food neophobia negatively correlated with pleasantness and use frequency of fruits and vegetables and of fish and with mean pleasantness of foods. Once evolutionarily important, food neophobia should at present be considered in nutrition counseling as a possible barrier to a balanced diet.", "author" : [ { "dropping-particle" : "", "family" : "Knaapila", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silventoinen", "given" : "Karri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broms", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Richard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuorila", "given" : "Hely M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Behav Genet", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011", "7" ] ] }, "page" : "512-521", "title" : "Food neophobia in young adults: genetic architecture and relation to personality, pleasantness and use frequency of foods, and body mass index--a twin study", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Knaapila et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Knaapila et al. 2011) and in adult Finnish and British twins, 0.66 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2007.03.019", "ISSN" : "0031-9384", "PMID" : "17459432", "abstract" : "Food neophobia refers to reluctance to eat unfamiliar foods. We determined the heritability of food neophobia in a family and a twin sample. The family sample consisted of 28 Finnish families (105 females, 50 males, aged 18-78 years, mean age 49 years) and the twin sample of 468 British female twin pairs (211 monozygous and 257 dizygous pairs, aged 17-82 years, mean age 55 years). Food neophobia was measured using the ten-item Food Neophobia Scale (FNS) questionnaire, and its internationally validated six-item modification. The heritability estimate for food neophobia was 69 and 66% in Finnish families (h(2)) and 67 and 66% in British female twins (a(2)+d(2)) using the ten- and six-item versions of the FNS, respectively. The results from both populations suggest that about two thirds of variation in food neophobia is genetically determined.", "author" : [ { "dropping-particle" : "", "family" : "Knaapila", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuorila", "given" : "Hely", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silventoinen", "given" : "Karri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keskitalo", "given" : "Kaisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kallela", "given" : "Mikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wessman", "given" : "Maija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cherkas", "given" : "Lynn F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Tim D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiol Behav", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007", "8", "15" ] ] }, "page" : "573-578", "title" : "Food neophobia shows heritable variation in humans", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Knaapila et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Knaapila et al. 2007). Shared environment did not account for any of the variability in neophobia in any study except for males from the study by ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s10519-010-9403-8", "ISSN" : "1573-3297", "PMID" : "20953688", "abstract" : "Food neophobia has been studied extensively in children, but its causal origins and relationship to eating behavior in adults are not well understood. We studied genetic and environmental effects on variation in food neophobia, measured using the Food Neophobia Scale, and explored associations between food neophobia and personality, pleasantness and use frequency of food groups, and body mass index in young adult twins (N = 1175, aged 20-25 years, 54.7% women). In women, additive genetic effects (heritability) accounted for 61% of variation in food neophobia, whereas in men, shared environmental effects explained 45% of the variation. Food neophobia negatively correlated with the personality trait Openness, corrected for the structural overlap (r = -0.23), and in women, these two traits had a genetic correlation (r (g) = -0.39). In addition, food neophobia negatively correlated with pleasantness and use frequency of fruits and vegetables and of fish and with mean pleasantness of foods. Once evolutionarily important, food neophobia should at present be considered in nutrition counseling as a possible barrier to a balanced diet.", "author" : [ { "dropping-particle" : "", "family" : "Knaapila", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silventoinen", "given" : "Karri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broms", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Richard J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuorila", "given" : "Hely M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Behav Genet", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011", "7" ] ] }, "page" : "512-521", "title" : "Food neophobia in young adults: genetic architecture and relation to personality, pleasantness and use frequency of foods, and body mass index--a twin study", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Knaapila et al. (2011)", "previouslyFormattedCitation" : "(Knaapila et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Knaapila et al. (2011), in which shared environment was estimated to account for 45% of the variability. Studies have also found that in twin adolescents (n=254), the number of bites taken per minute is associated with BMI as well as hereditable with an estimate of 0.62 (0.45 to 0.74) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.2008.26175.1", "author" : [ { "dropping-particle" : "", "family" : "Llewellyn", "given" : "Clare H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Jaarsveld", "given" : "Cornelia H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boniface", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carnell", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1560-1566", "title" : "Eating rate is a heritable phenotype related to weight in children", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Llewellyn et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Llewellyn et al. 2008). In the Gemini Twin Study (n=4804) at three months of age, enjoyment of food, food responsiveness, slowness in eating, satiety responsiveness, and appetite size were all associated with weight with slowness in eating, satiety responsiveness, and appetite size having heritability estimates of 0.42 (0.26 to 0.54), 0.45 (0.32 to 0.56), and 0.41 (0.28 to 0.52) respectively ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.111.023671.Am", "author" : [ { "dropping-particle" : "", "family" : "Llewellyn", "given" : "Clare H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Jaarsveld", "given" : "Cornelia H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Abigail", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Inherited behavioral susceptibility to adiposity in infancy : a multivariate genetic analysis of appetite and weight in the Gemini birth cohort 1 \u2013 3", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Llewellyn et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Llewellyn et al. 2012). The Gemini Study had previously looked at the same population prior to three months of age and found higher heritability estimates for slowness in eating, satiety responsiveness, and appetite size ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.2009.28868.INTRODUCTION", "author" : [ { "dropping-particle" : "", "family" : "Llewellyn", "given" : "Clare H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Jaarsveld", "given" : "Cornelia H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carnell", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1172-1179", "title" : "Nature and nurture in infant appetite : analysis of the Gemini twin birth cohort", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Llewellyn et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Llewellyn et al. 2010) indicating that the relative influence of genetics on these phenotypes may change over time. In older children, satiety responsiveness has been estimated to have a heritability of 0.63 (0.39 to 0.81) and 0.75 (0.52 to 0.85) for food cue responsiveness ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2008.127", "ISSN" : "1476-5497", "PMID" : "18679413", "abstract" : "The modern environment is ubiquitously 'obesogenic', yet people vary enormously in weight. One factor contributing to weight variation could be genetically determined differences in appetite that modulate susceptibility to the environment. We assessed the relative contribution of genes and environment for two aspects of appetite that have been implicated in obesity.", "author" : [ { "dropping-particle" : "", "family" : "Carnell", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haworth", "given" : "C M a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Eat Disord", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "1468-1473", "title" : "Genetic influence on appetite in children", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Carnell et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Carnell et al. 2008), and 0.51 (+/- 0.10) for eating in the absence of hunger ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2007.177", "ISSN" : "1930-7381", "PMID" : "17557986", "abstract" : "OBJECTIVE: Eating in the absence of hunger (EAH) may be a genetically influenced phenotype of overweight children, but evidence is limited. This research evaluated the heritability (h(2)) of EAH and its association with overweight among Hispanic children 5 to 18 years old. Genetic and environmental associations of EAH with overweight, fat mass, and key hormonal regulators of food intake were also evaluated. RESEARCH METHODS AND PROCEDURES: A family design was used to study 801 children from 300 Hispanic families. Weighed food intakes were used to measure EAH after an ad libitum dinner providing 50% of estimated energy needs. Fasting ghrelin, amylin, insulin, and leptin were measured by immunoassays. Measured heights, weights, and fat mass (using DXA) were obtained. Total energy expenditure (TEE) was measured by room respiration calorimetry. RESULTS: On average, children consumed 41% of TEE at the dinner meal, followed by an additional 19% of TEE in the absence of hunger. Overweight children consumed 6.5% more energy at dinner (p < 0.001) and 14% more energy in the absence of hunger (p < 0.001) than non-overweight children. Significant heritabilities were seen for EAH (h(2) = 0.51) and dinner intake (h(2) = 0.52) and for fasting levels of ghrelin (h(2) = 0.67), amylin (h(2) = 0.37), insulin (h(2) = 0.37), and leptin (h(2) = 0.34). Genetic correlations were seen between eating behavior and fasting hormones, suggesting common underlying genes affecting their expression. DISCUSSION: This research provides new evidence that overweight Hispanic children exhibit elevated levels of hyperphagic eating behaviors that are influenced by genetic endowment.", "author" : [ { "dropping-particle" : "", "family" : "Fisher", "given" : "Jennifer O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Guowen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaramillo", "given" : "Sandra J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cole", "given" : "Shelly a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Comuzzie", "given" : "Anthony G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butte", "given" : "Nancy F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2007", "6" ] ] }, "page" : "1484-1495", "title" : "Heritability of hyperphagic eating behavior and appetite-related hormones among Hispanic children", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fisher et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fisher et al. 2007).In adult populations, the Three Factor Eating Questionnaire has been used to determine the heritability of cognitive restraint, uncontrolled eating, and emotional eating. In male and female Finnish and British twins, heritability estimates were 0.26 to 0.63 for cognitive restraint, 0.45 to 0.69 for uncontrolled eating, and 0.09 to 0.45 for emotional eating when divided by sex and ethnicity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1938-3207", "PMID" : "18689360", "abstract" : "BACKGROUND: The relation between body weight and energy-dense foods remains unclear. OBJECTIVE: We estimated the effects of genetic and environmental factors on cognitive and emotional aspects of dieting behavior, body mass index (BMI), and responses to fatty foods and on their relations. DESIGN: A total of 1326 adult twin persons (aged 17-82 y; 17% M and 83% F) from the United Kingdom and Finland completed the revised version of the Three-Factor Eating Questionnaire (TFEQ-R18) and reported the liking and use-frequency of 4 sweet-and-fatty and salty-and-fatty food items (6 items in the United Kingdom and 5 items in Finland). Genetic modeling was done by using linear structural equations. RESULTS: Heritability estimates were calculated separately for the countries and sexes; they were 26-63% for cognitive restraint, 45-69% for uncontrolled eating, and 9-45% for emotional eating, respectively. Of the variation in liking and use-frequency of fatty foods, 24-54% was attributed to interindividual genetic differences. No significant correlations were observed between BMI and fatty food use or liking. However, BMI was positively (mostly genetically) correlated (genetic r = 0.16-0.51) with all of the dieting behaviors, and they correlated with fatty food use and liking ratings. Uncontrolled eating was both genetically and environmentally associated with liking for salty-and-fatty foods (genetic and environmental r = 0.16), and emotional eating was genetically associated with liking for sweet-and-fatty foods (genetic r = 0.31). CONCLUSIONS: The relation between BMI and diet appears to be mediated through dieting behaviors. Dietary counseling should focus on unhealthy dieting behaviors rather than only on direct advice on food use.", "author" : [ { "dropping-particle" : "", "family" : "Keskitalo", "given" : "Kaisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuorila", "given" : "Hely", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Tim D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cherkas", "given" : "Lynn F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knaapila", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silventoinen", "given" : "Karri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "263-271", "title" : "The Three-Factor Eating Questionnaire, body mass index, and responses to sweet and salty fatty foods: a twin study of genetic and environmental associations", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keskitalo et al. 2008b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keskitalo et al. 2008b). In another study of adult twins (n=110), the same questionnaire provided heritability estimates of 0.44 for cognitive restraint, 0.24 for perceived hunger, and 0.58 for restraint score scales ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.nut.2004.07.010", "ISSN" : "0899-9007", "PMID" : "15811764", "abstract" : "OBJECTIVE: Dietary restraint, disinhibition, and perceived hunger have been shown to affect food intake and body weight and are thought to be risk factors for eating disorders, but little is known about their origins. We investigated the influence of heredity, shared (familial) environment, and individual environment on dietary restraint disinhibition, perceived hunger and their relation to body size and food intake. METHODS: Scores on the Three Factor Eating Questionnaire and the Restraint Scale in addition to height, weight, body mass index, and 7-d diary reported nutrient intakes were obtained from 39 identical, 60 fraternal same-sex, and 50 fraternal opposite-sex adult twin pairs who were living independently. Linear structural modeling was applied to investigate the nature and degree of genetic and environmental influences. RESULTS: Analysis showed significant genetic and individual environmental, but not shared (familial) environmental, influences on cognitive restraint, perceived hunger, and Restraint Scale scores, with genes accounting for 44%, 24%, and 58% of the variance, respectively. In contrast, disinhibition was found to be significantly influenced by the shared (familial) environment, accounting for 40% of the variance. Further analysis showed that cognitive restraint and perceived hunger heritabilities could not be accounted for by significant heritabilities of body weight, height, or body mass index. In contrast, the heritability of Restraint Scale scores was found to be related to body size. Cognitive restraint was negatively correlated with nutrient intake, and differences in cognitive restraint were found to be related to differences in the body sizes of identical twin pairs. CONCLUSIONS: Dietary restraint appears to be another component in a package of genetically determined physiologic, sociocultural, and psychological processes that regulate energy balance, whereas dietary disinhibition may be the intermediary between upbringing and the development of overweight and/or eating disorders.", "author" : [ { "dropping-particle" : "", "family" : "Castro", "given" : "John M", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lilenfeld", "given" : "Lisa R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nutr", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2005", "4" ] ] }, "page" : "446-55", "title" : "Influence of heredity on dietary restraint, disinhibition, and perceived hunger in humans", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(de Castro and Lilenfeld 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(de Castro and Lilenfeld 2005). A Swedish twin study (n=782 pairs) found heritability estimates of 0.59 (0.52 to 0.66) for cognitive restraint, 0.60 (0.52 to 0.66) for emotional eating and 0.45 (0.36 to 0.53) for uncontrolled eating ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9165", "PMID" : "15755823", "abstract" : "BACKGROUND: Eating behavior may be implicated in the increasing prevalence of overweight and obesity, presumably in relation to easy access to energy-dense and highly palatable foods. OBJECTIVE: The aim of the present study was to disentangle genetic and environmental influences on eating behavior in a population-based cohort of male twins. DESIGN: The study included 326 dizygotic and 456 monozygotic male twin pairs aged 23-29 y from Sweden. The revised 21-item version of the Three-Factor Eating Questionnaire (TFEQ-R21) was used to assess eating behavior. This validated instrument consists of 3 dimensions: cognitive restraint, emotional eating, and uncontrolled eating. Structural equation modeling was used to estimate the heritability of eating behavior. RESULTS: Cognitive restraint was the only TFEQ-R21 scale that significantly correlated with BMI (r = 0.39, P < 0.0001). The best-fitted models gave a heritability of 59% (95% CI: 52%, 66%) for cognitive restraint, 60% (95% CI: 52%, 67%) for emotional eating, and 45% (95% CI: 36%, 53%) for uncontrolled eating. CONCLUSIONS: These results show the great importance of genetic factors in the eating behavior of a large, unselected population of young adult male twins. Nonshared environmental factors were also important, whereas shared environmental factors did not contribute to eating behavior.", "author" : [ { "dropping-particle" : "", "family" : "Tholin", "given" : "Sanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasmussen", "given" : "Finn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tynelius", "given" : "Per", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karlsson", "given" : "Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005", "3" ] ] }, "page" : "564-569", "title" : "Genetic and environmental influences on eating behavior: the Swedish Young Male Twins Study", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Tholin et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Tholin et al. 2005). Number of meals consumed per day is also hereditable with an estimate of 0.44 in adult twin pairs ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0031-9384", "PMID" : "8511185", "abstract" : "The heritability of nutrient intake was investigated with 109 identical and 86 fraternal adult twin pairs who were paid to maintain 7-day food intake diaries. Both classical analysis of heritability and linear structural modeling revealed significant additive genetic influences on body size, height and weight, and body fatness (body-mass index). Significant heritabilities were also found for the amount of food energy ingested daily, as well as its macronutrient, alcohol, and water content. Linear structural modeling analysis showed that 65% of the variance in energy intake was attributable to heredity. In addition, the pattern of intake, meal frequency, size, and meal macronutrient, alcohol, and water composition, were also found to have strong heritabilities. Linear structural modeling indicated that 44% of the variance in meal frequency and 65% of the variance in meal size was attributable to heredity. However, shared, familial environment had no significant impact on the levels or pattern of intake in adulthood. These results indicate that not only body size but also the pattern and amounts of nutrients ingested by humans in natural environments are strongly influenced by the immediate environment and heredity, but not at all by the familial environment.", "author" : [ { "dropping-particle" : "", "family" : "Castro", "given" : "J M", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiol Behav", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1993", "4" ] ] }, "page" : "7777-82", "title" : "Genetic influences on daily intake and meal patterns of humans", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(de Castro 1993)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(de Castro 1993). Despite the variation in heritability estimates which could be due to sampling effects, different ethnicities, differences in measuring phenotypes, the effect of age, and different statistical methods, there is strong evidence that food consumption behaviour is at least moderately hereditable. 2.2.4 Conclusions In both children and adults there is a growing body of evidence that a higher intake of calories, the total amount and relative intake of macronutrients including protein, fat, and carbohydrates, food consumption patterns such as eating more high fat foods, more fruits and vegetables, or high protein diets, as well as eating behaviours are moderately to highly heritable traits. At this point in time, not enough studies have been conducted to determine if heritability changes across the lifespan, what the effect of sex is, and how it might change between cultures and ethnicities. Interestingly, most of the studies concluded that the shared environment element (C), did not significantly contribute to the variation in phenotype with the individual environment playing a much larger role. 2.3 Current state of knowledge of the genetics of obesity 2.3.1 Monogenic obesityTo date, the investigation of monogenic forms of obesity have provided the majority of the information regarding the genetics of obesity. Monogenic forms of obesity include both syndromic obesity which is associated with specific clinical phenotypes in addition to obesity, often including mild to severe cognitive deficits and unusual behaviour ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/pbc.23372.An", "author" : [ { "dropping-particle" : "", "family" : "Chung", "given" : "Wendy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatr Blood Cancer", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "122-128", "title" : "An overview of monogenic and syndromic obesities in humans", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Chung 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Chung 2012) as well as non-syndromic obesity which is characterized by early-onset, severe obesity with extreme hyperphagia resulting from a single gene disorder ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677921", "ISSN" : "1875-5488", "PMID" : "22043164", "abstract" : "Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of \"deep phenotyping\" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "154-168", "title" : "Molecular basis of obesity: current status and future prospects.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011b). There are over 30 types of syndromic obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/gm157", "ISSN" : "1756-994X", "PMID" : "20587078", "abstract" : "The biological causes of childhood obesity are complex. Environmental factors, such as massive marketing campaigns for food leading to over-nutrition and snacking and the decline in physical activity, have undoubtedly contributed to the increased prevalence of overweight and obesity in children, but these cannot be considered as the only causes. Susceptibility to obesity is also determined to a great extent by genetic factors. Furthermore, molecular mechanisms involved in the regulation of gene expression, such as epigenetic mechanisms, can increase the risk of developing early-onset obesity. There is evidence that early-onset obesity is a heritable disorder, and a range of genetic factors have recently been shown to cause monogenic, syndromic and polygenic forms of obesity, in some cases interacting with environmental exposures. Modifications of the transcriptome can lead to increased adiposity, and the gut microbiome has recently been shown to be key to the genesis of obesity. These new genomic discoveries complement previous knowledge on the development of early-onset obesity and provide new perspectives for research on the complex molecular and physiological mechanisms involved in this disease. Personalized preventive strategies and genomic medicine may become possible in the near future.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genome Medicine", "id" : "ITEM-1", "issue" : "36", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "title" : "Genomic insights into early-onset obesity", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2010), however the mechanisms through which the genetic mutations effect energy homeostasis are not understood in all cases ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/pbc.23372.An", "author" : [ { "dropping-particle" : "", "family" : "Chung", "given" : "Wendy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatr Blood Cancer", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "122-128", "title" : "An overview of monogenic and syndromic obesities in humans", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Chung 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Chung 2012). Prader Willi syndrome is the most common form of syndromic obesity affecting 1 in 15 000 to 20 000 live births and involves a loss of expression of paternal genes in the 15q11-13 region. Other well-known forms of syndromic obesity include Bardet-Biedl syndrome, Alstrom syndrome, and WAGR syndrome ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/pbc.23372.An", "author" : [ { "dropping-particle" : "", "family" : "Chung", "given" : "Wendy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatr Blood Cancer", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "122-128", "title" : "An overview of monogenic and syndromic obesities in humans", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Chung 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Chung 2012). Though the precise mechanisms of action may not be known, all forms of monogenic obesity involve the central nervous system (CNS) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/gm157", "ISSN" : "1756-994X", "PMID" : "20587078", "abstract" : "The biological causes of childhood obesity are complex. Environmental factors, such as massive marketing campaigns for food leading to over-nutrition and snacking and the decline in physical activity, have undoubtedly contributed to the increased prevalence of overweight and obesity in children, but these cannot be considered as the only causes. Susceptibility to obesity is also determined to a great extent by genetic factors. Furthermore, molecular mechanisms involved in the regulation of gene expression, such as epigenetic mechanisms, can increase the risk of developing early-onset obesity. There is evidence that early-onset obesity is a heritable disorder, and a range of genetic factors have recently been shown to cause monogenic, syndromic and polygenic forms of obesity, in some cases interacting with environmental exposures. Modifications of the transcriptome can lead to increased adiposity, and the gut microbiome has recently been shown to be key to the genesis of obesity. These new genomic discoveries complement previous knowledge on the development of early-onset obesity and provide new perspectives for research on the complex molecular and physiological mechanisms involved in this disease. Personalized preventive strategies and genomic medicine may become possible in the near future.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genome Medicine", "id" : "ITEM-1", "issue" : "36", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "title" : "Genomic insights into early-onset obesity", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2010). Specifically, monogenic forms of obesity involve genes that impact the neuronal differentiation of the periventricular nucleus (PVN) and the leptin/melanocortin pathway. Eleven genes leading to monogenic obesity have been discovered including SH2B1 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1172/JCI62696.4732", "author" : [ { "dropping-particle" : "", "family" : "Doche", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochukova", "given" : "Elena G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Su", "given" : "Hsiao-wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearce", "given" : "Laura R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keogh", "given" : "Julia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henning", "given" : "Elana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cline", "given" : "Joel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dale", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheetham", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Argetsinger", "given" : "Lawrence S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rahilly", "given" : "Stephen O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rui", "given" : "Liangyou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carter-su", "given" : "Christin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Invest", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "4732-4736", "title" : "Human SH2B1 mutations are associated with maladaptive behaviors and obesity", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Doche et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Doche et al. 2012), LEP, LEPR, POMC, PCSK1, MC4R, MC3R ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/hmg/ddq472", "ISSN" : "1460-2083", "PMID" : "21047972", "abstract" : "In contrast to the melanocortin 4 receptor, the possible role of the melanocortin 3 receptor (MC3R) in regulating body weight is still debated. We have previously reported three mutations in the MC3R gene showing association with human obesity, but these results were not confirmed in a study of severe obese North American adults. In this study, we evaluated the entire coding region of MC3R in 839 severely obese subjects and 967 lean controls of Italian and French origin. In vitro functional analysis of the mutations detected was also performed. The total prevalence of rare MC3R variants was not significantly different in obese subjects when compared with controls (P= 0.18). However, the prevalence of mutations with functional alterations was significantly higher in the obese group (P= 0.022). In conclusions, the results of this large study demonstrate that in the populations studied functionally significant MC3R variants are associated with obesity supporting the current hypothesis that rare variants might have a stronger impact on the individual susceptibility to gain weight. They also underline the importance of detailed in vitro functional studies in order to prove the pathogenic effect of such variants. Further investigations in larger cohorts will be needed in order to define the specific phenotypic characteristics potentially correlated with reduced MC3R signalling.", "author" : [ { "dropping-particle" : "", "family" : "Mencarelli", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubern", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alili", "given" : "Rohia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maestrini", "given" : "Sabrina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benajiba", "given" : "Lina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tagliaferri", "given" : "Mariantonella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rinaldi", "given" : "Maura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simon", "given" : "Chantal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tounian", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liuzzi", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blasio", "given" : "Anna Maria", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clement", "given" : "Karine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hum Mol Genet", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011", "1", "15" ] ] }, "page" : "392-399", "title" : "Rare melanocortin-3 receptor mutations with in vitro functional consequences are associated with human obesity", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mencarelli et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mencarelli et al. 2011), MRAP2 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1126/science.1233000", "ISSN" : "1095-9203", "PMID" : "23869016", "abstract" : "Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro. To investigate the physiological role of brain-expressed melanocortin 2 receptor accessory protein 2 (MRAP2), we characterized mice with whole-body and brain-specific targeted deletion of Mrap2, both of which develop severe obesity at a young age. Mrap2 interacts directly with melanocortin 4 receptor (Mc4r), a protein previously implicated in mammalian obesity, and it enhances Mc4r-mediated generation of the second messenger cyclic adenosine monophosphate, suggesting that alterations in Mc4r signaling may be one mechanism underlying the association between Mrap2 disruption and obesity. In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans.", "author" : [ { "dropping-particle" : "", "family" : "Asai", "given" : "Masato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramachandrappa", "given" : "Shwetha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joachim", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nuthalapati", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramanathan", "given" : "Visali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strochlic", "given" : "David E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferket", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linhart", "given" : "Kirsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Novoselova", "given" : "Tatiana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garg", "given" : "Sumedha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ridderstr\u00e5le", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keogh", "given" : "Julia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chan", "given" : "Li F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clark", "given" : "Adrian J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Majzoub", "given" : "Joseph a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Science", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "7", "19" ] ] }, "page" : "275-278", "title" : "Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity", "type" : "article-journal", "volume" : "341" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Asai et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Asai et al. 2013), SIM1, BDNF and its receptor TrkB coded by the NTRK2 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677921", "ISSN" : "1875-5488", "PMID" : "22043164", "abstract" : "Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of \"deep phenotyping\" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "154-168", "title" : "Molecular basis of obesity: current status and future prospects.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011b). See Table 1 for information about proteins coded by the obesity predisposing SNPs. The leptin/melanocortin pathway plays a critical role in food consumption regulation (Figure 1). Leptin is a cytokine like hormone secreted by adipocytes that acts in the hypothalamus to regulate food intake, energy expenditure, and nutrient portioning. Individuals unable to produce leptin or who have leptin resistance due to faulty receptors experience hyperphagia and consequent obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/pbc.23372.An", "author" : [ { "dropping-particle" : "", "family" : "Chung", "given" : "Wendy K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatr Blood Cancer", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "122-128", "title" : "An overview of monogenic and syndromic obesities in humans", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Chung 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Chung 2012). The exact prevalence of monogenic obesity is unknown as a random cohort of obese subjects has not yet been genotyped, however it is estimated to be between 5 and 10% of all obese individuals for the eleven currently known genes and the 16p11.2 deletion ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677895", "ISSN" : "1875-5488", "PMID" : "22043165", "abstract" : "Candidate gene and genome-wide association studies have led to the discovery of nine loci involved in Mendelian forms of obesity and 58 loci contributing to polygenic obesity. These loci explain a small fraction of the heritability for obesity and many genes remain to be discovered. However, efforts in obesity gene identification greatly modified our understanding of this disorder. In this review, we propose an overlook of major lessons learned from 15 years of research in the field of genetics and obesity. We comment on the existence of the genetic continuum between monogenic and polygenic forms of obesity that pinpoints the role of genes involved in the central regulation of food intake and genetic predisposition to obesity. We explain how the identification of novel obesity predisposing genes has clarified unsuspected biological pathways involved in the control of energy balance that have helped to understand past human history and to explore causality in epidemiology. We provide evidence that obesity predisposing genes interact with the environment and influence the response to treatment relevant to disease prediction.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "169-179", "title" : "Genetics of obesity: What have we Learned?", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011a).right2684780Table 1. Gene Symbols and Proteins Coded00Table 1. Gene Symbols and Proteins CodedGene SymbolProtein CodedSH2B1SH2B adaptor protein 1LEPLeptinLEPRLeptin receptorPOMCProopiomelanocortin prohormone convertase 1PCSK1Proprotein convertase 1/3MC4RMelanocortin 4 receptorMC3RMelanocortin 3 receptorMRAP2Melanocortin 2 receptor accessory protein 2SIM1Single-minded homolog 1BDNFBrain derived neurotrophic factorNTRK2Nueurotrophic tyrosine kinase receptor type 2 – codes TRkB receptorFigure 1. The role of monogenic obesity genes in the melanocortin pathway. White adipose tissue releases leptin in response to increased adipose tissue ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1172/JCI62696.4732", "author" : [ { "dropping-particle" : "", "family" : "Doche", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochukova", "given" : "Elena G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Su", "given" : "Hsiao-wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearce", "given" : "Laura R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keogh", "given" : "Julia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henning", "given" : "Elana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cline", "given" : "Joel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dale", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheetham", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Argetsinger", "given" : "Lawrence S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rahilly", "given" : "Stephen O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rui", "given" : "Liangyou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carter-su", "given" : "Christin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Invest", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "4732-4736", "title" : "Human SH2B1 mutations are associated with maladaptive behaviors and obesity", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Doche et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Doche et al. 2012). Leptin travels to the brain, specifically the hypothalamus located in the periventricular nucleus. There it binds to leptin receptors on POMC neurons and AgRP neurons ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/iub.1187.Control", "author" : [ { "dropping-particle" : "", "family" : "Carmo", "given" : "Jussara M", "non-dropping-particle" : "do", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "Alexandre A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubinion", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sessums", "given" : "Price O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sabira", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Zhen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "John E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "IUBMB Life", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "201-207", "title" : "Control of metabolic and cardiovascular function by the leptin-brain melanocortin pathway", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(do Carmo et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(do Carmo et al. 2013). SH2B1 plays a role in the leptin response by modulating the ability of leptin to bind to leptin receptors ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1172/JCI62696.4732", "author" : [ { "dropping-particle" : "", "family" : "Doche", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochukova", "given" : "Elena G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Su", "given" : "Hsiao-wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pearce", "given" : "Laura R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keogh", "given" : "Julia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henning", "given" : "Elana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cline", "given" : "Joel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dale", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheetham", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Argetsinger", "given" : "Lawrence S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rahilly", "given" : "Stephen O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rui", "given" : "Liangyou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carter-su", "given" : "Christin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Invest", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "4732-4736", "title" : "Human SH2B1 mutations are associated with maladaptive behaviors and obesity", "type" : "article-journal", "volume" : "122" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Doche et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Doche et al. 2012). On the POMC neurons, leptin binding causes the synthesis of which is then cleaved by PC 1/3 to produce α-MSH ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2007-0687", "ISSN" : "0021-972X", "PMID" : "17595246", "abstract" : "CONTEXT: Congenital deficiency of the neuroendocrine-specific enzyme prohormone convertase (PC) 1/3 leads to a syndrome characterized by obesity, small intestinal dysfunction, and dysregulation of glucose homeostasis in humans. To date, only two unrelated subjects with this disorder have been reported. Research DESIGN AND METHODS: We now report a third proband, a 6-yr-old boy, offspring of a consanguineous union of parents of North African origin, who was homozygous for a novel missense mutation Ser307Leu. We characterized the functional properties of the mutant PC1/3 and characterized the clinical phenotype of the patient. RESULTS: In vitro this mutation markedly impairs the catalytic activity of the convertase. However, in contrast to other previously described naturally occurring mutations, intracellular trafficking of this mutant enzyme appeared normal. The Ser307Leu mutant retained some autocatalytic activity, even though it was completely inactive on other substrates. As with the previous two patients, this child had obesity and persistent diarrhea, however, there was no history of reactive hypoglycemia. The patient showed markedly increased food intake at an ad libitum test meal, confirming that hyperphagia makes a major contribution to the obesity seen in this syndrome. CONCLUSION: This case extends the clinical and molecular spectrum of human congenital PC1/3 deficiency.", "author" : [ { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Volders", "given" : "Karolien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stanhope", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heuschkel", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lank", "given" : "Emma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keogh", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Creemers", "given" : "John W M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "3369-3373", "title" : "Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3", "type" : "article-journal", "volume" : "92" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s12272-013-0020-y", "ISSN" : "0253-6269", "PMID" : "23359004", "abstract" : "The rapidly increasing prevalence of obesity confers a huge health burden globally. The hypothalamus plays a central role in the regulation of energy homeostasis by integrating multiple metabolic signals from peripheral organs and modulating feeding behavior and energy metabolism. Leptin, a key appetite-regulating hormone derived from the white adipose tissue, primarily acts on hypothalamic neurons to activate catabolic pathway and inhibit anabolic pathway, which can result in anorexia and weight reduction. Despite striking obesity resulting from leptin deficiency, treatment with this hormone in human obesity has been unsuccessful due to leptin resistance. In this review, we describe recent researches extending our understanding of obesity-associated hypothalamic leptin resistance.", "author" : [ { "dropping-particle" : "", "family" : "Jung", "given" : "Chang Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Min-Seon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Pharmacal Research", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "201-207", "title" : "Molecular mechanisms of central leptin resistance in obesity", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Farooqi et al. 2007; Jung and Kim 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Farooqi et al. 2007; Jung and Kim 2013). On AgPR neurons, leptin binding decreases the neuronal activity of NPY and AgRP. AgRP and α-MSH compete for binding on MC3R and MC4R ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12272-013-0020-y", "ISSN" : "0253-6269", "PMID" : "23359004", "abstract" : "The rapidly increasing prevalence of obesity confers a huge health burden globally. The hypothalamus plays a central role in the regulation of energy homeostasis by integrating multiple metabolic signals from peripheral organs and modulating feeding behavior and energy metabolism. Leptin, a key appetite-regulating hormone derived from the white adipose tissue, primarily acts on hypothalamic neurons to activate catabolic pathway and inhibit anabolic pathway, which can result in anorexia and weight reduction. Despite striking obesity resulting from leptin deficiency, treatment with this hormone in human obesity has been unsuccessful due to leptin resistance. In this review, we describe recent researches extending our understanding of obesity-associated hypothalamic leptin resistance.", "author" : [ { "dropping-particle" : "", "family" : "Jung", "given" : "Chang Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Min-Seon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Pharmacal Research", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "201-207", "title" : "Molecular mechanisms of central leptin resistance in obesity", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Jung and Kim 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Jung and Kim 2013). If α-MSH binds to MC3R and MC4R, the activity of the protein is increased causing a suppression of appetite. If AgRP binds the activity of MC3R and MC4R are reduced and appetite is increased ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12272-013-0020-y", "ISSN" : "0253-6269", "PMID" : "23359004", "abstract" : "The rapidly increasing prevalence of obesity confers a huge health burden globally. The hypothalamus plays a central role in the regulation of energy homeostasis by integrating multiple metabolic signals from peripheral organs and modulating feeding behavior and energy metabolism. Leptin, a key appetite-regulating hormone derived from the white adipose tissue, primarily acts on hypothalamic neurons to activate catabolic pathway and inhibit anabolic pathway, which can result in anorexia and weight reduction. Despite striking obesity resulting from leptin deficiency, treatment with this hormone in human obesity has been unsuccessful due to leptin resistance. In this review, we describe recent researches extending our understanding of obesity-associated hypothalamic leptin resistance.", "author" : [ { "dropping-particle" : "", "family" : "Jung", "given" : "Chang Hee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Min-Seon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Pharmacal Research", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "201-207", "title" : "Molecular mechanisms of central leptin resistance in obesity", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Jung and Kim 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Jung and Kim 2013). MRAP2 is an accessory protein that causes a small but significant reduction in the surface expression of MC4R and in combination with MRAP also reduces the function of MC3R ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1073/pnas.0809918106", "ISSN" : "1091-6490", "PMID" : "19329486", "abstract" : "The melanocortin receptor (MCR) family consists of 5 G protein-coupled receptors (MC1R-MC5R) with diverse physiologic roles. MC2R is a critical component of the hypothalamic-pituitary-adrenal axis, whereas MC3R and MC4R have an essential role in energy homeostasis. Mutations in MC4R are the single most common cause of monogenic obesity. Investigating the way in which these receptors signal and traffic to the cell membrane is vital in understanding disease processes related to MCR dysfunction. MRAP is an MC2R accessory protein, responsible for adrenal MC2R trafficking and function. Here we identify MRAP2 as a unique homologue of MRAP, expressed in brain and the adrenal gland. We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). Collectively, our data identify MRAP and MRAP2 as unique bidirectional regulators of the MCR family.", "author" : [ { "dropping-particle" : "", "family" : "Chan", "given" : "Li F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Webb", "given" : "Tom R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chung", "given" : "Teng-Teng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meimaridou", "given" : "Eirini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooray", "given" : "Sadani N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guasti", "given" : "Leonardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chapple", "given" : "J Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Egertov\u00e1", "given" : "Michaela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elphick", "given" : "Maurice R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheetham", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metherell", "given" : "Louise a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clark", "given" : "Adrian J L", "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" : "15", "issued" : { "date-parts" : [ [ "2009", "4", "14" ] ] }, "page" : "6146-6151", "title" : "MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family", "type" : "article-journal", "volume" : "106" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Chan et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Chan et al. 2009). Similarly, a deficiency in SIM1 causes a lower concentration of MC4R mRNA in the periventricular nucleus ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2013.188", "ISSN" : "1476-5497", "PMID" : "24097297", "abstract" : "Background:The transcription factor SIM1 (Single-minded 1) is involved in the control of food intake and in the pathogenesis of obesity. In mice, Sim1 is involved in the development of the paraventricular nucleus, and Sim1 deficiency leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in the SIM1 gene region have been reported in obese individuals. Furthermore, recent data also suggest that loss-of-function point mutations in SIM1 are responsible for SIM1 haplo-insufficiency that is involved in causing human obesity. In this study, we therefore wanted to expand the evidence regarding the involvement of SIM1 mutations in the pathogenesis of severe early-onset obesity.Methods:We screened 561 severely overweight and obese children and adolescents and 453 lean adults for mutations in the coding region of the SIM1 gene. Mutation screening in all patients and lean individuals was performed by high-resolution melting curve analysis combined with direct sequencing. To evaluate the effect of the mutations on SIM1 transcriptional activity, luciferase reporter assays were performed.Results:Mutation analysis identified four novel nonsynonymous coding variants in SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E. Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also identified. Screening of the lean control population revealed the occurrence of four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For variants p.T481K and p.A517V, which were found in obese individuals, a decrease in SIM1 transcriptional activity was observed, whereas the transcriptional activity of all variants found in lean individuals resembled wild type.Conclusions:In this study, we have demonstrated the presence of rare SIM1 variants in both an obese pediatric population and a population of lean adult controls. Further, we have shown that functional in vitro analysis of SIM1 variants may help in distinguishing benign variants of no pathogenic significance from variants which contribute to the obesity phenotype.", "author" : [ { "dropping-particle" : "", "family" : "Zegers", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beckers", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hendrickx", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camp", "given" : "J K", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Craemer", "given" : "V", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verrijken", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoorenbeeck", "given" : "K", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verhulst", "given" : "S L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rooman", "given" : "R P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desager", "given" : "K N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Massa", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaal", "given" : "L F", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hul", "given" : "W", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2014", "7" ] ] }, "page" : "1000-1004", "publisher" : "Nature Publishing Group", "title" : "Mutation screen of the SIM1 gene in pediatric patients with early-onset obesity", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Zegers et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Zegers et al. 2014). Though the precise mechanisms are unknown BDNF and its receptor TRkB play a role in moderating the effect of the melanocortin pathway downstream ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/en.2008-1184", "ISSN" : "1945-7170", "PMID" : "19179431", "abstract" : "It has been shown that the neurotropin brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin-related kinase receptor type B (TrkB), contribute to the central control of food intake. BDNF has previously been implicated as a probable downstream effector of melanocortinergic signaling within the ventromedial hypothalamus, and we have shown its implication as an anorexigenic factor within the brainstem autonomic integrator of food intake control, namely the dorsal vagal complex (DVC). In the brainstem, the melanocortinergic signaling pathway is known to integrate phasic responses to satiety signals, such as cholecystokinin. In this study, we explored the interactions between melanocortin and BDNF/TrkB signaling within the DVC. First, we tested the effect of a local pharmacological activation or inhibition of melanocortin receptors type 3/4 (MC3/4R) on BDNF protein content in the DVC of adult rats. We showed that fourth intracerebroventricular delivery of MC3/4R agonist and antagonist increased and decreased the BDNF protein content within the DVC, respectively. Second, we showed that the orexigenic effect of a selective MC4R antagonist delivered fourth-icv can be blocked by a coadministration of BDNF. We also tested the causal role of BDNF/TrkB signaling in the anorexigenic effect of melanocortinergic signaling by using a recently developed analog-sensitive kinase allele murine model (TrkB(F616A) mice) and showed that the pharmacological blockade of TrkB abolished the anorexigenic effect of a selective MC4R agonist and of cholecystokinin. Our results provide strong evidence for a role of BDNF as a downstream effector of melanocortinergic signaling pathway within the DVC.", "author" : [ { "dropping-particle" : "", "family" : "Bariohay", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roux", "given" : "Julien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tardivel", "given" : "Catherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trouslard", "given" : "J\u00e9r\u00f4me", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jean", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lebrun", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrinology", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009", "6" ] ] }, "page" : "2646-53", "title" : "Brain-derived neurotrophic factor/tropomyosin-related kinase receptor type B signaling is a downstream effector of the brainstem melanocortin system in food intake control.", "type" : "article-journal", "volume" : "150" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bariohay et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bariohay et al. 2009). 2.3.2 Polygenic forms of obesity Three different study types have been used to determine gene variants associated with polygenetic obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677921", "ISSN" : "1875-5488", "PMID" : "22043164", "abstract" : "Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of \"deep phenotyping\" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "154-168", "title" : "Molecular basis of obesity: current status and future prospects.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011b). Candidate gene studies involve choosing genetic variants based on biological, physiological, or pharmacological evidence of their role in weight regulation. Both MC4R and BDNF ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/hmg/ddm132", "ISSN" : "0964-6906", "PMID" : "17519222", "abstract" : "The melanocortin-4 receptor (MC4R) gene pathogenic mutations are the most prevalent forms of monogenic obesity, responsible for approximately 2% of obesity cases, but its role in common obesity is still elusive. We analyzed the contribution of non-synonymous mutations V103I (rs2229616, c.307G > A) and I251L (no rs, c.751A > C) to obesity in 16 797 individuals of European origin from nine independent case-control, population-based and familial cohorts. We observed a consistent negative association of I251L variant (prevalence ranging 0.41-1.21%) with both childhood and adult class III obesity [odds ratio (OR) ranging from 0.25 to 0.76, 0.001 < P-value < 0.05] and with modulation of body mass index (BMI) in general populations, in eight out of nine studies, whereas only one study showed an association between V103I and BMI. Meta-analyses of previous published data with the current ones provided strong evidence of the protective effect of I251L toward obesity (OR = 0.52, P = 3.58 10-5), together with a modest negative association between V103I and obesity (OR = 0.80, P = 0.002). Taken together, gain-of-function mutations I251L and V103I may be responsible for a preventive fraction of obesity of 2%, which mirrors the prevalence of monogenic obesity due to MC4R haploinsufficiency. These results also emphasize the importance of the MC4R signalling tonus to prevent obesity, even in the context of our current obesogenic environment.", "author" : [ { "dropping-particle" : "", "family" : "Stutzmann", "given" : "Fanny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vatin", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morandi", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jouret", "given" : "B\u00e9atrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Landt", "given" : "Olfert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tounian", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy-Marchal", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buzzetti", "given" : "Raffaella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinelli", "given" : "Leonardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bougn\u00e8res", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hum Mol Genet", "id" : "ITEM-1", "issue" : "15", "issued" : { "date-parts" : [ [ "2007", "8", "1" ] ] }, "page" : "1837-1844", "title" : "Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Stutzmann et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Stutzmann et al. 2007) were discovered using candidate gene studies but otherwise the approach has not been successful for identifying obesity predisposing SNPs. Genome wide linkage studies are an extension of family studies in which families who have the phenotypic trait of interest are recruited and the association of various genetic markers with obesity are investigated. This strategy has not yielded many significant results, likely because of the small effect size of individual polygenic genes on obesity and confounding caused by the environment. Lastly, GWAS involve several hundred thousand SNPs across the human genome being investigated in a large population for their association with a phenotypic trait. As of June 2014, more than 2894 GWAS have been conducted ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Yu", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clyne", "given" : "Melinda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yesupriya", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khoury", "given" : "Muin J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Genet", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "124-125", "title" : "A navigator for human genome epidemiology", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Yu et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Yu et al. 2008). GWAS studies improve upon other designs because the large sample size of individuals allows researchers to find statistically significant results despite the small effect size of the gene ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "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-1", "issue" : "7265", "issued" : { "date-parts" : [ [ "2009", "10", "8" ] ] }, "page" : "747-753", "publisher" : "Nature Publishing Group", "title" : "Finding the missing heritability of complex diseases", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Manolio et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Manolio et al. 2009). Recent studies have provided firm evidence that common variants in or near 70 loci modestly increase BMI variation/obesity risk ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677921", "ISSN" : "1875-5488", "PMID" : "22043164", "abstract" : "Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of \"deep phenotyping\" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "154-168", "title" : "Molecular basis of obesity: current status and future prospects.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011b). Despite the highly significant association of many of the SNPs with BMI, the identified genetic variants only account for approximately 2% of the total heritability of obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fendo.2012.00029", "ISSN" : "1664-2392", "PMID" : "22645519", "abstract" : "Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.", "author" : [ { "dropping-particle" : "", "family" : "Elks", "given" : "Cathy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "" } ], "container-title" : "Frontiers in Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "29", "title" : "Variability in the heritability of body mass index: a systematic review and meta-regression", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.686", "ISSN" : "1546-1718", "PMID" : "20935630", "abstract" : "Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and \u223c 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 \u00d7 10\u207b\u2078), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.", "author" : [ { "dropping-particle" : "", "family" : "Speliotes", "given" : "Elizabeth K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berndt", "given" : "Sonja I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monda", "given" : "Keri L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango Allen", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "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" : "Randall", "given" : "Joshua C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vedantam", "given" : "Sailaja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Winkler", "given" : "Thomas W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Workalemahu", "given" : "Tsegaselassie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heid", "given" : "Iris M", "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" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferreira", "given" : "Teresa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weyant", "given" : "Robert J", "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" : "Estrada", "given" : "Karol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liang", "given" : "Liming", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nemesh", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Park", "given" : "Ju-Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gustafsson", "given" : "Stefan", "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" : "Yang", "given" : "Jian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouatia-Naji", "given" : "Nabila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Esko", "given" : "T\u00f5nu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feitosa", "given" : "Mary F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kutalik", "given" : "Zolt\u00e1n", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raychaudhuri", "given" : "Soumya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scherag", "given" : "Andre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Albert Vernon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "Ryan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aben", "given" : "Katja K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Absher", "given" : "Devin M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Amin", "given" : "Najaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dixon", "given" : "Anna L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glazer", "given" : "Nicole L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goddard", "given" : "Michael E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heard-Costa", "given" : "Nancy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoesel", "given" : "Volker", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hottenga", "given" : "Jouke-Jan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Asa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ketkar", "given" : "Shamika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lamina", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Shengxu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moffatt", "given" : "Miriam F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Myers", "given" : "Richard H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "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" : "Marjolein J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Preuss", "given" : "Michael", "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" : "Sandholt", "given" : "Camilla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Laura 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" : "Tyrer", "given" : "Jonathan P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wingerden", "given" : "Sophie", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Charles C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiklund", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barlassina", "given" : "Christina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Matthew N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jansson", "given" : "John-Olov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawrence", "given" : "Robert W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pellikka", "given" : "Niina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shi", "given" : "Jianxin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thiering", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alavere", "given" : "Helene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alibrandi", "given" : "Maria T S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnold", "given" : "Alice M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aspelund", "given" : "Thor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Atwood", "given" : "Larry D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balmforth", "given" : "Anthony J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergmann", "given" : "Sven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biebermann", "given" : "Heike", "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" : "Boes", "given" : "Tanja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornstein", "given" : "Stefan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Morris J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buchanan", "given" : "Thomas a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busonero", "given" : "Fabio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Harry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cappuccio", "given" : "Francesco P", "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" : "Chen", "given" : "Yii-Der Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chih-Mei", "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" : "Coin", "given" : "Lachlan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Connell", "given" : "John", "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" : "Heijer", "given" : "Martin", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duan", "given" : "Jubao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elosua", "given" : "Roberto", "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" : "Facheris", "given" : "Maurizio F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Felix", "given" : "Stephan B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fischer-Posovszky", "given" : "Pamela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Folsom", "given" : "Aaron R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friedrich", "given" : "Nele", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freimer", "given" : "Nelson B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fu", "given" : "Mao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaget", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Gejman", "given" : "Pablo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geus", "given" : "Eco J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gjesing", "given" : "Anette P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goel", "given" : "Anuj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goyette", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gr\u00e4ssler", "given" : "J\u00fcrgen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenawalt", "given" : "Danielle M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudnason", "given" : "Vilmundur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guiducci", "given" : "Candace", "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" : "Hall", "given" : "Alistair S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Havulinna", "given" : "Aki S", "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" : "Andrew C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hengstenberg", "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" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Homuth", "given" : "Georg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hui", "given" : "Jennie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Igl", "given" : "Wilmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iribarren", "given" : "Carlos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Kevin B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarick", "given" : "Ivonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jewell", "given" : "Elizabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "John", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousilahti", "given" : "Pekka", "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" : "Kajantie", "given" : "Eero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplan", "given" : "Lee M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kathiresan", "given" : "Sekar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kettunen", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kinnunen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knowles", "given" : "Joshua W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolcic", "given" : "Ivana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6nig", "given" : "Inke R", "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" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kval\u00f8y", "given" : "Kirsti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laitinen", "given" : "Jaana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanzani", "given" : "Chiara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Launer", "given" : "Lenore J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtim\u00e4ki", "given" : "Terho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lettre", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Jianjun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lokki", "given" : "Marja-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lorentzon", "given" : "Mattias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luben", "given" : "Robert N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ludwig", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manunta", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marek", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin", "given" : "Nicholas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McArdle", "given" : "Wendy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKnight", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meitinger", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Midthjell", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montgomery", "given" : "Grant W", "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 P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulic", "given" : "Rosanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ngwa", "given" : "Julius S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nelis", "given" : "Mari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Matt J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nyholt", "given" : "Dale R", "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" : "O'Rahilly", "given" : "Stephen", "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", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Par\u00e9", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parker", "given" : "Alex N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pichler", "given" : "Irene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietil\u00e4inen", "given" : "Kirsi H", "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" : "Polasek", "given" : "Ozren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rafelt", "given" : "Suzanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raitakari", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ridderstr\u00e5le", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rief", "given" : "Winfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robertson", "given" : "Neil R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rzehak", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanders", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saramies", "given" : "Jouko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Savolainen", "given" : "Markku J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scherag", "given" : "Susann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schipf", "given" : "Sabine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiber", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schunkert", "given" : "Heribert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinisalo", "given" : "Juha", "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" : "Jan H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stephens", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Surakka", "given" : "Ida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swift", "given" : "Amy J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tammesoo", "given" : "Mari-Liis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tardif", "given" : "Jean-Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teder-Laving", "given" : "Maris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teslovich", "given" : "Tanya M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomson", "given" : "Brian", "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" : "Meurs", "given" : "Joyce B J", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ommen", "given" : "Gert-Jan", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vatin", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viikari", "given" : "Jorma", "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" : "Vogel", "given" : "Carla I G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voight", "given" : "Benjamin F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waite", "given" : "Lindsay L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wallaschofski", "given" : "Henri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Widen", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wiegand", "given" : "Susanna", "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" : "Witte", "given" : "Daniel R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Witteman", "given" : "Jacqueline C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xu", "given" : "Jianfeng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Qunyuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zgaga", "given" : "Lina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ziegler", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zitting", "given" : "Paavo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beilby", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Huikuri", "given" : "Heikki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "James", "given" : "Alan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00e4h\u00f6nen", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levinson", "given" : "Douglas F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Macciardi", "given" : "Fabio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieminen", "given" : "Markku S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohlsson", "given" : "Claes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ridker", "given" : "Paul M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beckmann", "given" : "Jacques S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boeing", "given" : "Heiner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boerwinkle", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chanock", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cupples", "given" : "L Adrienne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdmann", "given" : "Jeanette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gr\u00f6nberg", "given" : "Henrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gyllensten", "given" : "Ulf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Per", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Tamara B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hattersley", "given" : "Andrew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayes", "given" : "Richard B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heinrich", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hveem", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiemeney", "given" : "Lambertus a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krude", "given" : "Heiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Metspalu", "given" : "Andres", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munroe", "given" : "Patricia B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouwehand", "given" : "Willem H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penninx", "given" : "Brenda W", "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" : "Quertermous", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reinehr", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "Aila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rudan", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samani", "given" : "Nilesh J", "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" : "Shuldiner", "given" : "Alan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wabitsch", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waeber", "given" : "G\u00e9rard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watkins", "given" : "Hugh", "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" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chatterjee", "given" : "Nilanjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purcell", "given" : "Shaun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schadt", "given" : "Eric E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Visscher", "given" : "Peter M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Assimes", "given" : "Themistocles L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Caroline S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groop", "given" : "Leif C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haritunians", "given" : "Talin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplan", "given" : "Robert C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohlke", "given" : "Karen L", "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" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strachan", "given" : "David P", "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" : "Wichmann", "given" : "H-Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsteinsdottir", "given" : "Unnur", "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" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boehnke", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stefansson", "given" : "Kari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ingelsson", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Loos", "given" : "Ruth J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Genet", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2010", "11" ] ] }, "page" : "937-948", "title" : "Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Speliotes et al. 2010; Elks et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Speliotes et al. 2010; Elks et al. 2012). Nine SNPs identified through GWAS studies (BDNF, NTRK2, LEPR, SH2B1, PCSK1, POMC, MC4R, TUB, SDCCAG8) overlap with monogenic forms of syndromic and non-syndromic obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677895", "ISSN" : "1875-5488", "PMID" : "22043165", "abstract" : "Candidate gene and genome-wide association studies have led to the discovery of nine loci involved in Mendelian forms of obesity and 58 loci contributing to polygenic obesity. These loci explain a small fraction of the heritability for obesity and many genes remain to be discovered. However, efforts in obesity gene identification greatly modified our understanding of this disorder. In this review, we propose an overlook of major lessons learned from 15 years of research in the field of genetics and obesity. We comment on the existence of the genetic continuum between monogenic and polygenic forms of obesity that pinpoints the role of genes involved in the central regulation of food intake and genetic predisposition to obesity. We explain how the identification of novel obesity predisposing genes has clarified unsuspected biological pathways involved in the control of energy balance that have helped to understand past human history and to explore causality in epidemiology. We provide evidence that obesity predisposing genes interact with the environment and influence the response to treatment relevant to disease prediction.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "169-179", "title" : "Genetics of obesity: What have we Learned?", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.274", "ISSN" : "1546-1718", "PMID" : "19079260", "abstract" : "Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.", "author" : [ { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudbjartsson", "given" : "Daniel F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sulem", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Helgadottir", "given" : "Anna", "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" : "Thorlacius", "given" : "Steinunn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsdottir", "given" : "Ingileif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsdottir", "given" : "Thorbjorg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olafsdottir", "given" : "Elinborg J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olafsdottir", "given" : "Gudridur H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Thorvaldur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Frosti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jorgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aben", "given" : "Katja K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verbeek", "given" : "Andr\u00e9 L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roeleveld", "given" : "Nel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kampman", "given" : "Ellen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanek", "given" : "Lisa R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Lewis C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tryggvadottir", "given" : "Laufey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rafnar", "given" : "Thorunn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Diane M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gulcher", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiemeney", "given" : "Lambertus a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "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" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "page" : "18-24", "title" : "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Thorleifsson et al. 2009; Choquet and Meyre 2011a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Thorleifsson et al. 2009; Choquet and Meyre 2011a). However, the most frequently studied SNPs are within the fat mass and obesity associated gene (FTO). Shortly after the incidental discovery of an association of rs9939609 (FTO) and obesity in a GWAS study for type 2 diabetes conducted in a European population ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1126/science.1141634", "ISSN" : "1095-9203", "PMID" : "17434869", "abstract" : "Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.", "author" : [ { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "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" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "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" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harries", "given" : "Lorna W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrett", "given" : "Jeffrey C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellard", "given" : "Sian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Bridget", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patch", "given" : "Ann-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ness", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "Susan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "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" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cardon", "given" : "Lon R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham a", "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" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "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" : "" } ], "container-title" : "Science", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007", "5", "11" ] ] }, "page" : "889-894", "title" : "A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity", "type" : "article-journal", "volume" : "316" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Frayling et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Frayling et al. 2007), a GWAS investigating obesity-related quantitative traits in Sardinia found the same association which the authors then replicated in European Americans and Hispanic Americans ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.0030115", "ISSN" : "1553-7404", "PMID" : "17658951", "abstract" : "The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x10(-7)), hip circumference (p = 3.4 x 10(-8)), and weight (p = 9.1 x 10(-7)). In Sardinia, homozygotes for the rare \"G\" allele of this SNP (minor allele frequency = 0.46) were 1.3 BMI units heavier than homozygotes for the common \"A\" allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6)). Homozygotes for the rare \"A\" allele of this SNP (minor allele frequency = 0.12) were 1.8 BMI units heavier than homozygotes for the common \"G\" allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare \"A\" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common \"G\" allele. In summary, we have completed a whole genome-association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population.", "author" : [ { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Wei-Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uda", "given" : "Manuela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albai", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strait", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Najjar", "given" : "Samer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagaraja", "given" : "Ramaiah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orr\u00fa", "given" : "Marco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Usala", "given" : "Gianluca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dei", "given" : "Mariano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lai", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maschio", "given" : "Andrea", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Busonero", "given" : "Fabio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulas", "given" : "Antonella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehret", "given" : "Georg B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fink", "given" : "Ashley a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weder", "given" : "Alan B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Richard S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galan", "given" : "Pilar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chakravarti", "given" : "Aravinda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakatta", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Genet", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "7" ] ] }, "page" : "e115", "title" : "Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Scuteri et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Scuteri et al. 2007). A study looking at extremely obese young Germans and their controls found a significant association of rs9939609 (FTO) as well as five other SNPs located in FTO with extreme, early onset obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0001361", "ISSN" : "1932-6203", "PMID" : "18159244", "abstract" : "BACKGROUND: Obesity is a major health problem. Although heritability is substantial, genetic mechanisms predisposing to obesity are not very well understood. We have performed a genome wide association study (GWA) for early onset (extreme) obesity. METHODOLOGY/PRINCIPAL FINDINGS: a) GWA (Genome-Wide Human SNP Array 5.0 comprising 440,794 single nucleotide polymorphisms) for early onset extreme obesity based on 487 extremely obese young German individuals and 442 healthy lean German controls; b) confirmatory analyses on 644 independent families with at least one obese offspring and both parents. We aimed to identify and subsequently confirm the 15 SNPs (minor allele frequency > or =10%) with the lowest p-values of the GWA by four genetic models: additive, recessive, dominant and allelic. Six single nucleotide polymorphisms (SNPs) in FTO (fat mass and obesity associated gene) within one linkage disequilibrium (LD) block including the GWA SNP rendering the lowest p-value (rs1121980; log-additive model: nominal p = 1.13 x 10(-7), corrected p = 0.0494; odds ratio (OR)(CT) 1.67, 95% confidence interval (CI) 1.22-2.27; OR(TT) 2.76, 95% CI 1.88-4.03) belonged to the 15 SNPs showing the strongest evidence for association with obesity. For confirmation we genotyped 11 of these in the 644 independent families (of the six FTO SNPs we chose only two representing the LD bock). For both FTO SNPs the initial association was confirmed (both Bonferroni corrected p<0.01). However, none of the nine non-FTO SNPs revealed significant transmission disequilibrium. CONCLUSIONS/SIGNIFICANCE: Our GWA for extreme early onset obesity substantiates that variation in FTO strongly contributes to early onset obesity. This is a further proof of concept for GWA to detect genes relevant for highly complex phenotypes. We concurrently show that nine additional SNPs with initially low p-values in the GWA were not confirmed in our family study, thus suggesting that of the best 15 SNPs in the GWA only the FTO SNPs represent true positive findings.", "author" : [ { "dropping-particle" : "", "family" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nguyen", "given" : "Thuy Trang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scherag", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friedel", "given" : "Susann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Br\u00f6nner", "given" : "G\u00fcnter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcller", "given" : "Timo Dirk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grallert", "given" : "Harald", "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" : "Rief", "given" : "Winfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sch\u00e4fer", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2007", "1" ] ] }, "page" : "e1361", "title" : "Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants", "type" : "article-journal", "volume" : "2" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hinney et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hinney et al. 2007). This study was followed by another research group concluding that rs1421085 and rs17817449 in FTO are both significantly associated with obesity in a European population using family data to exclude a potential undetected stratification effect ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng2048", "ISSN" : "1061-4036", "PMID" : "17496892", "abstract" : "We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.", "author" : [ { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gallina", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6rner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlsson", "given" : "Lena M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiess", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vatin", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "J\u00e9rome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaillant", "given" : "Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruiz", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weill", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy-Marchal", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potoczna", "given" : "Natascha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stunff", "given" : "Catherine", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bougn\u00e8res", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ch\u00e8vre", "given" : "Jean-Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Genet", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2007", "6" ] ] }, "page" : "724-726", "title" : "Variation in FTO contributes to childhood obesity and severe adult obesity", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dina et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dina et al. 2007). The association of rs9939609 has also been confirmed in African and Asian populations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1749-6632.2010.05903.x", "ISSN" : "1749-6632", "PMID" : "21388413", "abstract" : "Genome-wide association studies have been very powerful, uncovering potentially new biology that would not have been possible using a candidate gene approach. A prime example of this is the gene FTO (fat mass and obesity associated), which first came to light in 2007, when single nucleotide polymorphisms in its first intron were robustly associated with body mass index and obesity. Subsequently, as it became clear that this association with body weight, and increasingly food intake, was replicable across multiple populations and different age groups, attention was turned to studying the biology of FTO, about which absolutely nothing was known. This review focuses on the genetic and biochemical approaches as well as animal models that have been used by us and others since 2007 to try and uncover the complex biology of FTO.", "author" : [ { "dropping-particle" : "", "family" : "Tung", "given" : "Yi-Chun Loraine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yeo", "given" : "Giles S H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ann N Y Acad Sci", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011", "3" ] ] }, "page" : "162-171", "title" : "From GWAS to biology: lessons from FTO", "type" : "article-journal", "volume" : "1220" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0096149", "ISSN" : "1932-6203", "PMID" : "24879436", "abstract" : "Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n = 11,161) and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population). GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01\u00d710-7 for BMI, 1.80\u00d710-6 for FM, and 5.29\u00d710-4 for PBF). Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15\u00d710-3 to 4.94\u00d710-2). There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and customized treatment of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Tan", "given" : "Li-Jun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "Hu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "He", "given" : "Hao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Ke-Hao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Jian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Xiang-Ding", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Ji-Gang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shen", "given" : "Hui", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tian", "given" : "Qing", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krousel-Wood", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papasian", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouchard", "given" : "Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9russe", "given" : "Louis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Hong-Wen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "e96149", "title" : "Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Tung and Yeo 2011; Tan et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Tung and Yeo 2011; Tan et al. 2014). Of all the obesity predisposing SNPs, rs9939609 (FTO) has the largest effect size, with those homozygous for the risk allele weighing on average 3kg more than those homozygous for the protective allele ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1126/science.1141634", "ISSN" : "1095-9203", "PMID" : "17434869", "abstract" : "Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.", "author" : [ { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "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" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "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" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harries", "given" : "Lorna W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrett", "given" : "Jeffrey C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellard", "given" : "Sian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Bridget", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patch", "given" : "Ann-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ness", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "Susan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "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" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cardon", "given" : "Lon R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham a", "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" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "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" : "" } ], "container-title" : "Science", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007", "5", "11" ] ] }, "page" : "889-894", "title" : "A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity", "type" : "article-journal", "volume" : "316" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Frayling et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Frayling et al. 2007). FTO belongs to the superfamily of Fe(II) 2-oxogluterate-dependent dioxygenases which catalyze the Fe(II)- and 2-oxoluterate-dependent demethylation of 3-methylthymine, 3-methyluracil, and N6-methyladensoine in single stranded DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). FTO is mostly expressed in the brain, specifically in the arcurate, paraventricular, dorsomedial, and ventromedial hypothalamic nuclei which is responsible for the control of energy homeostasis. Within the arcuate nuclei, FTO is regulated as a function of nutritional status with fasting causing a decrease in FTO expression and high fat diets causing an increase. Specifically, FTO levels appear to be regulated by the availability of essential amino acids. Decreased FTO expression increases food intake while increased FTO expression decreases food intake. Though the biological mechanism of action of FTO regulating total food intake is in line with studies showing an association of FTO SNPs with food intake, it is still unknown how FTO obesity-related SNPs influence FTO. However, based on the location of the SNPs, it appears that the SNPs are likely either up or down regulating FTO expression opposed to being functional mutations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00125-013-2999-5", "ISSN" : "1432-0428", "PMID" : "23896822", "abstract" : "Genome-wide association studies have revealed that single-nucleotide polymorphisms in the first intron of the gene encoding fat mass and obesity-associated protein (FTO) are robustly associated with BMI and obesity. Subsequently, this association with body weight, which is replicable across multiple populations and different age groups, has been unequivocally linked to increased food intake. Although evidence from a number of animal models with perturbed FTO expression indicates a role for FTO in energy homeostasis, to date, no conclusive link has been made between the risk alleles and FTO expression or its physiological role. FTO is a nucleic acid demethylase, and a deficiency in FTO leads to a complex phenotype highlighted by postnatal growth retardation, pointing to some fundamental developmental role. Recent emerging data now points to a role for FTO in the sensing of nutrients and the regulation of translation and growth. In this review, we explore the in vivo and in vitro evidence detailing the complex biology of FTO and discuss how these might link to the regulation of body weight.", "author" : [ { "dropping-particle" : "", "family" : "Gulati", "given" : "Pawan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yeo", "given" : "Giles S H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetologia", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "10" ] ] }, "page" : "2113-2121", "title" : "The biology of FTO: from nucleic acid demethylase to amino acid sensor", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gulati and Yeo 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gulati and Yeo 2013).One of the challenges in understanding the genetics of obesity today is the discrepancy between heritability estimates and the amount of variance which is explained by known genetic variants, identified through GWAS ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/bioinformatics/btr219", "ISSN" : "1367-4811", "PMID" : "21685087", "abstract" : "MOTIVATION: Random effects models have recently been introduced as an approach for analyzing genome wide association studies (GWASs), which allows estimation of overall heritability of traits without explicitly identifying the genetic loci responsible. Using this approach, Yang et al. (2010) have demonstrated that the heritability of height is much higher than the ~10% associated with identified genetic factors. However, Yang et al. (2010) relied on a heuristic for performing estimation in this model. RESULTS: We adopt the model framework of Yang et al. (2010) and develop a method for maximum-likelihood (ML) estimation in this framework. Our method is based on Monte-Carlo expectation-maximization (MCEM; Wei et al., 1990), an expectation-maximization algorithm wherein a Markov chain Monte Carlo approach is used in the E-step. We demonstrate that this method leads to more stable and accurate heritability estimation compared to the approach of Yang et al. (2010), and it also allows us to find ML estimates of the portion of markers which are causal, indicating whether the heritability stems from a small number of powerful genetic factors or a large number of less powerful ones. CONTACT: saharon@post.tau.ac.il.", "author" : [ { "dropping-particle" : "", "family" : "Golan", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosset", "given" : "Saharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Bioinformatics", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011", "7", "1" ] ] }, "page" : "i317-23", "title" : "Accurate estimation of heritability in genome wide studies using random effects models", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Golan and Rosset 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Golan and Rosset 2011). Despite being highly statistically associated with obesity, the SNPs identified by GWAS only account for approximately 2% of the total heritability of obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fendo.2012.00029", "ISSN" : "1664-2392", "PMID" : "22645519", "abstract" : "Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.", "author" : [ { "dropping-particle" : "", "family" : "Elks", "given" : "Cathy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "" } ], "container-title" : "Frontiers in Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "29", "title" : "Variability in the heritability of body mass index: a systematic review and meta-regression", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Elks et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Elks et al. 2012). Because the effect sizes of obesity predisposing SNPs are relatively small ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "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-1", "issue" : "7265", "issued" : { "date-parts" : [ [ "2009", "10", "8" ] ] }, "page" : "747-753", "publisher" : "Nature Publishing Group", "title" : "Finding the missing heritability of complex diseases", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Manolio et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Manolio et al. 2009), it is possible that many SNPs associated with obesity are not detected because of the statistical significance requirements for a genome wide association, p < 5 x 10-8, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/gepi.20297", "ISSN" : "0741-0395", "PMID" : "18300295", "abstract" : "The question of what significance threshold is appropriate for genomewide association studies is somewhat unresolved. Previous theoretical suggestions have yet to be validated in practice, whereas permutation testing does not resolve a discrepancy between the genomewide multiplicity of the experiment and the subset of markers actually tested. We used genotypes from the Wellcome Trust Case-Control Consortium to estimate a genomewide significance threshold for the UK Caucasian population. We subsampled the genotypes at increasing densities, using permutation to estimate the nominal P-value for 5% family-wise error. By extrapolating to infinite density, we estimated the genomewide significance threshold to be about 7.2 x 10(-8). To reduce the computation time, we considered Patterson's eigenvalue estimator of the effective number of tests, but found it to be an order of magnitude too low for multiplicity correction. However, by fitting a Beta distribution to the minimum P-value from permutation replicates, we showed that the effective number is a useful heuristic and suggest that its estimation in this context is an open problem. We conclude that permutation is still needed to obtain genomewide significance thresholds, but with subsampling, extrapolation and estimation of an effective number of tests, the threshold can be standardized for all studies of the same population.", "author" : [ { "dropping-particle" : "", "family" : "Dudbridge", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gusnanto", "given" : "Arief", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genetic Epidemiology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008", "4" ] ] }, "page" : "227-234", "title" : "Estimation of significance thresholds for genomewide association scans", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dudbridge and Gusnanto 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dudbridge and Gusnanto 2008) and low minor allele frequencies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.608", "ISSN" : "1546-1718", "PMID" : "20562875", "abstract" : "SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Jian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benyamin", "given" : "Beben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McEvoy", "given" : "Brian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordon", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henders", "given" : "Anjali K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nyholt", "given" : "Dale R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madden", "given" : "Pamela a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Andrew C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin", "given" : "Nicholas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montgomery", "given" : "Grant W", "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" : "Nat Genet", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "565-569", "title" : "Common SNPs explain a large proportion of the heritability for human height", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Yang et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Yang et al. 2010). New strategies for handling GWAS data including linear model analysis and random effects models to estimate heritability without needing to know all of the genetic variants associated with a phenotype have been proposed ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/bioinformatics/btr219", "ISSN" : "1367-4811", "PMID" : "21685087", "abstract" : "MOTIVATION: Random effects models have recently been introduced as an approach for analyzing genome wide association studies (GWASs), which allows estimation of overall heritability of traits without explicitly identifying the genetic loci responsible. Using this approach, Yang et al. (2010) have demonstrated that the heritability of height is much higher than the ~10% associated with identified genetic factors. However, Yang et al. (2010) relied on a heuristic for performing estimation in this model. RESULTS: We adopt the model framework of Yang et al. (2010) and develop a method for maximum-likelihood (ML) estimation in this framework. Our method is based on Monte-Carlo expectation-maximization (MCEM; Wei et al., 1990), an expectation-maximization algorithm wherein a Markov chain Monte Carlo approach is used in the E-step. We demonstrate that this method leads to more stable and accurate heritability estimation compared to the approach of Yang et al. (2010), and it also allows us to find ML estimates of the portion of markers which are causal, indicating whether the heritability stems from a small number of powerful genetic factors or a large number of less powerful ones. CONTACT: saharon@post.tau.ac.il.", "author" : [ { "dropping-particle" : "", "family" : "Golan", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosset", "given" : "Saharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Bioinformatics", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011", "7", "1" ] ] }, "page" : "i317-23", "title" : "Accurate estimation of heritability in genome wide studies using random effects models", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.608", "ISSN" : "1546-1718", "PMID" : "20562875", "abstract" : "SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Jian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benyamin", "given" : "Beben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McEvoy", "given" : "Brian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordon", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henders", "given" : "Anjali K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nyholt", "given" : "Dale R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madden", "given" : "Pamela a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Andrew C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin", "given" : "Nicholas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montgomery", "given" : "Grant W", "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" : "Nat Genet", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "565-569", "title" : "Common SNPs explain a large proportion of the heritability for human height", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Yang et al. 2010; Golan and Rosset 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Yang et al. 2010; Golan and Rosset 2011). ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.608", "ISSN" : "1546-1718", "PMID" : "20562875", "abstract" : "SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Jian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benyamin", "given" : "Beben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McEvoy", "given" : "Brian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordon", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henders", "given" : "Anjali K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nyholt", "given" : "Dale R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madden", "given" : "Pamela a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Andrew C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin", "given" : "Nicholas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montgomery", "given" : "Grant W", "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" : "Nat Genet", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "565-569", "title" : "Common SNPs explain a large proportion of the heritability for human height", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Yang et al. (2010)", "previouslyFormattedCitation" : "(Yang et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Yang et al. (2010) applied the linear model analysis method to human height which is estimated to be approximately 80% hereditable. Previously, 50 variants accounted for approximately 5% of the phenotypic variance. Using the linear model analysis method produced a heritability estimate of 84% indicating that statistical techniques may be appropriate for verifying heritability estimates from twin and family studies. The inclusion of SNPs that meet a minimum threshold for association with the disease but are not yet confirmed in modeling techniques can improve the accuracy of disease risk predictions, particularly when used in conjunction with novel technology such as machine learning algorithms which allow for models to take advantage of interactions between genetic markers. This technique was applied to GWAS data for Type 1 Diabetes which significantly improved the predictive value of the model compared to only using confirmed SNPs in regression models ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pgen.1000678", "ISSN" : "1553-7404", "PMID" : "19816555", "abstract" : "Genome-wide association studies (GWAS) have been fruitful in identifying disease susceptibility loci for common and complex diseases. A remaining question is whether we can quantify individual disease risk based on genotype data, in order to facilitate personalized prevention and treatment for complex diseases. Previous studies have typically failed to achieve satisfactory performance, primarily due to the use of only a limited number of confirmed susceptibility loci. Here we propose that sophisticated machine-learning approaches with a large ensemble of markers may improve the performance of disease risk assessment. We applied a Support Vector Machine (SVM) algorithm on a GWAS dataset generated on the Affymetrix genotyping platform for type 1 diabetes (T1D) and optimized a risk assessment model with hundreds of markers. We subsequently tested this model on an independent Illumina-genotyped dataset with imputed genotypes (1,008 cases and 1,000 controls), as well as a separate Affymetrix-genotyped dataset (1,529 cases and 1,458 controls), resulting in area under ROC curve (AUC) of approximately 0.84 in both datasets. In contrast, poor performance was achieved when limited to dozens of known susceptibility loci in the SVM model or logistic regression model. Our study suggests that improved disease risk assessment can be achieved by using algorithms that take into account interactions between a large ensemble of markers. We are optimistic that genotype-based disease risk assessment may be feasible for diseases where a notable proportion of the risk has already been captured by SNP arrays.", "author" : [ { "dropping-particle" : "", "family" : "Wei", "given" : "Zhi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Kai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qu", "given" : "Hui-Qi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Haitao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bradfield", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Cecilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frackleton", "given" : "Edward", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hou", "given" : "Cuiping", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glessner", "given" : "Joseph T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiavacci", "given" : "Rosetta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stanley", "given" : "Charles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monos", "given" : "Dimitri", "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" : "Polychronakos", "given" : "Constantin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hakonarson", "given" : "Hakon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Genetics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2009", "10" ] ] }, "page" : "e1000678", "title" : "From disease association to risk assessment: an optimistic view from genome-wide association studies on type 1 diabetes", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wei et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wei et al. 2009). These findings also indicate that there are many more genetic variants associated with obesity to be discovered. Broadening the scope of GWAS to non-European populations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "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-1", "issue" : "7265", "issued" : { "date-parts" : [ [ "2009", "10", "8" ] ] }, "page" : "747-753", "publisher" : "Nature Publishing Group", "title" : "Finding the missing heritability of complex diseases", "type" : "article-journal", "volume" : "461" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Manolio et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Manolio et al. 2009) and working towards larger samples sizes to increase power are amongst the steps that can be taken to improve our understanding of the genetics of obesity. Including SNPs that are nominally significant with obesity/BMI increases the variance attributable to genetics, however the heritability estimates still remain far lower than those determined by family and twin studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.608", "ISSN" : "1546-1718", "PMID" : "20562875", "abstract" : "SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.", "author" : [ { "dropping-particle" : "", "family" : "Yang", "given" : "Jian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benyamin", "given" : "Beben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McEvoy", "given" : "Brian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordon", "given" : "Scott", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henders", "given" : "Anjali K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nyholt", "given" : "Dale R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Madden", "given" : "Pamela a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heath", "given" : "Andrew C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Martin", "given" : "Nicholas G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Montgomery", "given" : "Grant W", "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" : "Nat Genet", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2010", "7" ] ] }, "page" : "565-569", "title" : "Common SNPs explain a large proportion of the heritability for human height", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Yang et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Yang et al. 2010). Other explanations of the “missing heritability” include rare variants which may have a large effect size but are not investigated because of their low minor allele frequency, genetic interactions as total heritability estimates assume that the risk alleles do not interact and have an additive effect, gene by environment interactions in which environmental factors modify the effect of risk alleles on the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/HCO.0b013e328352707d", "ISSN" : "1531-7080", "PMID" : "22450721", "abstract" : "PURPOSE OF REVIEW: To discuss the basis of 'missing heritability', which has emerged as an enigma in the post-genome-wide association studies (GWAS) era. RECENT FINDINGS: Alleles identified through GWAS account for a relatively small fraction of heritability of the complex phenotypes. Accordingly, a significant part of heritability of the complex traits remains unaccounted for ('missing heritability'). Recent findings offer several explanations, including overestimation of heritability of the complex traits and underestimation of the effects of alleles identified through GWAS. In addition, yet-to-be identified common as well as rare alleles might in part explain the 'missing heritability'. Moreover, gene-gene (epistasis) and gene-environmental interactions might explain another fraction of heritability of complex traits. Moreover, transgenerational epigenetic changes, regulated in part by microRNAs, might also contribute to the 'missing heritability'. SUMMARY: The new findings suggest a multifarious nature of the 'missing heritability'. The findings de-emphasize the focus on delineating the basis of 'missing heritability' and shift the focus to elucidation of the molecular mechanisms by which genomic and genetic factors govern the pathogenesis of the complex phenotypes.", "author" : [ { "dropping-particle" : "", "family" : "Marian", "given" : "Ali J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Opin Cardiol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "page" : "197-201", "title" : "Elements of 'missing heritability'", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Marian 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Marian 2012), and copy number variations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2012.162", "ISSN" : "1930-739X", "PMID" : "22836685", "abstract" : "Obesity is a highly heritable trait and a growing public health problem. African Americans (AAs) are a genetically diverse, yet understudied population with a high prevalence of obesity (BMI >30 kg/m(2)). Recent studies based upon single-nucleotide polymorphisms (SNPs) have identified genetic markers associated with obesity. However, a large proportion of the heritability of obesity remains unexplained. Copy number variation (CNV) has been cited as a possible source of missing heritability in common diseases such as obesity. We conducted a CNV genome-wide association study of BMI in two African-American cohorts from Genetic Epidemiology Network of Arteriopathy (GENOA) and Hypertension Genetic Epidemiology Network (HyperGEN). We performed independent and identical association analyses in each study, then combined the results in a meta-analysis. We identified three CNVs associated with BMI, obesity, and other obesity-related traits after adjusting for multiple testing. These CNVs overlap the PARK2, GYPA, and SGCZ genes. Our results suggest that CNV may play a role in the etiology of obesity in AAs.", "author" : [ { "dropping-particle" : "", "family" : "Zhao", "given" : "Wei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wineinger", "given" : "Nathan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiwari", "given" : "Hemant K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mosley", "given" : "Thomas H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Broeckel", "given" : "Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnett", "given" : "Donna K", "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" : "Kabagambe", "given" : "Edmond K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Sun", "given" : "Yan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity (Silver Spring, Md.)", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2012", "12" ] ] }, "page" : "2431-7", "publisher" : "Nature Publishing Group", "title" : "Copy number variations associated with obesity-related traits in African Americans: a joint analysis between GENOA and HyperGEN.", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Zhao et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Zhao et al. 2012).2.4 Current state of knowledge of the genetics of eating behaviourAfter the identification of FTO and other obesity predisposing SNPs, researchers began to look at the association of obesity-predisposing SNPs with eating behaviours in an attempt to better understand the mechanism of action of genes in increasing obesity risk. Behaviours associated with obesity that have been identified to be under genetic control in heritability studies such as energy consumption, macronutrient distribution patterns, food consumption patterns, and eating behaviours have also been found to be associated with obesity predisposing SNPs. Several SNPs have consistently been shown to be associated with increased energy intake including rs9939609 (FTO) in children ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cecil", "given" : "Joanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavendale", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watt", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hetherington", "given" : "Marion M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "N Engl J Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2558-2566", "title" : "An obesity-associated FTO gene variant and increased energy intake in children", "type" : "article-journal", "volume" : "359" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1938-3207", "PMID" : "18842783", "abstract" : "BACKGROUND: A region of chromosome 16 containing the fat mass-and obesity-associated gene (FTO) is reproducibly associated with fat mass and body mass index (BMI), risk of obesity, and adiposity. OBJECTIVES: We aimed to assess the possibility that appetite plays a role in the association between FTO and BMI. DESIGN: Detailed dietary report information from the Avon Longitudinal Study of Parents and Children allowed the exploration of relations between FTO variation and dietary intake. Analyses were performed to investigate possible associations between variation at the FTO locus and the intake of a range of micronutrients and macronutrients, with adjustment for the bias often found within dietary report data when factors related to BMI are assessed. To test the hypothesis that FTO may be influencing appetite directly, rather than indirectly via BMI and altered intake requirements, we also assessed associations between FTO and dietary intake independent of BMI. RESULTS: Relations between a single-nucleotide polymorphism characterizing the FTO signal (rs9939609) and dietary variables were found and can be summarized by the effect of each additional allele (per-allele effects) on total energy and total fat (P < 0.001 for both). These associations were attenuated, but they persisted specifically for fat and energy consumption after adjustment for BMI [total daily fat consumption: approximately 1.5 g/d (P = 0.02 for the per-allele difference); total daily energy consumption: approximately 25 kJ/d (P = 0.03 for the per-allele difference)]. CONCLUSION: These associations suggest that persons carrying minor variants at rs9939609 were consuming more fat and total energy than were those not carrying such variants. They also suggest that this difference was not simply dependent on having higher average BMIs among the former group.", "author" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emmett", "given" : "Pauline 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" : "Rogers", "given" : "Imogen", "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" : "Davey Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "971-978", "title" : "The fat mass- and obesity-associated locus and dietary intake in children", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cecil et al. 2008; Timpson et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cecil et al. 2008; Timpson et al. 2008) and in adults ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2008.318", "ISSN" : "1930-7381", "PMID" : "18551109", "abstract" : "The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the \"at risk\" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rance", "given" : "Kellie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnstone", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "1961-1965", "title" : "Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Speakman et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Speakman et al. 2008), and rs8050136 (FTO) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1055/s-0028-1087176", "ISSN" : "1439-3646", "PMID" : "19053021", "abstract" : "Polymorphisms in the FTO (fat mass- and obesity-associated) gene are associated with obesity. The mechanisms how genetic variation in this gene influences body weight are unknown. Body weight is determined by energy intake/storage and energy expenditure. In this study, we investigated whether genetic variation in FTO influences energy expenditure or food intake in carefully phenotyped subjects. In 380 German subjects, insulin sensitivity was measured by a hyperinsulinemic euglycemic clamp. Lean body mass and body fat were quantified using the bioimpedance method. Indirect calorimetry was used to estimate the metabolic rate. Food intake was assessed using food diaries (mean 11+/-1 d) in 151 subjects participating in a lifestyle intervention program to prevent diabetes. All subjects were genotyped for the FTO single nucleotide polymorphism (SNP) rs8050136. The risk allele of SNP rs8050136 was associated with higher body fat-related parameters (all p< or =0.04, additive inheritance model). Energy expenditure was not affected by the SNP. However, the risk allele of rs8050136 was significantly associated with higher energy intake (p=0.01, dominant inheritance model) during dietary restriction. Our data suggest that the increased body weight in carriers of the risk allele of FTO SNP rs8050136 is a consequence of increased food intake, but not of impaired energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Haupt", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thamer", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staiger", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tschritter", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirchhoff", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Machicao", "given" : "F", "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" : "Stefan", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fritsche", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Exp Clin Endocrinol Diabetes", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "194-197", "title" : "Variation in the FTO gene influences food intake but not energy expenditure", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Haupt et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Haupt et al. 2009). Some genes have also been found to be associated with macronutrient consumption such as rs7498665 (SH2B1) with increased fat, saturated fat, and monounsaturated fat, rs368794 (KCTD15) with increased carbohydrate intake, rs2568958 (NEGR1) with decreased saturated fat and monounsaturated fat intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.2009.27781.INTRODUCTION", "author" : [ { "dropping-particle" : "", "family" : "Bauer", "given" : "Florianne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elbers", "given" : "Clara C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "Roger A H", "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" : "Onland-moret", "given" : "N Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Vliet-ostaptchouk", "given" : "Jana V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van Der", "family" : "Schouw", "given" : "Yvonne T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "951-959", "title" : "Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference 1 \u2013 3", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bauer et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bauer et al. 2009), rs8050136 (FTO) with an increased percentage of calories from fat and decreased percentage of calories from carbohydrates ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/aje/kwt028", "ISSN" : "1476-6256", "PMID" : "23820787", "abstract" : "Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (\u03b2meta = 0.2244 (standard error, 0.0548); P = 4 \u00d7 10(-5)) and inversely associated with percentage of calories derived from carbohydrate (\u03b2meta = -0.2796 (standard error, 0.0709); P = 8 \u00d7 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2), 95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.", "author" : [ { "dropping-particle" : "", "family" : "Park", "given" : "Sungshim Lani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Iona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pendergrass", "given" : "Sarah a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kucharska-Newton", "given" : "Anna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Unhee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ambite", "given" : "Jose Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caberto", "given" : "Christian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monroe", "given" : "Kristine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schumacher", "given" : "Fredrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hindorff", "given" : "Lucia a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oetjens", "given" : "Matthew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodloe", "given" : "Robert J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Love", "given" : "Shelly-Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "Brian E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolonel", "given" : "Laurence N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haiman", "given" : "Christopher a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Dana C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heiss", "given" : "Gerardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ritchie", "given" : "Marylyn D", "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" : "Lo\u00efc", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Epidemiol", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "780-790", "title" : "Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study", "type" : "article-journal", "volume" : "178" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Park et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Park et al. 2013), and rs1421085 (FTO) with higher protein intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.112.052183", "ISSN" : "1938-3207", "PMID" : "23636237", "abstract" : "BACKGROUND: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. OBJECTIVE: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. DESIGN: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 \u00d7 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. RESULTS: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (\u03b2 \u00b1 SE: 0.25 \u00b1 0.04%; P = 1.68 \u00d7 10(-8)) and lower fat (\u03b2 \u00b1 SE: -0.21 \u00b1 0.04%; P = 1.57 \u00d7 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (\u03b2 \u00b1 SE: 0.10 \u00b1 0.02%; P = 9.96 \u00d7 10(-10)), independent of BMI (after adjustment for BMI, \u03b2 \u00b1 SE: 0.08 \u00b1 0.02%; P = 3.15 \u00d7 10(-7)). CONCLUSION: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ngwa", "given" : "Julius S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rooij", "given" : "Frank J a", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wojczynski", "given" : "Mary K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frazier-Wood", "given" : "Alexis C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Houston", "given" : "Denise K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemaitre", "given" : "Rozenn N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mikkil\u00e4", "given" : "Vera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renstrom", "given" : "Frida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chu", "given" : "Audrey Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira Otto", "given" : "Marcia C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhurandhar", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feitosa", "given" : "Mary F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Ingegerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohman", "given" : "Kurt K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manichaikul", "given" : "Ani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "Nicola M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mozaffarian", "given" : "Dariush", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viikari", "given" : "Jorma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Zheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandinelli", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yongmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyytik\u00e4inen", "given" : "Leo-Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitriou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "Goran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00e4h\u00f6nen", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ordovas", "given" : "Jose M", "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" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalafati", "given" : "Ioanna-Panagiota", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raitakari", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franco", "given" : "Oscar H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrack", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Semba", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnett", "given" : "Donna K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid 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" : "Kritchevsky", "given" : "Stephen B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtim\u00e4ki", "given" : "Terho", "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" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cupples", "given" : "L Adrienne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nettleton", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "1395-1402", "title" : "Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Tanaka et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Tanaka et al. 2013). To take into account that generally as BMI increases energy requirements also need to increase, leading to higher energy consumption, models were adjusted either for BMI/body weight ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.112.052183", "ISSN" : "1938-3207", "PMID" : "23636237", "abstract" : "BACKGROUND: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. OBJECTIVE: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. DESIGN: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 \u00d7 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. RESULTS: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (\u03b2 \u00b1 SE: 0.25 \u00b1 0.04%; P = 1.68 \u00d7 10(-8)) and lower fat (\u03b2 \u00b1 SE: -0.21 \u00b1 0.04%; P = 1.57 \u00d7 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (\u03b2 \u00b1 SE: 0.10 \u00b1 0.02%; P = 9.96 \u00d7 10(-10)), independent of BMI (after adjustment for BMI, \u03b2 \u00b1 SE: 0.08 \u00b1 0.02%; P = 3.15 \u00d7 10(-7)). CONCLUSION: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ngwa", "given" : "Julius S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rooij", "given" : "Frank J a", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wojczynski", "given" : "Mary K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frazier-Wood", "given" : "Alexis C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Houston", "given" : "Denise K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemaitre", "given" : "Rozenn N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mikkil\u00e4", "given" : "Vera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renstrom", "given" : "Frida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chu", "given" : "Audrey Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira Otto", "given" : "Marcia C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhurandhar", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feitosa", "given" : "Mary F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Ingegerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohman", "given" : "Kurt K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manichaikul", "given" : "Ani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "Nicola M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mozaffarian", "given" : "Dariush", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viikari", "given" : "Jorma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Zheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandinelli", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yongmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyytik\u00e4inen", "given" : "Leo-Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitriou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "Goran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00e4h\u00f6nen", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ordovas", "given" : "Jose M", "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" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalafati", "given" : "Ioanna-Panagiota", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raitakari", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franco", "given" : "Oscar H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrack", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Semba", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnett", "given" : "Donna K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid 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" : "Kritchevsky", "given" : "Stephen B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtim\u00e4ki", "given" : "Terho", "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" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cupples", "given" : "L Adrienne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nettleton", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "1395-1402", "title" : "Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cecil", "given" : "Joanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavendale", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watt", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hetherington", "given" : "Marion M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "N Engl J Med", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2558-2566", "title" : "An obesity-associated FTO gene variant and increased energy intake in children", "type" : "article-journal", "volume" : "359" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "1938-3207", "PMID" : "18842783", "abstract" : "BACKGROUND: A region of chromosome 16 containing the fat mass-and obesity-associated gene (FTO) is reproducibly associated with fat mass and body mass index (BMI), risk of obesity, and adiposity. OBJECTIVES: We aimed to assess the possibility that appetite plays a role in the association between FTO and BMI. DESIGN: Detailed dietary report information from the Avon Longitudinal Study of Parents and Children allowed the exploration of relations between FTO variation and dietary intake. Analyses were performed to investigate possible associations between variation at the FTO locus and the intake of a range of micronutrients and macronutrients, with adjustment for the bias often found within dietary report data when factors related to BMI are assessed. To test the hypothesis that FTO may be influencing appetite directly, rather than indirectly via BMI and altered intake requirements, we also assessed associations between FTO and dietary intake independent of BMI. RESULTS: Relations between a single-nucleotide polymorphism characterizing the FTO signal (rs9939609) and dietary variables were found and can be summarized by the effect of each additional allele (per-allele effects) on total energy and total fat (P < 0.001 for both). These associations were attenuated, but they persisted specifically for fat and energy consumption after adjustment for BMI [total daily fat consumption: approximately 1.5 g/d (P = 0.02 for the per-allele difference); total daily energy consumption: approximately 25 kJ/d (P = 0.03 for the per-allele difference)]. CONCLUSION: These associations suggest that persons carrying minor variants at rs9939609 were consuming more fat and total energy than were those not carrying such variants. They also suggest that this difference was not simply dependent on having higher average BMIs among the former group.", "author" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emmett", "given" : "Pauline 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" : "Rogers", "given" : "Imogen", "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" : "Davey Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "971-978", "title" : "The fat mass- and obesity-associated locus and dietary intake in children", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1055/s-0028-1087176", "ISSN" : "1439-3646", "PMID" : "19053021", "abstract" : "Polymorphisms in the FTO (fat mass- and obesity-associated) gene are associated with obesity. The mechanisms how genetic variation in this gene influences body weight are unknown. Body weight is determined by energy intake/storage and energy expenditure. In this study, we investigated whether genetic variation in FTO influences energy expenditure or food intake in carefully phenotyped subjects. In 380 German subjects, insulin sensitivity was measured by a hyperinsulinemic euglycemic clamp. Lean body mass and body fat were quantified using the bioimpedance method. Indirect calorimetry was used to estimate the metabolic rate. Food intake was assessed using food diaries (mean 11+/-1 d) in 151 subjects participating in a lifestyle intervention program to prevent diabetes. All subjects were genotyped for the FTO single nucleotide polymorphism (SNP) rs8050136. The risk allele of SNP rs8050136 was associated with higher body fat-related parameters (all p< or =0.04, additive inheritance model). Energy expenditure was not affected by the SNP. However, the risk allele of rs8050136 was significantly associated with higher energy intake (p=0.01, dominant inheritance model) during dietary restriction. Our data suggest that the increased body weight in carriers of the risk allele of FTO SNP rs8050136 is a consequence of increased food intake, but not of impaired energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Haupt", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thamer", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staiger", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tschritter", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirchhoff", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Machicao", "given" : "F", "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" : "Stefan", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fritsche", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Exp Clin Endocrinol Diabetes", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "194-197", "title" : "Variation in the FTO gene influences food intake but not energy expenditure", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cecil et al. 2008; Timpson et al. 2008; Haupt et al. 2009; Tanaka et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cecil et al. 2008; Timpson et al. 2008; Haupt et al. 2009; Tanaka et al. 2013), total energy consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.2009.27781.INTRODUCTION", "author" : [ { "dropping-particle" : "", "family" : "Bauer", "given" : "Florianne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elbers", "given" : "Clara C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "Roger A H", "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" : "Onland-moret", "given" : "N Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Vliet-ostaptchouk", "given" : "Jana V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van Der", "family" : "Schouw", "given" : "Yvonne T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "951-959", "title" : "Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference 1 \u2013 3", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/aje/kwt028", "ISSN" : "1476-6256", "PMID" : "23820787", "abstract" : "Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (\u03b2meta = 0.2244 (standard error, 0.0548); P = 4 \u00d7 10(-5)) and inversely associated with percentage of calories derived from carbohydrate (\u03b2meta = -0.2796 (standard error, 0.0709); P = 8 \u00d7 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2), 95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.", "author" : [ { "dropping-particle" : "", "family" : "Park", "given" : "Sungshim Lani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Iona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pendergrass", "given" : "Sarah a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kucharska-Newton", "given" : "Anna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Unhee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ambite", "given" : "Jose Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caberto", "given" : "Christian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monroe", "given" : "Kristine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schumacher", "given" : "Fredrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hindorff", "given" : "Lucia a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oetjens", "given" : "Matthew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodloe", "given" : "Robert J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Love", "given" : "Shelly-Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "Brian E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolonel", "given" : "Laurence N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haiman", "given" : "Christopher a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Dana C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heiss", "given" : "Gerardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ritchie", "given" : "Marylyn D", "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" : "Lo\u00efc", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Epidemiol", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "780-790", "title" : "Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study", "type" : "article-journal", "volume" : "178" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bauer et al. 2009; Park et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bauer et al. 2009; Park et al. 2013), or basal metabolic rate ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/oby.2008.318", "ISSN" : "1930-7381", "PMID" : "18551109", "abstract" : "The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the \"at risk\" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rance", "given" : "Kellie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnstone", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "1961-1965", "title" : "Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Speakman et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Speakman et al. 2008). By adjusting for BMI in the case of studies looking at the association of SNPs with total energy consumption, we can be more sure that the individual is consuming more food because of the SNP rather than because their increased body size requires it. Similarly, by adjusting for total energy intake when considering the association of SNPs with intakes of macronutrients, it indicates that the individual has a greater proportion of their diet coming from a specific macronutrient rather than simply consuming more energy and consequently a proportionate amount more of each macronutrient. Another method of determining if SNPs influence what is consumed is to look at food categories. There is evidence that the risk variant of rs4788099 (SH2B1) is associated with more servings of dairy products per day, and BDNF risk variants (rs10767664, rs6265, and/or rs1401625) are associated with more servings of meat, eggs, nuts and beans ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mccaffery et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mccaffery et al. 2012). Some genes also seem to influence how and when people eat food. Having the risk variant for rs142085 (FTO) increases the number of eating episodes per day ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mccaffery et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mccaffery et al. 2012), rs17782313 (near MC4R) is associated with an increase in disinhibition and emotional eating scores in females from the Three Factor Eating Questionnaire ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0074362", "ISSN" : "1932-6203", "PMID" : "24066140", "abstract" : "Obesity is associated with genetic and environmental factors but the underlying mechanisms remain poorly understood. Recent genome-wide association studies (GWAS) identified obesity- and type 2 diabetes-associated genetic variants located within or near genes that modulate brain activity and development. Among the top hits is rs17782313 near MC4R, encoding for the melanocortin-4-receptor, which is expressed in brain regions that regulate eating. Here, we hypothesized rs17782313-associated changes in human brain regions that regulate eating behavior. Therefore, we examined effects of common variants at rs17782313 near MC4R on brain structure and eating behavior. Only in female homozygous carriers of the risk allele we found significant increases of gray matter volume (GMV) in the right amygdala, a region known to influence eating behavior, and the right hippocampus, a structure crucial for memory formation and learning. Further, we found bilateral increases in medial orbitofrontal cortex, a multimodal brain structure encoding the subjective value of reinforcers, and bilateral prefrontal cortex, a higher order regulation area. There was no association between rs17782313 and brain structure in men. Moreover, among female subjects only, we observed a significant increase of 'disinhibition', and, more specifically, on 'emotional eating' scores of the Three Factor Eating Questionnaire in carriers of the variant rs17782313's risk allele. These findings suggest that rs17782313's effect on eating behavior is mediated by central mechanisms and that these effects are sex-specific.", "author" : [ { "dropping-particle" : "", "family" : "Horstmann", "given" : "Annette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kabisch", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boettcher", "given" : "Yvonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schloegl", "given" : "Haiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6njes", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stumvoll", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pleger", "given" : "Burkhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Villringer", "given" : "Arno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "e74362", "title" : "Common genetic variation near MC4R has a sex-specific impact on human brain structure and eating behavior.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Horstmann et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Horstmann et al. 2013), nominally significant associations have been found between increased snacking with rs295946 (BDNF) and rs7498665 (SH2B1) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00109-013-1027-z", "ISBN" : "0010901310", "ISSN" : "1432-1440", "PMID" : "23640704", "abstract" : "We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (\u03b2 = 0.180 [0.022-0.339], P value = 0.0258 and \u03b2 = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (\u03b2 = 0.151 [-0.006 to 0.309], P value = 0.0591 and \u03b2 = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.", "author" : [ { "dropping-particle" : "", "family" : "Robiou-du-Pont", "given" : "S\u00e9bastien", "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" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "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" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Mol Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "5", "3" ] ] }, "title" : "Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Robiou-du-Pont et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Robiou-du-Pont et al. 2013), statistically significant increases in snacking with rs17782313 (near MC4R) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2008.279", "ISSN" : "1476-5497", "PMID" : "19153581", "abstract" : "Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P=0.01) and Swiss obese adults (P=0.04) as well as in adolescents from the Finnish general population (P=0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P=0.02) and in obese children with a higher prevalence of eating large amounts of food (P=0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-of-function mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.", "author" : [ { "dropping-particle" : "", "family" : "Stutzmann", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calvacanti-Proen\u00e7a", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pigeyre", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "A-L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weill", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potoczna", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laitinen", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00e4rvelin", "given" : "M-R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Obes", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "3" ] ] }, "page" : "373-378", "title" : "Common genetic variation near MC4R is associated with eating behaviour patterns in European populations", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Stutzmann et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Stutzmann et al. 2009), an association of decreased fullness after food consumption for rs9939609 (FTO) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S0007114513000147", "ISSN" : "1475-2662", "PMID" : "23433430", "abstract" : "An increasing number of studies have reported a heritable component for the regulation of energy intake and eating behaviour, although the individual polymorphisms and their \u2018effect size\u2019 are not fully elucidated. The aim of the present study was to examine the relationship between specific SNP and appetite responses and energy intake in overweight men. In a randomised cross-over trial, forty overweight men (age 32 (sd 09) years; BMI 27 (sd 2) kg/m2) attended four sessions 1 week apart and received three isoenergetic and isovolumetric servings of dairy snacks or water (control) in random order. Appetite ratings were determined using visual analogue scales and energy intake at an ad libitum lunch was assessed 90 min after the dairy snacks. Individuals were genotyped for SNP in the fat mass and obesity-associated (FTO), leptin (LEP), leptin receptor (LEPR) genes and a variant near the melanocortin-4 receptor (MC4R) locus. The postprandial fullness rating over the full experiment following intake of the different snacks was 17\u00b72 % (P= 0\u00b7026) lower in A carriers compared with TT homozygotes for rs9939609 (FTO, dominant) and 18\u00b76 % (P= 0\u00b7020) lower in G carriers compared with AA homozygotes for rs7799039 (LEP, dominant). These observations indicate that FTO and LEP polymorphisms are related to the variation in the feeling of fullness and may play a role in the regulation of food intake. Further studies are required to confirm these initial observations and investigate the \u2018penetrance\u2019 of these genotypes in additional population subgroups.", "author" : [ { "dropping-particle" : "", "family" : "Dougkas", "given" : "Anestis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yaqoob", "given" : "Parveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Givens", "given" : "D Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reynolds", "given" : "Christopher K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Minihane", "given" : "Anne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brit J Nutr", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "9", "28" ] ] }, "page" : "1151-1156", "title" : "The impact of obesity-related SNP on appetite and energy intake", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dougkas et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dougkas et al. 2013), increased food responsiveness in children is associated with rs9939609 (FTO) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0049131", "ISSN" : "1932-6203", "PMID" : "23155456", "abstract" : "The FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg)/height (m)(2)) in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural phenotypes, such as impulsivity and control. We examined the effect of the FTO minor allele (A) at rs9939609 on eating behaviour, impulsivity and control in young children, thus before the BMI effect becomes apparent. This study was embedded in the Generation R Study, a population-based cohort from fetal life onwards. 1,718 children of European descent were genotyped for FTO at rs9939609. With logistic regression assuming an additive genetic model, we examined the association between the FTO minor allele and eating behaviour, impulsivity and control in preschool children. There was no relation between FTO at rs9939609 and child BMI at this age. The A allele at rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03). Also, children with the A allele were less likely to have symptoms of ADHD (OR 0.74, p = 0.01) and showed more emotional control (OR 0.64, p = 0.01) compared to children without the A allele. Our findings suggest that before the association between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to increased food responsiveness, a decreased risk for symptoms of ADHD and better emotional control. Future studies are needed to investigate whether these findings represent one single mechanism or reflect pleiotropic effects of FTO.", "author" : [ { "dropping-particle" : "", "family" : "Velders", "given" : "Fleur P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wit", "given" : "Jolanda E", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jansen", "given" : "Pauline W", "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" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verhulst", "given" : "Frank C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiemeier", "given" : "Henning", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "e49131", "title" : "FTO at rs9939609, food responsiveness, emotional control and symptoms of ADHD in preschool children", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Velders et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Velders et al. 2012) as well as reduced satiety ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2008-0472", "ISSN" : "0021-972X", "PMID" : "18583465", "abstract" : "CONTEXT: Polymorphisms within the FTO gene have consistently been associated with obesity across multiple populations. However, to date, it is not known whether the association between genetic variation in FTO and obesity is mediated through effects on energy intake or energy expenditure. OBJECTIVE: Our objective was to examine the association between alleles of FTO known to increase obesity risk and measures of habitual appetitive behavior. METHODS: The intronic FTO single nucleotide polymorphism (rs9939609) was genotyped in 3337 United Kingdom children in whom measures of habitual appetitive behavior had been assessed using two scales (Satiety Responsiveness and Enjoyment of Food) from the Child Eating Behaviour Questionnaire, a psychometric tool that has been validated against objective measures of food intake. Associations of FTO genotype with indices of adiposity and appetite were assessed by ANOVA. RESULTS: As expected, the A allele was associated with increased adiposity in this cohort and in an independent case-control replication study of United Kingdom children of similar age. AA homozygotes had significantly reduced Satiety Responsiveness scores (P = 0.008, ANOVA). Mediation analysis indicated that the association of the AA genotype with increased adiposity was explained in part through effects on Satiety Responsiveness. CONCLUSIONS: We have used a unique dataset to examine the relationship between a validated measure of children's habitual appetitive behavior and FTO obesity risk genotype and conclude that the commonest known risk allele for obesity is likely to exert at least some of its effects by influencing appetite.", "author" : [ { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carnell", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haworth", "given" : "Claire M a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Endocrinol Metab", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "page" : "3640-3", "title" : "Obesity associated genetic variation in FTO is associated with diminished satiety", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wardle et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wardle et al. 2008) and increased food consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2008.174", "ISSN" : "1476-5497", "PMID" : "18838977", "abstract" : "OBJECTIVE: Polymorphisms in the obesity-associated gene, FTO, have been linked with sensitivity to satiety in children, indicating FTO may be influencing one of the regulatory drivers underlying food intake. In this study, we tested the hypothesis that food intake in a standard eating behaviour paradigm in which palatable food is offered under conditions of satiety would be associated with FTO genotype status, after controlling for differences in body mass index (BMI). METHODS: Participants were 131 children aged 4-5 years, taking part in a behavioural study of food intake for whom DNA was available for genotyping. The phenotypic indicator of intake was the child's consumption of palatable food presented after having eaten a meal. We also assessed physical activity using parental reports of the child's enjoyment of active games, their level of activity relative to other children and a standard measure of fidgetiness. Associations between polymorphisms of the intronic FTO single nucleotide polymorphism (rs9939609) and behaviour (food intake and activity) were assessed by analysis of variance controlling for sex, age and BMI s.d. scores. RESULTS: The distribution of AA (homogenous for A allele), AT (heterogeneous T and A alleles) and TT (homogenous for T allele) genotypes was 18, 50 and 32%, respectively. As predicted, TT homozygotes ate significantly less than heterozygotes (P=0.03) or AA homozygotes (P=0.02). The effect was not diminished by controlling for BMI s.d. scores. There were no significant associations between FTO genotype and any marker of physical activity. CONCLUSIONS: We showed that children with two copies of the lower-risk FTO alleles ate less than those with one or two higher-risk alleles. We conclude that the T allele is protective against overeating by promoting responsiveness to internal signals of satiety.", "author" : [ { "dropping-particle" : "", "family" : "Wardle", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Llewellyn", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanderson", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Obes", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "page" : "42-45", "title" : "The FTO gene and measured food intake in children", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wardle et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wardle et al. 2009). A genotype score, which sums the obesity predisposing alleles for obesity, may also be used to determine if genetics are influencing food related behaviours. Using a gene score, a negative association was found with satiety responsiveness in children while the gene score was positively associated with adiposity and BMI ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jamapediatrics.2013.4944", "ISSN" : "2168-6211", "PMID" : "24535189", "abstract" : "IMPORTANCE: A better understanding of the cause of obesity is a clinical priority. Obesity is highly heritable, and specific genes are being identified. Discovering the mechanisms through which obesity-related genes influence weight would help pinpoint novel targets for intervention. One potential mechanism is satiety responsiveness. Lack of satiety characterizes many monogenic obesity disorders, and lower satiety responsiveness is linked with weight gain in population samples. OBJECTIVE: To test the hypothesis that satiety responsiveness is an intermediate behavioral phenotype associated with genetic predisposition to obesity in children. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional observational study of a population-based cohort of twins born January 1, 1994, to December 31, 1996 (Twins Early Development Study). Participants included 2258 unrelated children (53.3% female; mean [SD] age, 9.9 [0.8] years), one randomly selected from each twin pair. EXPOSURE: Genetic predisposition to obesity. We created a polygenic risk score (PRS) comprising 28 common obesity-related single-nucleotide polymorphisms identified in a meta-analysis of obesity-related genome-wide association studies. MAIN OUTCOMES AND MEASURES: Satiety responsiveness was indexed with a standard psychometric scale (Child Eating Behavior Questionnaire). Using 1990 United Kingdom reference data, body mass index SD scores and waist SD scores were calculated from parent-reported anthropometric data for each child. Information on satiety responsiveness, anthropometrics, and genotype was available for 2258 children. We examined associations among the PRS, adiposity, and satiety responsiveness. RESULTS: The PRS was negatively related to satiety responsiveness (\u03b2 coefficient, -0.060; 95% CI, -0.019 to -0.101) and positively related to adiposity (\u03b2 coefficient, 0.177; 95% CI, 0.136-0.218 for body mass index SD scores and \u03b2 coefficient, 0.167; 95% CI, 0.126-0.208 for waist SD scores). More children in the top 25% of the PRS were overweight than in the lowest 25% (18.5% vs 7.2%; odds ratio, 2.90; 95% CI, 1.98-4.25). Associations between the PRS and adiposity were significantly mediated by satiety responsiveness (P = .006 for body mass index SD scores and P = .005 for waist SD scores). CONCLUSIONS AND RELEVANCE: These results support the hypothesis that low satiety responsiveness is one of the mechanisms through which genetic predisposition leads to weight gain in an environment rich with food. S\u2026", "author" : [ { "dropping-particle" : "", "family" : "Llewellyn", "given" : "Clare H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trzaskowski", "given" : "Maciej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaarsveld", "given" : "Cornelia H M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA Pediatr", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "338-344", "title" : "Satiety mechanisms in genetic risk of obesity", "type" : "article-journal", "volume" : "168" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Llewellyn et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Llewellyn et al. 2014), and an unexpectedly negative association with total energy intake and higher fibre intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12263-013-0352-8", "ISSN" : "1555-8932", "PMID" : "23861046", "abstract" : "Gene-environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malm\u00f6 Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 \u00d7 10(-34)), fat mass (P = 6.3 \u00d7 10(-28)) and fat-free mass (P = 1.3 \u00d7 10(-24)). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 \u00d7 10(-4)). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet.", "author" : [ { "dropping-particle" : "", "family" : "Rukh", "given" : "Gull", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedblad", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wirf\u00e4lt", "given" : "Elisabet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ericson", "given" : "Ulrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genes & Nutrition", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "7", "17" ] ] }, "page" : "535-547", "title" : "Genetic susceptibility to obesity and diet intakes: association and interaction analyses in the Malm\u00f6 Diet and Cancer Study", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rukh et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rukh et al. 2013).In summary, numerous associations have been found between obesity predisposing genes and food intake behaviour, however many results have not been replicated and the studies have mostly been conducted in European populations. An exception is FTO which has consistently been shown to be associated with food consumption parameters including total energy intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cecil", "given" : "Joanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavendale", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watt", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hetherington", "given" : "Marion M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "N Engl J Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2558-2566", "title" : "An obesity-associated FTO gene variant and increased energy intake in children", "type" : "article-journal", "volume" : "359" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1938-3207", "PMID" : "18842783", "abstract" : "BACKGROUND: A region of chromosome 16 containing the fat mass-and obesity-associated gene (FTO) is reproducibly associated with fat mass and body mass index (BMI), risk of obesity, and adiposity. OBJECTIVES: We aimed to assess the possibility that appetite plays a role in the association between FTO and BMI. DESIGN: Detailed dietary report information from the Avon Longitudinal Study of Parents and Children allowed the exploration of relations between FTO variation and dietary intake. Analyses were performed to investigate possible associations between variation at the FTO locus and the intake of a range of micronutrients and macronutrients, with adjustment for the bias often found within dietary report data when factors related to BMI are assessed. To test the hypothesis that FTO may be influencing appetite directly, rather than indirectly via BMI and altered intake requirements, we also assessed associations between FTO and dietary intake independent of BMI. RESULTS: Relations between a single-nucleotide polymorphism characterizing the FTO signal (rs9939609) and dietary variables were found and can be summarized by the effect of each additional allele (per-allele effects) on total energy and total fat (P < 0.001 for both). These associations were attenuated, but they persisted specifically for fat and energy consumption after adjustment for BMI [total daily fat consumption: approximately 1.5 g/d (P = 0.02 for the per-allele difference); total daily energy consumption: approximately 25 kJ/d (P = 0.03 for the per-allele difference)]. CONCLUSION: These associations suggest that persons carrying minor variants at rs9939609 were consuming more fat and total energy than were those not carrying such variants. They also suggest that this difference was not simply dependent on having higher average BMIs among the former group.", "author" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emmett", "given" : "Pauline 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" : "Rogers", "given" : "Imogen", "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" : "Davey Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "971-978", "title" : "The fat mass- and obesity-associated locus and dietary intake in children", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/oby.2008.318", "ISSN" : "1930-7381", "PMID" : "18551109", "abstract" : "The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the \"at risk\" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rance", "given" : "Kellie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnstone", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "1961-1965", "title" : "Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1055/s-0028-1087176", "ISSN" : "1439-3646", "PMID" : "19053021", "abstract" : "Polymorphisms in the FTO (fat mass- and obesity-associated) gene are associated with obesity. The mechanisms how genetic variation in this gene influences body weight are unknown. Body weight is determined by energy intake/storage and energy expenditure. In this study, we investigated whether genetic variation in FTO influences energy expenditure or food intake in carefully phenotyped subjects. In 380 German subjects, insulin sensitivity was measured by a hyperinsulinemic euglycemic clamp. Lean body mass and body fat were quantified using the bioimpedance method. Indirect calorimetry was used to estimate the metabolic rate. Food intake was assessed using food diaries (mean 11+/-1 d) in 151 subjects participating in a lifestyle intervention program to prevent diabetes. All subjects were genotyped for the FTO single nucleotide polymorphism (SNP) rs8050136. The risk allele of SNP rs8050136 was associated with higher body fat-related parameters (all p< or =0.04, additive inheritance model). Energy expenditure was not affected by the SNP. However, the risk allele of rs8050136 was significantly associated with higher energy intake (p=0.01, dominant inheritance model) during dietary restriction. Our data suggest that the increased body weight in carriers of the risk allele of FTO SNP rs8050136 is a consequence of increased food intake, but not of impaired energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Haupt", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thamer", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staiger", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tschritter", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirchhoff", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Machicao", "given" : "F", "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" : "Stefan", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fritsche", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Exp Clin Endocrinol Diabetes", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "194-197", "title" : "Variation in the FTO gene influences food intake but not energy expenditure", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cecil et al. 2008; Speakman et al. 2008; Timpson et al. 2008; Haupt et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cecil et al. 2008; Speakman et al. 2008; Timpson et al. 2008; Haupt et al. 2009), total fat intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/aje/kwt028", "ISSN" : "1476-6256", "PMID" : "23820787", "abstract" : "Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (\u03b2meta = 0.2244 (standard error, 0.0548); P = 4 \u00d7 10(-5)) and inversely associated with percentage of calories derived from carbohydrate (\u03b2meta = -0.2796 (standard error, 0.0709); P = 8 \u00d7 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2), 95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.", "author" : [ { "dropping-particle" : "", "family" : "Park", "given" : "Sungshim Lani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Iona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pendergrass", "given" : "Sarah a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kucharska-Newton", "given" : "Anna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Unhee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ambite", "given" : "Jose Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caberto", "given" : "Christian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monroe", "given" : "Kristine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schumacher", "given" : "Fredrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hindorff", "given" : "Lucia a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oetjens", "given" : "Matthew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodloe", "given" : "Robert J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Love", "given" : "Shelly-Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "Brian E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolonel", "given" : "Laurence N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haiman", "given" : "Christopher a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Dana C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heiss", "given" : "Gerardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ritchie", "given" : "Marylyn D", "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" : "Lo\u00efc", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Epidemiol", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "780-790", "title" : "Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study", "type" : "article-journal", "volume" : "178" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1017/S001667231100036X", "ISSN" : "1469-5073", "PMID" : "22189607", "abstract" : "The fat mass and obesity associated (FTO) gene has been implicated with obesity and dietary intake predominantly in European populations. We assessed the association between the FTO rs9939609 variant with body fat distribution and dietary intake in a multi-ethnic population. Aboriginal, Chinese, European and South Asian participants living in Canada (n = 706) were assessed for body fat and inner-abdominal fat using imaging techniques, dietary intake and genotyped for the FTO rs9939609 variant. Linear regression was used to study the associations between the minor allele of the variant and measures of adiposity and dietary intake. Minor allele frequencies were: Aboriginals (17%), Chinese (17%), Europeans (39%) and South Asians (31%). The rs9939609 variant was associated with intake of dietary macronutrients in Aboriginals and Europeans only. In the total population, there were positive associations between the rs9939609 minor allele and greater fat mass (0.94 \u00b1 0.56 kg, P = 0.045), per cent body fat (0.7 \u00b1 0.4%, P = 0.031), relative greater subcutaneous abdominal adipose tissue (4.9 \u00b1 2.8%, P = 0.039) and percent daily calories from fat (0.4 \u00b1 0.2%, P = 0.064). Our findings suggest that the FTO rs9939609 minor allele may be associated with dietary intake in adults and is positively associated with regional fat deposition.", "author" : [ { "dropping-particle" : "", "family" : "Lear", "given" : "Scott a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deng", "given" : "Wei Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Par\u00e9", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sulistyoningrum", "given" : "Dian C", "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" : "Devlin", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genet Rest Camb", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "419-426", "title" : "Associations of the FTO rs9939609 variant with discrete body fat depots and dietary intake in a multi-ethnic cohort", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/a.2010.07.010", "ISSN" : "1873-3492", "PMID" : "20650268", "abstract" : "BACKGROUND: Associations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors. METHODS: We genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database. RESULTS: With a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P=0.025, OR=1.47, 95% CI=1.05-2.06; P=0.023, OR=1.53, 95% CI=1.06-2.22) and adults (P=0.018, OR=1.10, 95% CI=1.02-1.19; P=0.001, OR=1.16, 95% CI=1.06-1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P=0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P=0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found. CONCLUSIONS: FTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI.", "author" : [ { "dropping-particle" : "", "family" : "Lee", "given" : "Hye-Ja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "In Kyoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kang", "given" : "Jae Heon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ahn", "given" : "Younjhin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Bok-Ghee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Jong-Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Jihyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinica Chimica Acta", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2010", "11", "11" ] ] }, "page" : "1716-1722", "publisher" : "Elsevier B.V.", "title" : "Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans", "type" : "article-journal", "volume" : "411" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "1938-3207", "PMID" : "18842783", "abstract" : "BACKGROUND: A region of chromosome 16 containing the fat mass-and obesity-associated gene (FTO) is reproducibly associated with fat mass and body mass index (BMI), risk of obesity, and adiposity. OBJECTIVES: We aimed to assess the possibility that appetite plays a role in the association between FTO and BMI. DESIGN: Detailed dietary report information from the Avon Longitudinal Study of Parents and Children allowed the exploration of relations between FTO variation and dietary intake. Analyses were performed to investigate possible associations between variation at the FTO locus and the intake of a range of micronutrients and macronutrients, with adjustment for the bias often found within dietary report data when factors related to BMI are assessed. To test the hypothesis that FTO may be influencing appetite directly, rather than indirectly via BMI and altered intake requirements, we also assessed associations between FTO and dietary intake independent of BMI. RESULTS: Relations between a single-nucleotide polymorphism characterizing the FTO signal (rs9939609) and dietary variables were found and can be summarized by the effect of each additional allele (per-allele effects) on total energy and total fat (P < 0.001 for both). These associations were attenuated, but they persisted specifically for fat and energy consumption after adjustment for BMI [total daily fat consumption: approximately 1.5 g/d (P = 0.02 for the per-allele difference); total daily energy consumption: approximately 25 kJ/d (P = 0.03 for the per-allele difference)]. CONCLUSION: These associations suggest that persons carrying minor variants at rs9939609 were consuming more fat and total energy than were those not carrying such variants. They also suggest that this difference was not simply dependent on having higher average BMIs among the former group.", "author" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emmett", "given" : "Pauline 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" : "Rogers", "given" : "Imogen", "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" : "Davey Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "971-978", "title" : "The fat mass- and obesity-associated locus and dietary intake in children", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.3945/ajcn.2009.28439.1", "author" : [ { "dropping-particle" : "", "family" : "Tanofsky-Kraff", "given" : "Marian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Joan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anandalingam", "given" : "Kavitha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shomaker", "given" : "Lauren B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Columbo", "given" : "Kelli M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolkoff", "given" : "Laura E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozlosky", "given" : "Merel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Camden", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ranzenhofer", "given" : "Lisa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roza", "given" : "Caroline A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Susan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Jack A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-5", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1483-1488", "title" : "The FTO gene rs9939609 obesity-risk allele and loss of control over eating", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Timpson et al. 2008; Tanofsky-Kraff et al. 2009; Lee et al. 2010; Lear et al. 2011; Park et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Timpson et al. 2008; Tanofsky-Kraff et al. 2009; Lee et al. 2010; Lear et al. 2011; Park et al. 2013), protein intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.112.052183", "ISSN" : "1938-3207", "PMID" : "23636237", "abstract" : "BACKGROUND: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. OBJECTIVE: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. DESIGN: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 \u00d7 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. RESULTS: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (\u03b2 \u00b1 SE: 0.25 \u00b1 0.04%; P = 1.68 \u00d7 10(-8)) and lower fat (\u03b2 \u00b1 SE: -0.21 \u00b1 0.04%; P = 1.57 \u00d7 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (\u03b2 \u00b1 SE: 0.10 \u00b1 0.02%; P = 9.96 \u00d7 10(-10)), independent of BMI (after adjustment for BMI, \u03b2 \u00b1 SE: 0.08 \u00b1 0.02%; P = 3.15 \u00d7 10(-7)). CONCLUSION: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ngwa", "given" : "Julius S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rooij", "given" : "Frank J a", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wojczynski", "given" : "Mary K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frazier-Wood", "given" : "Alexis C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Houston", "given" : "Denise K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemaitre", "given" : "Rozenn N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mikkil\u00e4", "given" : "Vera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renstrom", "given" : "Frida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chu", "given" : "Audrey Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira Otto", "given" : "Marcia C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhurandhar", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feitosa", "given" : "Mary F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Ingegerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohman", "given" : "Kurt K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manichaikul", "given" : "Ani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "Nicola M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mozaffarian", "given" : "Dariush", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viikari", "given" : "Jorma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Zheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandinelli", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yongmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyytik\u00e4inen", "given" : "Leo-Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitriou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "Goran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00e4h\u00f6nen", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ordovas", "given" : "Jose M", "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" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalafati", "given" : "Ioanna-Panagiota", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raitakari", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franco", "given" : "Oscar H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrack", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Semba", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnett", "given" : "Donna K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid 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" : "Kritchevsky", "given" : "Stephen B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtim\u00e4ki", "given" : "Terho", "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" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cupples", "given" : "L Adrienne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nettleton", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "1395-1402", "title" : "Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/hmg/ddt032", "ISSN" : "1460-2083", "PMID" : "23372041", "abstract" : "Dietary intake of macronutrients (carbohydrate, protein, and fat) has been associated with risk of chronic conditions such as obesity and diabetes. Family studies have reported a moderate contribution of genetics to variation in macronutrient intake. In a genome-wide meta-analysis of a population-based discovery cohort (n = 33 533), rs838133 in FGF21 (19q13.33), rs197273 near TRAF family member-associated NF-kappa-B activator (TANK) (2p24.2), and rs10163409 in FTO (16q12.2) were among the top associations (P < 10(-5)) for percentage of total caloric intake from protein and carbohydrate. rs838133 was replicated in silico in an independent sample from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) Nutrition Working Group (n = 38 360) and attained genome-wide significance in combined analysis (Pjoint = 7.9 \u00d7 10(-9)). A cytokine involved in cellular metabolism, FGF21 is a potential susceptibility gene for obesity and type 2 diabetes. Our results highlight the potential of genetic variation for determining dietary macronutrient intake.", "author" : [ { "dropping-particle" : "", "family" : "Chu", "given" : "Audrey Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Workalemahu", "given" : "Tsegaselassie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paynter", "given" : "Nina P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Lynda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giulianini", "given" : "Franco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ngwa", "given" : "Julius S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Qibin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curhan", "given" : "Gary C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimm", "given" : "Eric B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasquale", "given" : "Louis R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ridker", "given" : "Paul M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hum Mol Genet", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "5", "1" ] ] }, "page" : "1895-1902", "title" : "Novel locus including FGF21 is associated with dietary macronutrient intake", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Chu et al. 2013; Tanaka et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Chu et al. 2013; Tanaka et al. 2013), carbohydrate intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/aje/kwt028", "ISSN" : "1476-6256", "PMID" : "23820787", "abstract" : "Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (\u03b2meta = 0.2244 (standard error, 0.0548); P = 4 \u00d7 10(-5)) and inversely associated with percentage of calories derived from carbohydrate (\u03b2meta = -0.2796 (standard error, 0.0709); P = 8 \u00d7 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2), 95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.", "author" : [ { "dropping-particle" : "", "family" : "Park", "given" : "Sungshim Lani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Iona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pendergrass", "given" : "Sarah a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kucharska-Newton", "given" : "Anna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Unhee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ambite", "given" : "Jose Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caberto", "given" : "Christian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monroe", "given" : "Kristine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schumacher", "given" : "Fredrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hindorff", "given" : "Lucia a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oetjens", "given" : "Matthew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodloe", "given" : "Robert J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Love", "given" : "Shelly-Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "Brian E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolonel", "given" : "Laurence N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haiman", "given" : "Christopher a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Dana C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heiss", "given" : "Gerardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ritchie", "given" : "Marylyn D", "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" : "Lo\u00efc", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Epidemiol", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "780-790", "title" : "Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study", "type" : "article-journal", "volume" : "178" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Park et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Park et al. 2013), food category consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Brunkwall", "given" : "Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ericson", "given" : "Ulrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hellstrand", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gullberg", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orho-melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Food & Nutrition Research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "20028", "title" : "Genetic variation in the fat mass and obesity-associated gene (FTO) in association with food preferences in healthy adults", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Brunkwall et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Brunkwall et al. 2013), satiety ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2008-0472", "ISSN" : "0021-972X", "PMID" : "18583465", "abstract" : "CONTEXT: Polymorphisms within the FTO gene have consistently been associated with obesity across multiple populations. However, to date, it is not known whether the association between genetic variation in FTO and obesity is mediated through effects on energy intake or energy expenditure. OBJECTIVE: Our objective was to examine the association between alleles of FTO known to increase obesity risk and measures of habitual appetitive behavior. METHODS: The intronic FTO single nucleotide polymorphism (rs9939609) was genotyped in 3337 United Kingdom children in whom measures of habitual appetitive behavior had been assessed using two scales (Satiety Responsiveness and Enjoyment of Food) from the Child Eating Behaviour Questionnaire, a psychometric tool that has been validated against objective measures of food intake. Associations of FTO genotype with indices of adiposity and appetite were assessed by ANOVA. RESULTS: As expected, the A allele was associated with increased adiposity in this cohort and in an independent case-control replication study of United Kingdom children of similar age. AA homozygotes had significantly reduced Satiety Responsiveness scores (P = 0.008, ANOVA). Mediation analysis indicated that the association of the AA genotype with increased adiposity was explained in part through effects on Satiety Responsiveness. CONCLUSIONS: We have used a unique dataset to examine the relationship between a validated measure of children's habitual appetitive behavior and FTO obesity risk genotype and conclude that the commonest known risk allele for obesity is likely to exert at least some of its effects by influencing appetite.", "author" : [ { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carnell", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haworth", "given" : "Claire M a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Endocrinol Metab", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "page" : "3640-3", "title" : "Obesity associated genetic variation in FTO is associated with diminished satiety", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3945/ajcn.2009.28053.1", "author" : [ { "dropping-particle" : "Den", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westerterp-Plantenga", "given" : "Margriet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwman", "given" : "Freek G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariman", "given" : "Edwin C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westerterp", "given" : "Klaas R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1426-1432", "title" : "Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.pec.2010.03.013", "ISSN" : "1873-5134", "PMID" : "20409671", "abstract" : "BACKGROUND: Acute psychological stress is associated with eating in the absence of hunger. OBJECTIVE: To investigate if BclI and FTO polymorphisms are associated with eating in the absence of hunger as a result of acute psychological stress. METHODS: FTO (rs9939609) and BclI were genotyped in 98 subjects (BMI=23.9+/-3.3kg/m(2)). In a randomized crossover design, the 'eating in absence of hunger' protocol was measured as a function of acute stress vs. a control task and of STAI (State Trait Anxiety Index) state scores. RESULTS: In comparison with the FTO T allele, the A allele was associated with an increased feelings of hunger after food intake in the stress (11+/-10 vs. 18+/-15, p<0.01) and control condition (12+/-9 vs. 16+/-12, p<0.05), even though food intake was not different. For the first time, it was observed that in comparison to the BclI C/C genotype, the BclI G/G genotype was associated with higher STAI states scores at 0, 10, and 20min after the stress condition (30.8+/-6.4 vs. 36.3+/-8.2; 28.3+/-5.5 vs. 32.3+/-7.5; 27.7+/-6.1 vs. 31.2+/-7.5, p<0.05). Additionally, the BclI G/G genotype was associated with a larger difference in energy intake between the stress and control condition, in comparison with the BclI C/C genotype (136.6+/-220.4 vs. 29.4+/-176.3kJ, p<0.04). CONCLUSION: In concordance with previous studies, the FTO A allele is related to a lower feeling of hunger after a standardized meal. For the first time, the BclI G/G genotype is shown to be associated with increased sensitivity to psychological stress, and increased eating in the absence of hunger after stress. PRACTICE IMPLICATIONS: Interventions to reduce body weight should consider the subjects' genetic background.", "author" : [ { "dropping-particle" : "", "family" : "Rutters", "given" : "Femke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemmens", "given" : "Sofie G T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Born", "given" : "Jurriaan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouwman", "given" : "Freek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nieuwenhuizen", "given" : "Arie G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mariman", "given" : "Edwin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westerterp-Plantenga", "given" : "Margriet S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Patient Educ Couns", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "6" ] ] }, "page" : "367-371", "publisher" : "Elsevier Ireland Ltd", "title" : "Genetic associations with acute stress-related changes in eating in the absence of hunger.", "type" : "article-journal", "volume" : "79" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1017/S0007114513000147", "ISSN" : "1475-2662", "PMID" : "23433430", "abstract" : "An increasing number of studies have reported a heritable component for the regulation of energy intake and eating behaviour, although the individual polymorphisms and their \u2018effect size\u2019 are not fully elucidated. The aim of the present study was to examine the relationship between specific SNP and appetite responses and energy intake in overweight men. In a randomised cross-over trial, forty overweight men (age 32 (sd 09) years; BMI 27 (sd 2) kg/m2) attended four sessions 1 week apart and received three isoenergetic and isovolumetric servings of dairy snacks or water (control) in random order. Appetite ratings were determined using visual analogue scales and energy intake at an ad libitum lunch was assessed 90 min after the dairy snacks. Individuals were genotyped for SNP in the fat mass and obesity-associated (FTO), leptin (LEP), leptin receptor (LEPR) genes and a variant near the melanocortin-4 receptor (MC4R) locus. The postprandial fullness rating over the full experiment following intake of the different snacks was 17\u00b72 % (P= 0\u00b7026) lower in A carriers compared with TT homozygotes for rs9939609 (FTO, dominant) and 18\u00b76 % (P= 0\u00b7020) lower in G carriers compared with AA homozygotes for rs7799039 (LEP, dominant). These observations indicate that FTO and LEP polymorphisms are related to the variation in the feeling of fullness and may play a role in the regulation of food intake. Further studies are required to confirm these initial observations and investigate the \u2018penetrance\u2019 of these genotypes in additional population subgroups.", "author" : [ { "dropping-particle" : "", "family" : "Dougkas", "given" : "Anestis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yaqoob", "given" : "Parveen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Givens", "given" : "D Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reynolds", "given" : "Christopher K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Minihane", "given" : "Anne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brit J Nutr", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "9", "28" ] ] }, "page" : "1151-1156", "title" : "The impact of obesity-related SNP on appetite and energy intake", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wardle et al. 2008; Hoed et al. 2009; Rutters et al. 2010; Dougkas et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wardle et al. 2008; Hoed et al. 2009; Rutters et al. 2010; Dougkas et al. 2013), number of eating episodes per day ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mccaffery et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mccaffery et al. 2012), and restraint/control of food consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/oby.20592", "ISSN" : "1930-739X", "PMID" : "23929626", "abstract" : "OBJECTIVE: Many confirmed genetic loci for obesity are expressed in regions of the brain that regulate energy intake and reward-seeking behavior. Whether these loci contribute to the development of specific eating behaviors has not been investigated. The relationship between a genetic susceptibility to obesity and cognitive restraint, uncontrolled and emotional eating was examined. METHODS: Eating behavior and body mass index (BMI) were determined by questionnaires for 1471 men and 2381 women from two US cohorts. Genotypes were extracted from genome-wide scans and a genetic-risk score (GRS) derived from 32 obesity-loci was calculated. RESULTS: The GRS was positively associated with emotional and uncontrolled eating (P<0.002). In exploratory analysis, BMI-increasing variants of MTCH2, TNNI3K, and ZC3H4 were positively associated with emotional eating and those of TNNI3K and ZC3H4 were positively associated with uncontrolled eating. The BMI-increasing variant of FTO was positively and those of LRP1B and TFAP2B were inversely associated with cognitive restraint. These associations for single SNPs were independent of BMI but were not significant after multiple-testing correction. CONCLUSIONS: An overall genetic susceptibility to obesity may also extend to eating behaviors. The link between specific loci and obesity may be mediated by eating behavior but larger studies are warranted to confirm these results.", "author" : [ { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimm", "given" : "Eric B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curhan", "given" : "Gary C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "135-141", "title" : "Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1371/journal.pone.0049131", "ISSN" : "1932-6203", "PMID" : "23155456", "abstract" : "The FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg)/height (m)(2)) in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural phenotypes, such as impulsivity and control. We examined the effect of the FTO minor allele (A) at rs9939609 on eating behaviour, impulsivity and control in young children, thus before the BMI effect becomes apparent. This study was embedded in the Generation R Study, a population-based cohort from fetal life onwards. 1,718 children of European descent were genotyped for FTO at rs9939609. With logistic regression assuming an additive genetic model, we examined the association between the FTO minor allele and eating behaviour, impulsivity and control in preschool children. There was no relation between FTO at rs9939609 and child BMI at this age. The A allele at rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03). Also, children with the A allele were less likely to have symptoms of ADHD (OR 0.74, p = 0.01) and showed more emotional control (OR 0.64, p = 0.01) compared to children without the A allele. Our findings suggest that before the association between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to increased food responsiveness, a decreased risk for symptoms of ADHD and better emotional control. Future studies are needed to investigate whether these findings represent one single mechanism or reflect pleiotropic effects of FTO.", "author" : [ { "dropping-particle" : "", "family" : "Velders", "given" : "Fleur P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wit", "given" : "Jolanda E", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jansen", "given" : "Pauline W", "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" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verhulst", "given" : "Frank C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiemeier", "given" : "Henning", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "e49131", "title" : "FTO at rs9939609, food responsiveness, emotional control and symptoms of ADHD in preschool children", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3945/ajcn.2009.28439.1", "author" : [ { "dropping-particle" : "", "family" : "Tanofsky-Kraff", "given" : "Marian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Joan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anandalingam", "given" : "Kavitha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shomaker", "given" : "Lauren B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Columbo", "given" : "Kelli M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wolkoff", "given" : "Laura E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kozlosky", "given" : "Merel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Camden", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ranzenhofer", "given" : "Lisa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roza", "given" : "Caroline A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Susan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Jack A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "1483-1488", "title" : "The FTO gene rs9939609 obesity-risk allele and loss of control over eating", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Tanofsky-Kraff et al. 2009; Velders et al. 2012; Cornelis et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Tanofsky-Kraff et al. 2009; Velders et al. 2012; Cornelis et al. 2014). The lack of replications is indicative of the unavailability of food consumption data in large genotyped populations, differences in measurement of dietary parameters, as well as small sample sizes exacerbated by the small effect size of obesity-predisposing SNPs. However, the scatter results also show that though some SNPs may work through modifying food consumption patterns, some genes may be operating through other mechanisms such as altering metabolism. 2.5 Background of eating disorders2.5.1 Diagnostic criteria The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, version 5) currently describes three eating disorders, anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). AN is characterized by patients being severely underweight (<85% of expected weight), having an intense fear of gaining weight or becoming fat, a disturbance in body image, a heavy emphasis on body shape for self-evaluation, and denial of the seriousness of their current weight loss ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "American Psychiatric Association", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "American Psychiatric Association", "publisher-place" : "Arlington, Virginia", "title" : "Diagnostic and statistical manual of mental disorders", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "(American Psychiatric Association, 2013)", "previouslyFormattedCitation" : "(American Psychiatric Association 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(American Psychiatric Association, 2013). There are two types of AN, binge-eating/purging type (ANBP) involving overeating and purging, and the restricting type (ANR) involving dieting without binging or compensatory behaviours. It is unclear if these are distinct subgroups or different phases of the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hartmann", "given" : "A S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenberg", "given" : "J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilhelm", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Psychology Review", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "675-685", "title" : "The relationship between anorexia nervosa and body dysmorphic disorder", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hartmann et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hartmann et al. 2013). Similar to AN, people with BN place a heavier emphasis on body shape for self-evaluation. The other key characteristic of BN is having recurrent episodes of binge eating during which larger than reasonable quantities of food are consumed during a discrete period of time. During these episodes, people feel a lack of control, either unable to stop eating or limit the amount consumed. After binges, inappropriate compensatory behaviour to prevent weight gain is used. In the purging type of BN, self-induced vomiting, laxative misuse, diuretics or enemas are used. In the non-purging type of BN the compensatory behaviours include excessive exercise or abuse of medication. This behaviour must occur on average a minimum of once a week for three months to be diagnosed. BED has the same diagnostic criteria as BN, without the inappropriate compensatory behaviour ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "American Psychiatric Association", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "American Psychiatric Association", "publisher-place" : "Arlington, Virginia", "title" : "Diagnostic and statistical manual of mental disorders", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "(American Psychiatric Association, 2013)", "previouslyFormattedCitation" : "(American Psychiatric Association 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(American Psychiatric Association, 2013). 2.5.2 Symptoms, comorbidities, and mortality of eating disorders Of the three eating disorders, AN is considered the most dangerous. More than 10% of patients with AN will die from it in their lifetime, the highest mortality of any mental disorder ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek 2006). Short term symptoms of AN include dizziness, headaches, brain fogginess, feelings of coldness, nausea, weakness, poor sleep and blurred vision while long term issues include osteoporosis, cardiovascular disturbances, electrolyte imbalances, diabetes mellitus, thyroid disorders, gastrointestinal disorders and fertility and pregnancy problems ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.maturitas.2013.04.014", "ISSN" : "1873-4111", "PMID" : "23706279", "abstract" : "Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.", "author" : [ { "dropping-particle" : "", "family" : "Meczekalski", "given" : "Blazej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Podfigurna-Stopa", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulski", "given" : "Krzysztof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "7" ] ] }, "page" : "215-220", "publisher" : "Elsevier Ireland Ltd", "title" : "Long-term consequences of anorexia nervosa", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-2", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "(Fairburn & Harrison, 2003; Meczekalski, Podfigurna to Stopa, & Katulski, 2013)", "previouslyFormattedCitation" : "(Fairburn and Harrison 2003; Meczekalski et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn & Harrison, 2003; Meczekalski, Podfigurna to Stopa, & Katulski, 2013). Mood disorders are also common in people with AN, with estimates from 31.0 to 88.9% of patients suffering from other mental health issues. Depression is the most prevalent (40 to 45%), however bipolar affective disease, social phobia, obsessive compulsive disorder, and substance abuse are also common ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.maturitas.2013.04.014", "ISSN" : "1873-4111", "PMID" : "23706279", "abstract" : "Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.", "author" : [ { "dropping-particle" : "", "family" : "Meczekalski", "given" : "Blazej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Podfigurna-Stopa", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulski", "given" : "Krzysztof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "7" ] ] }, "page" : "215-220", "publisher" : "Elsevier Ireland Ltd", "title" : "Long-term consequences of anorexia nervosa", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Meczekalski et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Meczekalski et al. 2013). BN has a significantly lower mortality rate than AN, estimated to between 0% to 3.3% ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1176/appi.ajp.2013.12070868", "ISSN" : "1535-7228", "PMID" : "23771148", "abstract" : "OBJECTIVE Although anorexia nervosa has a high mortality rate, our understanding of the timing and predictors of mortality in eating disorders is limited. The authors investigated mortality in a long-term study of patients with eating disorders. METHOD Beginning in 1987, 246 treatment-seeking female patients with anorexia nervosa or bulimia nervosa were interviewed every 6 months for a median of 9.5 years to obtain weekly ratings of eating disorder symptoms, comorbidity, treatment participation, and psychosocial functioning. From January 2007 to December 2010 (median follow-up of 20 years), vital status was ascertained with a National Death Index search. RESULTS Sixteen deaths (6.5%) were recorded (lifetime anorexia nervosa, N=14; bulimia nervosa with no history of anorexia nervosa, N=2). The standardized mortality ratio was 4.37 (95% CI=2.4-7.3) for lifetime anorexia nervosa and 2.33 (95% CI=0.3-8.4) for bulimia nervosa with no history of anorexia nervosa. Risk of premature death among patients with lifetime anorexia nervosa peaked within the first 10 years of follow-up, resulting in a standardized mortality ratio of 7.7 (95% CI=3.7-14.2). The standardized mortality ratio varied by duration of illness and was 3.2 (95% CI=0.9-8.3) for patients with lifetime anorexia nervosa for 0 to 15 years (4/119 died), and 6.6 (95% CI=3.2-12.1) for those with lifetime anorexia nervosa for &gt;15 to 30 years (10/67 died). Multivariate predictors of mortality included alcohol abuse, low body mass index, and poor social adjustment. CONCLUSIONS These findings highlight the need for early identification and intervention and suggest that a long duration of illness, substance abuse, low weight, and poor psychosocial functioning raise the risk for mortality in anorexia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Franko", "given" : "Debra L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keshaviah", "given" : "Aparna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eddy", "given" : "Kamryn T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krishna", "given" : "Meera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "Martha C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzog", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8", "1" ] ] }, "page" : "917-925", "title" : "A longitudinal investigation of mortality in anorexia nervosa and bulimia nervosa", "type" : "article-journal", "volume" : "170" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/eat.20810", "ISSN" : "1098-108X", "PMID" : "20186717", "abstract" : "OBJECTIVE: To review recent studies describing eating disorder course and outcome. METHOD: Electronic and manual searches were conducted to identify relevant articles published since 2004. RESULTS: Twenty-six articles were identified. For anorexia nervosa (AN), most patients ascertained through outpatient settings achieved remission by 5-year follow-up. Inpatient treatment predicted poor prognosis as inpatient samples demonstrated lower remission rates. Outcome differed between bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS), including binge eating disorder (BED), for shorter follow-up durations; however, outcomes appeared similar between BN and related EDNOS by 5-year follow-up. Greater psychiatric comorbidity emerged as a significant predictor of poor prognosis in BN, whereas few prognostic indicators were identified for BED or other EDNOS. DISCUSSION: Results support optimism for most patients with eating disorders. However, more effective treatments are needed for adult AN inpatients and approximately 30% of patients with BN and related EDNOS who remain ill 10-20 years following presentation.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Tiffany a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "195-204", "title" : "Update on course and outcome in eating disorders", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel and Brown 2010; Franko et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel and Brown 2010; Franko et al. 2013). There is significant overlap of BN and AN, with 5% of people diagnosed with BN eventually developing AN and 25 to 30% of people receiving treatment for BN previously having been diagnosed with AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev.med.51.1.299", "ISSN" : "0066-4219", "PMID" : "10774466", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frank", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2000", "1" ] ] }, "page" : "299-313", "title" : "Anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2000)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2000). The medical complications of BN in comparison to AN are also generally less severe. Permanent dental erosion caused by contact with gastric acid during self-induced vomiting is one of the most common side effects, though it is also found in people with AN who purge. Electrolyte imbalances such as hypokalemia, hypochloremia, and hyponatremia, can occur as a result of repeated vomiting. These electrolyte imbalances can cause arrhythmias. Severe but rare side effects include gastric rupture or esophageal tears ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/0954026031000136839", "ISSN" : "0954-0261", "PMID" : "15276960", "abstract" : "Eating disorders rank among the most debilitating psychiatric disturbances that affect young women. Knowledge has increased in recent years about the two major eating disorders, anorexia nervosa (AN) and bulimia nervosa (BN); however, much remains unknown. This review article will provide an overview of the epidemiology, proposed risk factors and clinical features of AN, and BN, as well as current recommendations for evaluation and treatment of these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Klein", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Review of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003", "8" ] ] }, "page" : "205-216", "title" : "Eating disorders", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Klein and Walsh 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Klein and Walsh 2003). Similarly to those with AN, people with BN suffer from psychiatric comorbidities with a lifetime prevalence of between 64.1% to 84.8% ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.biopsych.2012.11.020", "ISSN" : "1873-2402", "PMID" : "23290497", "abstract" : "BACKGROUND: Little population-based data exist outside the United States on the epidemiology of binge eating disorder (BED). Cross-national BED data are presented here and compared with bulimia nervosa (BN) data in the World Health Organization (WHO) World Mental Health Surveys. METHODS: Community surveys with 24,124 respondents (ages 18+) across 14 mostly upper-middle and high-income countries assessed lifetime and 12-month DSM-IV mental disorders with the WHO Composite International Diagnostic Interview. Physical disorders were assessed with a chronic conditions checklist. RESULTS: Country-specific lifetime prevalence estimates are consistently (median; interquartile range) higher for BED (1.4%; .8-1.9%) than BN (.8%; .4-1.0%). Median age of onset is in the late teens to early 20s for both disorders but slightly younger for BN. Persistence is slightly higher for BN (6.5 years; 2.2-15.4) than BED (4.3 years; 1.0-11.7). Lifetime risk of both disorders is elevated for women and recent cohorts. Retrospective reports suggest that comorbid DSM-IV disorders predict subsequent onset of BN somewhat more strongly than BED and that BN predicts subsequent comorbid disorders somewhat more strongly than does BED. Significant comorbidities with physical conditions are due almost entirely to BN and to a somewhat lesser degree BED predicting subsequent onset of these conditions. Role impairments are similar for BN and BED. Fewer than half of lifetime BN or BED cases receive treatment. CONCLUSIONS: Binge eating disorder represents a public health problem at least equal to BN. Low treatment rates highlight the clinical importance of questioning patients about eating problems even when not included among presenting complaints.", "author" : [ { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berglund", "given" : "Patricia a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiu", "given" : "Wai Tat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deitz", "given" : "Anne C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shahly", "given" : "Victoria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aguilar-Gaxiola", "given" : "Sergio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Angermeyer", "given" : "Matthias C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benjet", "given" : "Corina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maria Haro", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovess-Masfety", "given" : "Viviane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Neill", "given" : "Siobhan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posada-Villa", "given" : "Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sasu", "given" : "Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viana", "given" : "Maria Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xavier", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "5", "1" ] ] }, "page" : "904-914", "title" : "The prevalence and correlates of binge eating disorder in the World Health Organization World Mental Health Surveys", "type" : "article-journal", "volume" : "73" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s40519-013-0020-4", "ISBN" : "4051901300", "ISSN" : "1124-4909", "author" : [ { "dropping-particle" : "", "family" : "Jaite", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoffmann", "given" : "Falk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glaeske", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachmann", "given" : "Christian J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eating and Weight Disorders", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "4", "16" ] ] }, "page" : "157-165", "title" : "Prevalence, comorbidities and outpatient treatment of anorexia and bulimia nervosa in German children and adolescents", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Jaite et al. 2013; Kessler et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Jaite et al. 2013; Kessler et al. 2013). Specific disorders include depressive disorders 40.0% to 45.8% ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s40519-013-0020-4", "ISBN" : "4051901300", "ISSN" : "1124-4909", "author" : [ { "dropping-particle" : "", "family" : "Jaite", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoffmann", "given" : "Falk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glaeske", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachmann", "given" : "Christian J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eating and Weight Disorders", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "4", "16" ] ] }, "page" : "157-165", "title" : "Prevalence, comorbidities and outpatient treatment of anorexia and bulimia nervosa in German children and adolescents", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/erv.2182", "ISSN" : "1099-0968", "PMID" : "22715021", "abstract" : "OBJECTIVE: To examine psychiatric comorbidity and factors that influence the outcome of bulimia nervosa (BN) in the general population. METHOD: Women from the nationwide birth cohorts of Finnish twins were screened for lifetime BN (N = 59) by using questionnaires and the Structured Clinical Interview for DSM-IV. We assessed psychiatric comorbidity and other prognostic factors. RESULTS: Among women with lifetime BN, the following were more common than among unaffected women: current major depressive disorder (p = 0.004), lifetime major depressive disorder (p = 0.00001) and heavy drinking (p = 0.01). Decreased likelihood of recovery was associated with a history of lifetime major depressive disorder (hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.23-0.84) and high drive for thinness at time of assessment (HR 0.96, 95% CI 0.93-0.99). DISCUSSION: Heavy drinking and depression present challenges for many women with BN. Major depressive disorder emerged as the only statistically significant prognostic factor of BN in this nationwide cohort; high drive for thinness was characteristic of the persistently ill.", "author" : [ { "dropping-particle" : "", "family" : "Keski-Rahkonen", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raevuori", "given" : "Anu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sihvola", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "Aila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Eating Disorders Review", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "3" ] ] }, "page" : "121-129", "title" : "Depression and drive for thinness are associated with persistent bulimia nervosa in the community", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Jaite et al. 2013; Keski-Rahkonen et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Jaite et al. 2013; Keski-Rahkonen et al. 2013), anxiety disorders - 15.7% ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s40519-013-0020-4", "ISBN" : "4051901300", "ISSN" : "1124-4909", "author" : [ { "dropping-particle" : "", "family" : "Jaite", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoffmann", "given" : "Falk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glaeske", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachmann", "given" : "Christian J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eating and Weight Disorders", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "4", "16" ] ] }, "page" : "157-165", "title" : "Prevalence, comorbidities and outpatient treatment of anorexia and bulimia nervosa in German children and adolescents", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Jaite et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Jaite et al. 2013), and somatoform disorders – 21.1% ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s40519-013-0020-4", "ISBN" : "4051901300", "ISSN" : "1124-4909", "author" : [ { "dropping-particle" : "", "family" : "Jaite", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoffmann", "given" : "Falk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Glaeske", "given" : "Gerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bachmann", "given" : "Christian J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eating and Weight Disorders", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "4", "16" ] ] }, "page" : "157-165", "title" : "Prevalence, comorbidities and outpatient treatment of anorexia and bulimia nervosa in German children and adolescents", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Jaite et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Jaite et al. 2013).BED is highly associated with overweight/obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1542/peds.2011-3663", "ISSN" : "1098-4275", "PMID" : "22802602", "abstract" : "OBJECTIVE: Anorexia nervosa and bulimia nervosa (BN) are rare, but eating disorders not otherwise specified (EDNOS) are relatively common among female participants. Our objective was to evaluate whether BN and subtypes of EDNOS are predictive of developing adverse outcomes. METHODS: This study comprised a prospective analysis of 8594 female participants from the ongoing Growing Up Today Study. Questionnaires were sent annually from 1996 through 2001, then biennially through 2007 and 2008. Participants who were 9 to 15 years of age in 1996 and completed at least 2 consecutive questionnaires between 1996 and 2008 were included in the analyses. Participants were classified as having BN (\u2265 weekly binge eating and purging), binge eating disorder (BED; \u2265 weekly binge eating, infrequent purging), purging disorder (PD; \u2265 weekly purging, infrequent binge eating), other EDNOS (binge eating and/or purging monthly), or nondisordered. RESULTS: BN affected \u223c1% of adolescent girls; 2% to 3% had PD and another 2% to 3% had BED. Girls with BED were almost twice as likely as their nondisordered peers to become overweight or obese (odds ratio [OR]: 1.9 [95% confidence interval: 1.0-3.5]) or develop high depressive symptoms (OR: 2.3 [95% confidence interval: 1.0-5.0]). Female participants with PD had a significantly increased risk of starting to use drugs (OR: 1.7) and starting to binge drink frequently (OR: 1.8). CONCLUSIONS: PD and BED are common and predict a range of adverse outcomes. Primary care clinicians should be made aware of these disorders, which may be underrepresented in eating disorder clinic samples. Efforts to prevent eating disorders should focus on cases of subthreshold severity.", "author" : [ { "dropping-particle" : "", "family" : "Field", "given" : "Alison E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonneville", "given" : "Kendrin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Micali", "given" : "Nadia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crosby", "given" : "Ross D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swanson", "given" : "Sonja a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laird", "given" : "Nan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solmi", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horton", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatrics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "e289-295", "title" : "Prospective association of common eating disorders and adverse outcomes", "type" : "article-journal", "volume" : "130" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/oby.2004.181", "ISSN" : "1071-7323", "PMID" : "15483209", "abstract" : "OBJECTIVE: To explore the extent to which binge eating in the absence of compensatory behaviors (BE) is associated with psychiatric and medical symptoms in men and women and to control for the independent effects of BMI. RESEARCH METHODS AND PROCEDURES: A series of regression models was applied to questionnaire data on 8045 twins, 18 to 31 years old, from a population-based Norwegian registry. RESULTS: BE was significantly associated with elevated obesity, overweight, symptoms of eating disorders, symptoms of anxiety and depression, panic attacks, depressive episodes, and reduced life satisfaction in both men and women. In women, BE was independently associated with insomnia and early menarche. In men, BE was independently associated with specific phobia, daily smoking, alcohol use, use of pain medication, impairment due to mental health, neck-shoulder, lower back, and chronic muscular pain, and impairment due to physical health. Both men and women with BE reported higher rates of psychiatric treatment. DISCUSSION: Our results indicate that there is substantial comorbidity between BE and psychiatric symptoms independently of BMI for both men and women. Medical symptoms co-occur less frequently than previously reported from treatment-seeking populations in women. Across all domains, the array of symptoms exhibited by men with BE was broader than that observed in women with BE. This observation suggests the importance of considering gender differences in future studies of psychiatric and medical morbidity, binge eating, and obesity.", "author" : [ { "dropping-particle" : "", "family" : "Reichborn-Kjennerud", "given" : "Ted", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sullivan", "given" : "Patrick F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tambs", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Jennifer R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity research", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2004", "9" ] ] }, "page" : "1445-1454", "title" : "Psychiatric and medical symptoms in binge eating in the absence of compensatory behaviors", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Reichborn-Kjennerud et al. 2004; Field et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Reichborn-Kjennerud et al. 2004; Field et al. 2012) with 2 to 25% of those seeking treatment for obesity being diagnosed with BED ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/eat.10211", "ISSN" : "0276-3478", "PMID" : "12900992", "abstract" : "OBJECTIVE: The purpose of this paper is to explore the relationship between binge eating disorder (BED) and obesity. METHODS: Recent literature relating to the etiology, risk factors, pathophysiology, and treatment of binge eating disorder was reviewed. RESULTS: The data suggest that binge eating may be a contributor to the development of obesity in susceptible individuals. Although eating disorders treatment in the absence of obesity treatment does not result in large weight losses, amelioration of binge eating does result in small weight losses and decreased weight regain over time. DISCUSSION: Our challenge in the future is to understand better the ways in which BED and obesity co-exist, and to find treatment strategies that will relieve the distress and dysfunction due to this disordered eating while enhancing appropriate weight loss or preventing further weight gain.", "author" : [ { "dropping-particle" : "", "family" : "Yanovski", "given" : "Susan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2003", "1" ] ] }, "page" : "S117-120", "title" : "Binge eating disorder and obesity in 2003: could treating an eating disorder have a positive effect on the obesity epidemic?", "type" : "article-journal", "volume" : "34 Suppl" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0003-990X", "PMID" : "10891036", "abstract" : "BACKGROUND: Little is known about the relative course and outcome of bulimia nervosa and binge eating disorder. METHODS: Two community-based cohorts were studied prospectively over a 5-year year period. One comprised 102 participants with bulimia nervosa and the other 48 participants with binge eating disorder (21% [9/42] of whom had comorbid obesity). All participants were female and aged between 16 and 35 years at recruitment. The assessments were at 15-month intervals and addressed eating disorder features, general psychiatric symptoms, and social functioning. RESULTS: Both cohorts showed marked initial improvement followed by gradual improvement thereafter. Between half and two thirds of the bulimia nervosa cohort had some form of eating disorder of clinical severity at each assessment point, although only a minority continued to meet diagnostic criteria for bulimia nervosa. Each year about a third remitted and a third relapsed. The outcome of the binge eating disorder cohort was better, with the proportion with any form of clinical eating disorder declining to 18% (7 of 40) by the 5-year follow-up. The relapse rate was low among this cohort. There was little movement of participants across the 2 diagnostic categories and few sought treatment. Both groups gained weight, with 39% of the binge eating disorder cohort (14 of 36) meeting criteria for obesity at 5-year follow-up. CONCLUSIONS: These findings suggest that, among young women in the community, bulimia nervosa and binge eating disorder have a different course and outcome. Whereas the prognosis of those with bulimia nervosa was relatively poor, the great majority of those with binge eating disorder recovered.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doll", "given" : "H a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norman", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connor", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of General Psychiatry", "id" : "ITEM-3", "issue" : "7", "issued" : { "date-parts" : [ [ "2000", "7" ] ] }, "page" : "659-665", "title" : "The natural course of bulimia nervosa and binge eating disorder in young women", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn et al. 2000; Fairburn and Harrison 2003; Yanovski 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn et al. 2000; Fairburn and Harrison 2003; Yanovski 2003). The estimated mortality of BED is 0 to 3%, however the follow up period for most studies has been relatively short which may not capture outcomes such as premature death that may occur as a result of obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.20810", "ISSN" : "1098-108X", "PMID" : "20186717", "abstract" : "OBJECTIVE: To review recent studies describing eating disorder course and outcome. METHOD: Electronic and manual searches were conducted to identify relevant articles published since 2004. RESULTS: Twenty-six articles were identified. For anorexia nervosa (AN), most patients ascertained through outpatient settings achieved remission by 5-year follow-up. Inpatient treatment predicted poor prognosis as inpatient samples demonstrated lower remission rates. Outcome differed between bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS), including binge eating disorder (BED), for shorter follow-up durations; however, outcomes appeared similar between BN and related EDNOS by 5-year follow-up. Greater psychiatric comorbidity emerged as a significant predictor of poor prognosis in BN, whereas few prognostic indicators were identified for BED or other EDNOS. DISCUSSION: Results support optimism for most patients with eating disorders. However, more effective treatments are needed for adult AN inpatients and approximately 30% of patients with BN and related EDNOS who remain ill 10-20 years following presentation.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Tiffany a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "195-204", "title" : "Update on course and outcome in eating disorders", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel and Brown 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel and Brown 2010). An estimated 63.6% of those with BED have some type of psychiatric comorbidity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hudson et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hudson et al. 2008), particularly anxiety and mood disorders ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-1", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/oby.2004.181", "ISSN" : "1071-7323", "PMID" : "15483209", "abstract" : "OBJECTIVE: To explore the extent to which binge eating in the absence of compensatory behaviors (BE) is associated with psychiatric and medical symptoms in men and women and to control for the independent effects of BMI. RESEARCH METHODS AND PROCEDURES: A series of regression models was applied to questionnaire data on 8045 twins, 18 to 31 years old, from a population-based Norwegian registry. RESULTS: BE was significantly associated with elevated obesity, overweight, symptoms of eating disorders, symptoms of anxiety and depression, panic attacks, depressive episodes, and reduced life satisfaction in both men and women. In women, BE was independently associated with insomnia and early menarche. In men, BE was independently associated with specific phobia, daily smoking, alcohol use, use of pain medication, impairment due to mental health, neck-shoulder, lower back, and chronic muscular pain, and impairment due to physical health. Both men and women with BE reported higher rates of psychiatric treatment. DISCUSSION: Our results indicate that there is substantial comorbidity between BE and psychiatric symptoms independently of BMI for both men and women. Medical symptoms co-occur less frequently than previously reported from treatment-seeking populations in women. Across all domains, the array of symptoms exhibited by men with BE was broader than that observed in women with BE. This observation suggests the importance of considering gender differences in future studies of psychiatric and medical morbidity, binge eating, and obesity.", "author" : [ { "dropping-particle" : "", "family" : "Reichborn-Kjennerud", "given" : "Ted", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sullivan", "given" : "Patrick F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tambs", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Jennifer R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity research", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2004", "9" ] ] }, "page" : "1445-1454", "title" : "Psychiatric and medical symptoms in binge eating in the absence of compensatory behaviors", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Reichborn-Kjennerud et al. 2004; Preti et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Reichborn-Kjennerud et al. 2004; Preti et al. 2009). There is evidence that some patients with BED may also develop BN, with up to 9% of patients developing BN 12 years after the diagnosis of BED ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1542/peds.2011-3663", "ISSN" : "1098-4275", "PMID" : "22802602", "abstract" : "OBJECTIVE: Anorexia nervosa and bulimia nervosa (BN) are rare, but eating disorders not otherwise specified (EDNOS) are relatively common among female participants. Our objective was to evaluate whether BN and subtypes of EDNOS are predictive of developing adverse outcomes. METHODS: This study comprised a prospective analysis of 8594 female participants from the ongoing Growing Up Today Study. Questionnaires were sent annually from 1996 through 2001, then biennially through 2007 and 2008. Participants who were 9 to 15 years of age in 1996 and completed at least 2 consecutive questionnaires between 1996 and 2008 were included in the analyses. Participants were classified as having BN (\u2265 weekly binge eating and purging), binge eating disorder (BED; \u2265 weekly binge eating, infrequent purging), purging disorder (PD; \u2265 weekly purging, infrequent binge eating), other EDNOS (binge eating and/or purging monthly), or nondisordered. RESULTS: BN affected \u223c1% of adolescent girls; 2% to 3% had PD and another 2% to 3% had BED. Girls with BED were almost twice as likely as their nondisordered peers to become overweight or obese (odds ratio [OR]: 1.9 [95% confidence interval: 1.0-3.5]) or develop high depressive symptoms (OR: 2.3 [95% confidence interval: 1.0-5.0]). Female participants with PD had a significantly increased risk of starting to use drugs (OR: 1.7) and starting to binge drink frequently (OR: 1.8). CONCLUSIONS: PD and BED are common and predict a range of adverse outcomes. Primary care clinicians should be made aware of these disorders, which may be underrepresented in eating disorder clinic samples. Efforts to prevent eating disorders should focus on cases of subthreshold severity.", "author" : [ { "dropping-particle" : "", "family" : "Field", "given" : "Alison E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonneville", "given" : "Kendrin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Micali", "given" : "Nadia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crosby", "given" : "Ross D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swanson", "given" : "Sonja a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laird", "given" : "Nan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solmi", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horton", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatrics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "e289-295", "title" : "Prospective association of common eating disorders and adverse outcomes", "type" : "article-journal", "volume" : "130" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/eat.20810", "ISSN" : "1098-108X", "PMID" : "20186717", "abstract" : "OBJECTIVE: To review recent studies describing eating disorder course and outcome. METHOD: Electronic and manual searches were conducted to identify relevant articles published since 2004. RESULTS: Twenty-six articles were identified. For anorexia nervosa (AN), most patients ascertained through outpatient settings achieved remission by 5-year follow-up. Inpatient treatment predicted poor prognosis as inpatient samples demonstrated lower remission rates. Outcome differed between bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS), including binge eating disorder (BED), for shorter follow-up durations; however, outcomes appeared similar between BN and related EDNOS by 5-year follow-up. Greater psychiatric comorbidity emerged as a significant predictor of poor prognosis in BN, whereas few prognostic indicators were identified for BED or other EDNOS. DISCUSSION: Results support optimism for most patients with eating disorders. However, more effective treatments are needed for adult AN inpatients and approximately 30% of patients with BN and related EDNOS who remain ill 10-20 years following presentation.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Tiffany a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "195-204", "title" : "Update on course and outcome in eating disorders", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel and Brown 2010; Field et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel and Brown 2010; Field et al. 2012). 2.5.3 Treatment The treatment of AN has four main components, helping patients recognize they need help and to maintain their motivation to get better after receiving help, weight restoration, addressing patients’ over evaluation of self based on shape and weight and preoccupation with eating habits, and lastly using compulsory treatment when medically necessary ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn and Harrison 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn and Harrison 2003). Whether outpatient, day-patient, or inpatient care is provided is dependent on the psychological and physiological severity of the disease. Various forms of therapy are used including family-based treatment in younger patients, and cognitive behaviour therapy (CBT) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn and Harrison 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn and Harrison 2003). An estimated 50% of people suffering from AN will recover almost fully, while 30% will continue to have symptoms intermittently throughout their life. The remaining 20% will chronically suffer from the disease, often with death from AN as the final outcome ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev.med.51.1.299", "ISSN" : "0066-4219", "PMID" : "10774466", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frank", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2000", "1" ] ] }, "page" : "299-313", "title" : "Anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2000)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2000). The treatment of BN has been relatively well studied with over 50 randomized controlled trails (RCT). The findings strongly indicate that CBT focusing on modifying the specific behaviours and ways of thinking that maintain the eating disorder is crucial with approximately 20 individual sessions over a 5 month period resulting in one third to one half of patients making a full recovery ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1017/S0033291708003942", "ISBN" : "0033291708003", "ISSN" : "0033-2917", "PMID" : "18775085", "abstract" : "BACKGROUND: Little is known about the epidemiology of bulimia nervosa outside clinical settings. We report the incidence, prevalence and outcomes of bulimia nervosa using for the first time a nationwide study design. METHOD: To assess the incidence and natural course and outcomes of DSM-IV bulimia nervosa among women from the general population, women (n=2881) from the 1975-79 birth cohorts of Finnish twins were screened for lifetime eating disorders using a two-stage procedure consisting of a questionnaire screen and the Structured Clinical Interview for DSM-IV (SCID). Clinical recovery was defined as 1-year abstinence from bingeing and purging combined with a body mass index (BMI) 19 kg/m2. RESULTS: The lifetime prevalence of DSM-IV bulimia nervosa was 2.3%; 76% of the women suffered from its purging subtype and 24% from the non-purging subtype. The incidence rate of bulimia nervosa was 300/100000 person-years at the peak age of incidence, 16-20 years, and 150/100000 at 10-24 years. The 5-year clinical recovery rate was 55.0%. Less than a third of the cases had been detected by health-care professionals; detection did not influence outcome. After clinical recovery from bulimia nervosa, the mean levels of residual psychological symptoms gradually decreased over time but many women continued to experience significantly more body image problems and psychosomatic symptoms than never-ill women. CONCLUSIONS: Few women with bulimia nervosa are recognized in health-care settings. Symptoms of bulimia are relatively long-standing, and recovery is gradual. Many clinically recovered women experience residual psychological symptoms after attaining abstinence from bingeing and purging.", "author" : [ { "dropping-particle" : "", "family" : "Keski-Rahkonen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linna", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raevuori", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sihvola", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Medicine", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5" ] ] }, "page" : "823-831", "title" : "Incidence and outcomes of bulimia nervosa: a nationwide population-based study", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1146/annurev.med.51.1.299", "ISSN" : "0066-4219", "PMID" : "10774466", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frank", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Medicine", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2000", "1" ] ] }, "page" : "299-313", "title" : "Anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2000; Fairburn and Harrison 2003; Keski-Rahkonen et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2000; Fairburn and Harrison 2003; Keski-Rahkonen et al. 2009). The results of the RCTs have also shown that antidepressant drugs have an anti-bulimic effect, decreasing the frequency of binge eating and purging. However, anti-depressant drugs are not as effective as CBT and the results are often not sustained. To date, there is no reliable evidence of predictors for successful treatment ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn and Harrison 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn and Harrison 2003). An estimated 15 to 30% of patients still meet the diagnostic criteria for BN within 5 to 10 years after diagnosis and the remainder will experience intermittent relapses over their lifetime ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev.med.51.1.299", "ISSN" : "0066-4219", "PMID" : "10774466", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frank", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2000", "1" ] ] }, "page" : "299-313", "title" : "Anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0003-990X", "PMID" : "10891036", "abstract" : "BACKGROUND: Little is known about the relative course and outcome of bulimia nervosa and binge eating disorder. METHODS: Two community-based cohorts were studied prospectively over a 5-year year period. One comprised 102 participants with bulimia nervosa and the other 48 participants with binge eating disorder (21% [9/42] of whom had comorbid obesity). All participants were female and aged between 16 and 35 years at recruitment. The assessments were at 15-month intervals and addressed eating disorder features, general psychiatric symptoms, and social functioning. RESULTS: Both cohorts showed marked initial improvement followed by gradual improvement thereafter. Between half and two thirds of the bulimia nervosa cohort had some form of eating disorder of clinical severity at each assessment point, although only a minority continued to meet diagnostic criteria for bulimia nervosa. Each year about a third remitted and a third relapsed. The outcome of the binge eating disorder cohort was better, with the proportion with any form of clinical eating disorder declining to 18% (7 of 40) by the 5-year follow-up. The relapse rate was low among this cohort. There was little movement of participants across the 2 diagnostic categories and few sought treatment. Both groups gained weight, with 39% of the binge eating disorder cohort (14 of 36) meeting criteria for obesity at 5-year follow-up. CONCLUSIONS: These findings suggest that, among young women in the community, bulimia nervosa and binge eating disorder have a different course and outcome. Whereas the prognosis of those with bulimia nervosa was relatively poor, the great majority of those with binge eating disorder recovered.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doll", "given" : "H a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norman", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connor", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of General Psychiatry", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2000", "7" ] ] }, "page" : "659-665", "title" : "The natural course of bulimia nervosa and binge eating disorder in young women", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn et al. 2000; Kaye et al. 2000)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn et al. 2000; Kaye et al. 2000). Treatments for BED focus on two aspects, weight loss and controlling binge eating ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Brownley", "given" : "Kimberly A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berkman", "given" : "Nancy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sedway", "given" : "Jan A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohr", "given" : "Kathleen N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "337-348", "title" : "Binge eating disorder treatment: A systematic review of randomized controlled trials", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Brownley et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Brownley et al. 2007). Treatment options include pharmacotherapy such as antidepressants (fluoxetine, fluvoxamine, sertraline, citalopram, imipramine, desipramine), anticonvulsants (topiramate), appetite suppressants (subutramine), fat absorption inhibitors (orlistat), behavioural interventions with CBT being the most common, though dialectical behaviour therapy has been investigated, and more unique methods such as virtual reality and self-help books ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Carter", "given" : "Jacqueline C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Counsulting and Clinical Psychology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "616-623", "title" : "Cognitive-behavioral self-help for binge eating disorder: A controlled effectiveness study", "type" : "article-journal", "volume" : "66" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Carter and Fairburn 1998)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Carter and Fairburn 1998). Combinations of drugs and behavioural interventions are also common ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Brownley", "given" : "Kimberly A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berkman", "given" : "Nancy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sedway", "given" : "Jan A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohr", "given" : "Kathleen N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "337-348", "title" : "Binge eating disorder treatment: A systematic review of randomized controlled trials", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Brownley et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Brownley et al. 2007). Overall, the evidence is limited as to which treatment options are best but the evidence suggests that as with BN, CBT in addition to pharmacotherapy options may provide the best results for controlling binge eating and reducing weight ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Brownley", "given" : "Kimberly A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berkman", "given" : "Nancy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sedway", "given" : "Jan A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohr", "given" : "Kathleen N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "337-348", "title" : "Binge eating disorder treatment: A systematic review of randomized controlled trials", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Brownley et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Brownley et al. 2007). The remission rates reported by studies are highly variable, ranging from 25 to 82% ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.20810", "ISSN" : "1098-108X", "PMID" : "20186717", "abstract" : "OBJECTIVE: To review recent studies describing eating disorder course and outcome. METHOD: Electronic and manual searches were conducted to identify relevant articles published since 2004. RESULTS: Twenty-six articles were identified. For anorexia nervosa (AN), most patients ascertained through outpatient settings achieved remission by 5-year follow-up. Inpatient treatment predicted poor prognosis as inpatient samples demonstrated lower remission rates. Outcome differed between bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS), including binge eating disorder (BED), for shorter follow-up durations; however, outcomes appeared similar between BN and related EDNOS by 5-year follow-up. Greater psychiatric comorbidity emerged as a significant predictor of poor prognosis in BN, whereas few prognostic indicators were identified for BED or other EDNOS. DISCUSSION: Results support optimism for most patients with eating disorders. However, more effective treatments are needed for adult AN inpatients and approximately 30% of patients with BN and related EDNOS who remain ill 10-20 years following presentation.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Tiffany a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "4" ] ] }, "page" : "195-204", "title" : "Update on course and outcome in eating disorders", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0003-990X", "PMID" : "10891036", "abstract" : "BACKGROUND: Little is known about the relative course and outcome of bulimia nervosa and binge eating disorder. METHODS: Two community-based cohorts were studied prospectively over a 5-year year period. One comprised 102 participants with bulimia nervosa and the other 48 participants with binge eating disorder (21% [9/42] of whom had comorbid obesity). All participants were female and aged between 16 and 35 years at recruitment. The assessments were at 15-month intervals and addressed eating disorder features, general psychiatric symptoms, and social functioning. RESULTS: Both cohorts showed marked initial improvement followed by gradual improvement thereafter. Between half and two thirds of the bulimia nervosa cohort had some form of eating disorder of clinical severity at each assessment point, although only a minority continued to meet diagnostic criteria for bulimia nervosa. Each year about a third remitted and a third relapsed. The outcome of the binge eating disorder cohort was better, with the proportion with any form of clinical eating disorder declining to 18% (7 of 40) by the 5-year follow-up. The relapse rate was low among this cohort. There was little movement of participants across the 2 diagnostic categories and few sought treatment. Both groups gained weight, with 39% of the binge eating disorder cohort (14 of 36) meeting criteria for obesity at 5-year follow-up. CONCLUSIONS: These findings suggest that, among young women in the community, bulimia nervosa and binge eating disorder have a different course and outcome. Whereas the prognosis of those with bulimia nervosa was relatively poor, the great majority of those with binge eating disorder recovered.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doll", "given" : "H a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norman", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Connor", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of General Psychiatry", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2000", "7" ] ] }, "page" : "659-665", "title" : "The natural course of bulimia nervosa and binge eating disorder in young women", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn et al. 2000; Keel and Brown 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn et al. 2000; Keel and Brown 2010), further emphasizing the need for more studies involving BED. 2.5.4 Risk factors for eating disorders Eating disorders, particularly AN and BN are considered a Western disease affecting mostly females in adolescence and early adulthood. Other general risk factors include having a family history of any type of eating disorder, depression, substance misuse, as well as either a family history of obesity or being obese in the case of BN. Life experiences including early menarche (BN), high parental expectations, sexual abuse, family dieting, criticism about one’s shape and size, and participation in activities promoting a low fat mass like distance running, swimming, dancing, and modelling increase risk ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/0954026031000136839", "ISSN" : "0954-0261", "PMID" : "15276960", "abstract" : "Eating disorders rank among the most debilitating psychiatric disturbances that affect young women. Knowledge has increased in recent years about the two major eating disorders, anorexia nervosa (AN) and bulimia nervosa (BN); however, much remains unknown. This review article will provide an overview of the epidemiology, proposed risk factors and clinical features of AN, and BN, as well as current recommendations for evaluation and treatment of these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Klein", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Review of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003", "8" ] ] }, "page" : "205-216", "title" : "Eating disorders", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Klein and Walsh 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Klein and Walsh 2003). Personality characteristics including low self-esteem, perfectionism (particularly in the case of AN), anxiety, and anxiety disorders are also risk factors for eating disorders ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn and Harrison 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn and Harrison 2003). Personal characteristics: Common personality characteristics of individuals diagnosed with AN and BN include perfectionism, obsessive-compulsiveness, neuroticism, negative emotionality, harm avoidance, low self-directedness, low cooperativeness, and traits associated with avoidant personality disorder ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2007.11.037", "ISSN" : "0031-9384", "PMID" : "18164737", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by whi\u2026", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "Walter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & behavior", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "4", "22" ] ] }, "page" : "121-135", "title" : "Neurobiology of anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "94" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.cpr.2005.04.012", "ISSN" : "0272-7358", "PMID" : "16099563", "abstract" : "Personality traits have been implicated in the onset, symptomatic expression, and maintenance of eating disorders (EDs). The present article reviews literature examining the link between personality and EDs published within the past decade, and presents a meta-analysis evaluating the prevalence of personality disorders (PDs) in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) as assessed by self-report instruments versus diagnostic interviews. AN and BN are both consistently characterized by perfectionism, obsessive-compulsiveness, neuroticism, negative emotionality, harm avoidance, low self-directedness, low cooperativeness, and traits associated with avoidant PD. Consistent differences that emerge between ED groups are high constraint and persistence and low novelty seeking in AN and high impulsivity, sensation seeking, novelty seeking, and traits associated with borderline PD in BN. The meta-analysis, which found PD rates of 0 to 58% among individuals with AN and BN, documented that self-report instruments greatly overestimate the prevalence of every PD.", "author" : [ { "dropping-particle" : "", "family" : "Cassin", "given" : "Stephanie E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ranson", "given" : "Kristin M", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Psychology Review", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "page" : "895-916", "title" : "Personality and eating disorders: a decade in review", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cassin and von Ranson 2005; Kaye 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cassin and von Ranson 2005; Kaye 2008). People with the restrictive type of AN tend to have low novelty seeking, low emotional responsiveness, decreased pleasure, decreased seeking of pleasure, and reduced social spontaneity compared to those with BN who tend to be impulsive, seek out new experiences, and have characteristics of borderline personality disorder ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2007.11.037", "ISSN" : "0031-9384", "PMID" : "18164737", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by whi\u2026", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "Walter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & behavior", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "4", "22" ] ] }, "page" : "121-135", "title" : "Neurobiology of anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "94" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.cpr.2005.04.012", "ISSN" : "0272-7358", "PMID" : "16099563", "abstract" : "Personality traits have been implicated in the onset, symptomatic expression, and maintenance of eating disorders (EDs). The present article reviews literature examining the link between personality and EDs published within the past decade, and presents a meta-analysis evaluating the prevalence of personality disorders (PDs) in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) as assessed by self-report instruments versus diagnostic interviews. AN and BN are both consistently characterized by perfectionism, obsessive-compulsiveness, neuroticism, negative emotionality, harm avoidance, low self-directedness, low cooperativeness, and traits associated with avoidant PD. Consistent differences that emerge between ED groups are high constraint and persistence and low novelty seeking in AN and high impulsivity, sensation seeking, novelty seeking, and traits associated with borderline PD in BN. The meta-analysis, which found PD rates of 0 to 58% among individuals with AN and BN, documented that self-report instruments greatly overestimate the prevalence of every PD.", "author" : [ { "dropping-particle" : "", "family" : "Cassin", "given" : "Stephanie E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ranson", "given" : "Kristin M", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Psychology Review", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "page" : "895-916", "title" : "Personality and eating disorders: a decade in review", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cassin and von Ranson 2005; Kaye 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cassin and von Ranson 2005; Kaye 2008). BED is associated with perfectionism, sensation seeking, and obsessive compulsive personality disorder, overall having many more personality characteristics in common with BN and the purging form of AN compared to the restrictive form of AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cpr.2005.04.012", "ISSN" : "0272-7358", "PMID" : "16099563", "abstract" : "Personality traits have been implicated in the onset, symptomatic expression, and maintenance of eating disorders (EDs). The present article reviews literature examining the link between personality and EDs published within the past decade, and presents a meta-analysis evaluating the prevalence of personality disorders (PDs) in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) as assessed by self-report instruments versus diagnostic interviews. AN and BN are both consistently characterized by perfectionism, obsessive-compulsiveness, neuroticism, negative emotionality, harm avoidance, low self-directedness, low cooperativeness, and traits associated with avoidant PD. Consistent differences that emerge between ED groups are high constraint and persistence and low novelty seeking in AN and high impulsivity, sensation seeking, novelty seeking, and traits associated with borderline PD in BN. The meta-analysis, which found PD rates of 0 to 58% among individuals with AN and BN, documented that self-report instruments greatly overestimate the prevalence of every PD.", "author" : [ { "dropping-particle" : "", "family" : "Cassin", "given" : "Stephanie E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ranson", "given" : "Kristin M", "non-dropping-particle" : "von", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Psychology Review", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2005", "11" ] ] }, "page" : "895-916", "title" : "Personality and eating disorders: a decade in review", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cassin and von Ranson 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cassin and von Ranson 2005). Family environment: Historically, many theories of the development of eating disorders focused on the family environment. Typically family dynamics that involve overprotective, intrusive, controlling, emotionally unresponsive, and rigid parents as well as enmeshment of parents and children, poor conflict resolution, and a lack of opportunity for children to express themselves were thought to increase eating disorder risk ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0276-3478", "PMID" : "11920974", "abstract" : "OBJECTIVE: Nonshared environmental influences are experiences that are unique to siblings reared in the same family. We review studies highlighting the importance of nonshared factors for the development of eating disorders and suggest areas for future research. METHODS: Findings from behavioral genetic studies of eating disorders as well as methodological issues are reviewed. RESULTS: Twin studies suggest that approximately 17%-46% of the variance in both anorexia nervosa (AN) and bulimia nervosa (BN) can be accounted for by nonshared environmental factors. Studies directly examining these influences are scarce, although initial data indicate that differential paternal relationships, body weight teasing, peer group experiences, and life events may account for the development of eating pathology in one sibling versus another. DISCUSSION: Additional research is needed to identify specific nonshared environmental influences on eating disorders such as differential parental and sibling treatment, disparate peer group characteristics, and differential experience of life events such as physical and sexual abuse.", "author" : [ { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wonderlich", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehoux", "given" : "Pascale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lilenfeld", "given" : "Lisa R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "3" ] ] }, "page" : "118-135", "title" : "Does environment matter? A review of nonshared environment and eating disorders", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1177/1359104509339082", "ISBN" : "1359104509339", "ISSN" : "1461-7021", "PMID" : "19759074", "abstract" : "The aim of this article is to review the clinical literature which examines the association between attachment patterns and eating disorders with a focus on anorexia nervosa, and to examine the varieties of methods and measures employed in attachment research. A literature review was carried out and the relevant articles are examined in terms of their contribution to this area. The literature indicates a number of important considerations when working with this group, including extreme separation anxiety and unresolved loss and trauma, and discusses the implications of these findings for treatment. The results also indicate conflicting evidence regarding associations between attachment style and eating disorder subgroup suggesting that severity of disorder matters more than eating disorder subtype. The different ways of investigating attachment patterns and experiences are explored in this paper. It is suggested that the attachment classification system runs the risk of reducing complex human experience to typologies and that qualitative research might help to address this problem.", "author" : [ { "dropping-particle" : "", "family" : "O'Shaughnessy", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dallos", "given" : "Rudi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Child Psychology and Psychiatry", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "10" ] ] }, "page" : "559-574", "title" : "Attachment research and eating disorders: a review of the literature", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kardum", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gra", "given" : "Asmir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hudek-Kne\u017eevi", "given" : "Jasna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Topics", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "247-263", "title" : "Evolutionary explanations of eating disorders", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Klump et al. 2002; Kardum et al. 2008; O\u2019Shaughnessy and Dallos 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Klump et al. 2002; Kardum et al. 2008; O’Shaughnessy and Dallos 2009). The development of an eating disorder was theorized to be a means for communicating avoided messages by adolescents to their parents ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/1359104509339082", "ISBN" : "1359104509339", "ISSN" : "1461-7021", "PMID" : "19759074", "abstract" : "The aim of this article is to review the clinical literature which examines the association between attachment patterns and eating disorders with a focus on anorexia nervosa, and to examine the varieties of methods and measures employed in attachment research. A literature review was carried out and the relevant articles are examined in terms of their contribution to this area. The literature indicates a number of important considerations when working with this group, including extreme separation anxiety and unresolved loss and trauma, and discusses the implications of these findings for treatment. The results also indicate conflicting evidence regarding associations between attachment style and eating disorder subgroup suggesting that severity of disorder matters more than eating disorder subtype. The different ways of investigating attachment patterns and experiences are explored in this paper. It is suggested that the attachment classification system runs the risk of reducing complex human experience to typologies and that qualitative research might help to address this problem.", "author" : [ { "dropping-particle" : "", "family" : "O'Shaughnessy", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dallos", "given" : "Rudi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Child Psychology and Psychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "10" ] ] }, "page" : "559-574", "title" : "Attachment research and eating disorders: a review of the literature", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(O\u2019Shaughnessy and Dallos 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(O’Shaughnessy and Dallos 2009). Due to the challenges in classifying, diagnosing, and studying eating disorders with the additional complication of family dynamics being difficult to study, there is limited evidence of if and how the family environment affects eating disorder risk. Broadly, a meta-analysis including 17 studies found that families which had at least one person suffering from an eating disorder reported worse family function in comparison to control families. A wide spectrum of features were used to define family functioning including cohesion, adaptability, conflict, affective expression, affective involvement, communication, task accomplishment, problem solving, achievement orientation, role performance, family hierarchy, behaviour control, adherence to values and norms, and constraining implicit family rules. The results across studies for which specific domains of family dysfunction were most relevant to all eating disorders or specific disorders were inconclusive. Some studies found significant differences between family functioning domains for different eating disorder subgroups, however none of the results were replicated across studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cpr.2013.10.005", "ISSN" : "1873-7811", "PMID" : "24321132", "abstract" : "The objectives of this review were to systematically identify and evaluate quantitative research comparing family functioning (a) in eating disorder families with control families, (b) in families with different eating disorder diagnoses (c) perceptions of different family members and (d) the relationship between family functioning and recovery. This adds to the findings of previous reviews of family functioning by including data from control families, the range of diagnoses, and focusing on recovery. Findings were considered in relation to models of family functioning. Using specific search criteria, 17 research papers were identified and evaluated. Findings indicated that eating disorder families reported worse family functioning than control families but there was little evidence for a typical pattern of family dysfunction. A consistent pattern of family dysfunction for different diagnoses was not suggested but patients consistently rated their family as more dysfunctional than one or both of their parents. With respect to outcome and recovery, those with more positive perceptions of family functioning generally had more positive outcomes, irrespective of severity of eating disorder. Conclusions were limited by inconsistent findings and methodological issues. Further research is needed into the relationship between family functioning and outcome and the assessment of family functioning beyond self-report.", "author" : [ { "dropping-particle" : "", "family" : "Holtom-Viesel", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allan", "given" : "Steven", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical psychology review", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2014", "2" ] ] }, "page" : "29-43", "publisher" : "Elsevier Ltd", "title" : "A systematic review of the literature on family functioning across all eating disorder diagnoses in comparison to control families.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Holtom-Viesel and Allan 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Holtom-Viesel and Allan 2014). A preoccupation with weight in the form of family dieting or receiving criticism about weight, eating or body shape, similarly can increase risk ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn and Harrison 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn and Harrison 2003). Weight preoccupations enforced by non-family factors, such as participating in sports that encourage thinness like dance or gymnastics or that heavily emphasize weight such as wrestling can also be damaging ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2147/CLEP.S40841", "ISSN" : "1179-1349", "PMID" : "24728136", "abstract" : "BACKGROUND: The aim of this review was to summarize the literature to date regarding the sociodemographic, environmental, and genetic correlates of eating disorders (EDs) in adults. METHOD: A keyword search was entered into Scopus (SciVerse, Elsevier) to identify relevant articles published in English up until June 2013. Articles were assessed against a range of a priori inclusion and exclusion criteria. RESULTS: A total of 149 full-text articles were found to be eligible for the review and included 86 articles with data on sociodemographic correlates, 57 on environmental correlates, and 13 on genetic correlates. Female sex, younger age, sexual and physical abuse, participation in esthetic or weight-oriented sports, and heritability were found to be most consistently associated with higher ED prevalence and incidence. Conversely, ethnicity, socioeconomic status, education, and urbanicity did not appear to have strong associations with ED epidemiology. CONCLUSION: More community-based research, with an equal representation of males, needs to be conducted to confirm the current findings and provide evidence for emerging factors that may be related to EDs.", "author" : [ { "dropping-particle" : "", "family" : "Mitchison", "given" : "Deborah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hay", "given" : "Phillipa J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Epidemiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "89-97", "title" : "The epidemiology of eating disorders: genetic, environmental, and societal factors", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mitchison and Hay 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mitchison and Hay 2014). Though not always related to the family, childhood trauma has been found to increase the risk of developing an eating disorder, particularly if the abuse was sexual or physical in nature ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.10008", "author" : [ { "dropping-particle" : "", "family" : "Smolak", "given" : "Linda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murnen", "given" : "Sarah K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "559-574", "title" : "A meta-analytic examination of the relationship between child sexual abuse and eating disorders", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.2147/CLEP.S40841", "ISSN" : "1179-1349", "PMID" : "24728136", "abstract" : "BACKGROUND: The aim of this review was to summarize the literature to date regarding the sociodemographic, environmental, and genetic correlates of eating disorders (EDs) in adults. METHOD: A keyword search was entered into Scopus (SciVerse, Elsevier) to identify relevant articles published in English up until June 2013. Articles were assessed against a range of a priori inclusion and exclusion criteria. RESULTS: A total of 149 full-text articles were found to be eligible for the review and included 86 articles with data on sociodemographic correlates, 57 on environmental correlates, and 13 on genetic correlates. Female sex, younger age, sexual and physical abuse, participation in esthetic or weight-oriented sports, and heritability were found to be most consistently associated with higher ED prevalence and incidence. Conversely, ethnicity, socioeconomic status, education, and urbanicity did not appear to have strong associations with ED epidemiology. CONCLUSION: More community-based research, with an equal representation of males, needs to be conducted to confirm the current findings and provide evidence for emerging factors that may be related to EDs.", "author" : [ { "dropping-particle" : "", "family" : "Mitchison", "given" : "Deborah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hay", "given" : "Phillipa J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Epidemiology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "89-97", "title" : "The epidemiology of eating disorders: genetic, environmental, and societal factors", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Smolak and Murnen 2002; Mitchison and Hay 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Smolak and Murnen 2002; Mitchison and Hay 2014). Gender: AN is most prevalent in females, with a ratio of 10-20 females diagnosed for each male and an overall lifetime prevalence of 0.3 to 3.0% for females and 0.24 to 0.30% for males in Western countries ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.maturitas.2013.04.014", "ISSN" : "1873-4111", "PMID" : "23706279", "abstract" : "Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.", "author" : [ { "dropping-particle" : "", "family" : "Meczekalski", "given" : "Blazej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Podfigurna-Stopa", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulski", "given" : "Krzysztof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "7" ] ] }, "page" : "215-220", "publisher" : "Elsevier Ireland Ltd", "title" : "Long-term consequences of anorexia nervosa", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-4", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/eat.parative", "author" : [ { "dropping-particle" : "", "family" : "Marques", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chih-nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chosak", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belo Diniz", "given" : "Juliana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "412-420", "title" : "Comparative prevalence, correlates of impairment, and service utilization for eating disorders across U.S. ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.appet.2013.01.005", "ISSN" : "1095-8304", "PMID" : "23348361", "abstract" : "During the last 25 years, the careful examination of the eating behavior of individuals with eating disorders has provided critical insights into the nature of these disorders. Crucially, studies investigating components of different eating behaviors have documented that Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED) are characterized by objective disturbances in eating patterns that are significantly different than behaviors exhibited by individuals who do not have these eating disorders. The detailed description of the disturbances in eating behavior has helped to identify diagnostic criteria associated with each disorder, and has led to important hypotheses about the underlying pathophysiology. These advances in understanding have provided, and continue to provide, a foundation for translational research and for the development of novel treatment interventions. This review is based on a presentation given by B. Timothy Walsh, M.D. at the 40th anniversary symposium of the Columbia University Appetite talks outlining the evolution of the discovery of the characteristic eating disturbances seen with each disorder.", "author" : [ { "dropping-particle" : "", "family" : "Heaner", "given" : "Martica K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Appetite", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "185-188", "publisher" : "Elsevier Ltd", "title" : "A history of the identification of the characteristics eating disturbances of bulimia nervosa, binge eating disorders and anorexia nervosa", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-7", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-8", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-10", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Favaro et al. 2003; Hoek and van Hoeken 2003; Currin et al. 2005; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Favaro et al. 2003; Hoek and van Hoeken 2003; Currin et al. 2005; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013). BN is similarly more prevalent in females with approximately 0.88 to 4.6% of females suffering from the disease in Western countries ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11920-012-0282-y", "ISSN" : "1535-1645", "PMID" : "22644309", "abstract" : "Eating disorders are relatively rare among the general population. This review discusses the literature on the incidence, prevalence and mortality rates of eating disorders. We searched online Medline/Pubmed, Embase and PsycINFO databases for articles published in English using several keyterms relating to eating disorders and epidemiology. Anorexia nervosa is relatively common among young women. While the overall incidence rate remained stable over the past decades, there has been an increase in the high risk-group of 15-19 year old girls. It is unclear whether this reflects earlier detection of anorexia nervosa cases or an earlier age at onset. The occurrence of bulimia nervosa might have decreased since the early nineties of the last century. All eating disorders have an elevated mortality risk; anorexia nervosa the most striking. Compared with the other eating disorders, binge eating disorder is more common among males and older individuals.", "author" : [ { "dropping-particle" : "", "family" : "Smink", "given" : "Fr\u00e9d\u00e9rique R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Psychiatry Reports", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "406-414", "title" : "Epidemiology of eating disorders: incidence, prevalence and mortality rates", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1017/S0033291708003942", "ISBN" : "0033291708003", "ISSN" : "0033-2917", "PMID" : "18775085", "abstract" : "BACKGROUND: Little is known about the epidemiology of bulimia nervosa outside clinical settings. We report the incidence, prevalence and outcomes of bulimia nervosa using for the first time a nationwide study design. METHOD: To assess the incidence and natural course and outcomes of DSM-IV bulimia nervosa among women from the general population, women (n=2881) from the 1975-79 birth cohorts of Finnish twins were screened for lifetime eating disorders using a two-stage procedure consisting of a questionnaire screen and the Structured Clinical Interview for DSM-IV (SCID). Clinical recovery was defined as 1-year abstinence from bingeing and purging combined with a body mass index (BMI) 19 kg/m2. RESULTS: The lifetime prevalence of DSM-IV bulimia nervosa was 2.3%; 76% of the women suffered from its purging subtype and 24% from the non-purging subtype. The incidence rate of bulimia nervosa was 300/100000 person-years at the peak age of incidence, 16-20 years, and 150/100000 at 10-24 years. The 5-year clinical recovery rate was 55.0%. Less than a third of the cases had been detected by health-care professionals; detection did not influence outcome. After clinical recovery from bulimia nervosa, the mean levels of residual psychological symptoms gradually decreased over time but many women continued to experience significantly more body image problems and psychosomatic symptoms than never-ill women. CONCLUSIONS: Few women with bulimia nervosa are recognized in health-care settings. Symptoms of bulimia are relatively long-standing, and recovery is gradual. Many clinically recovered women experience residual psychological symptoms after attaining abstinence from bingeing and purging.", "author" : [ { "dropping-particle" : "", "family" : "Keski-Rahkonen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linna", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raevuori", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sihvola", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Medicine", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5" ] ] }, "page" : "823-831", "title" : "Incidence and outcomes of bulimia nervosa: a nationwide population-based study", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-6", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-7", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-8", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Favaro et al. 2003; Hoek and van Hoeken 2003; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Keski-Rahkonen et al. 2009; Preti et al. 2009; Smink et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Favaro et al. 2003; Hoek and van Hoeken 2003; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Keski-Rahkonen et al. 2009; Preti et al. 2009; Smink et al. 2012) compared to 0.10 to 1.5% of males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11920-012-0282-y", "ISSN" : "1535-1645", "PMID" : "22644309", "abstract" : "Eating disorders are relatively rare among the general population. This review discusses the literature on the incidence, prevalence and mortality rates of eating disorders. We searched online Medline/Pubmed, Embase and PsycINFO databases for articles published in English using several keyterms relating to eating disorders and epidemiology. Anorexia nervosa is relatively common among young women. While the overall incidence rate remained stable over the past decades, there has been an increase in the high risk-group of 15-19 year old girls. It is unclear whether this reflects earlier detection of anorexia nervosa cases or an earlier age at onset. The occurrence of bulimia nervosa might have decreased since the early nineties of the last century. All eating disorders have an elevated mortality risk; anorexia nervosa the most striking. Compared with the other eating disorders, binge eating disorder is more common among males and older individuals.", "author" : [ { "dropping-particle" : "", "family" : "Smink", "given" : "Fr\u00e9d\u00e9rique R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Psychiatry Reports", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "406-414", "title" : "Epidemiology of eating disorders: incidence, prevalence and mortality rates", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-3", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hudson et al. 2008; Preti et al. 2009; Smink et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hudson et al. 2008; Preti et al. 2009; Smink et al. 2012). Compared to AN and BN, BED is more equally distributed between the genders. The lifetime prevalence is estimated to be between 2.5 to 3.5% for females and 1.5 to 2.0% for males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Spitzer", "given" : "R.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devlin", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasin", "given" : "Deborah S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stunkard", "given" : "A.J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wadden", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Susan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Agras", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nonas", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "191-204", "title" : "Binge eating disorder: A multisite field trial of the diagnostic criteria", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Spitzer", "given" : "R.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Susan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wadden", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "M D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stunkard", "given" : "A.J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devlin", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasin", "given" : "Deborah S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horne", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "137-154", "title" : "Binge eating disorder: Its further validation in a multi-site study.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0276-3478", "PMID" : "10191993", "abstract" : "OBJECTIVE: The authors investigated the prevalence of binge eating behavior in a general female Austrian population. METHOD: A random sample of 1,000 women (age range 15a to 85a) was interviewed by dieticians over the phone. Some screening instruments were used to detect binge eating behavior. RESULTS: Of the entire sample, 122 met the diagnostic criteria for binge eating, 84 for binge eating syndrome, and 33 for binge eating disorder (BED). The point prevalence of bulimia nervosa was 1.5%. Women with binge eating episodes carried out more frequently one or more diets within the previous year, and more frequently exhibited a restrained eating behavior than did women without binge eating behavior. Underweight women more often met the diagnostic criteria for bulimia nervosa nonpurging type than did normal weight, overweight, and obese women, while overweight and obese women more frequently met the diagnostic criteria for BED. DISCUSSION: Our findings indicate that binge eating appears to be a fairly common behavior in women. Dieting, chronic restrained eating, and excessive exercise may be important triggers for BED and bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Kinzl", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Traweger", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trefalt", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangweth", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biebl", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "4" ] ] }, "page" : "287-292", "title" : "Binge eating disorder in females: a population-based investigation", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0276-3478", "PMID" : "9561427", "abstract" : "OBJECTIVE: The study aims were to evaluate the prevalence and distribution of respective eating disorder behaviors (DSM-IV criteria) in a representative community-based sample. METHOD: Data were obtained from 3,001 interviews of a randomly selected sample of 4,200 individuals' (age > 15 years) households in South Australia. RESULTS: Ninety-six (3.2%) of respondents had regular current episodes of binge eating, 48 (1.6%) regularly fasted or used strict dieting, 24 (0.8%) purged. An estimated 8 (0.3%) had bulimia nervosa and 30 (1%) had binge eating disorder. Binge eating and dieting were most common in people who were in their early to mid thirties. Dieting and purging, but not regular binge eating, were more common in women than in men. Purging was most common in the 35-44 year age range. The only behavior significantly associated with (increased) weight was binge eating. Unmarried subjects were less likely to diet than married subjects. No significant differences in rates of these behaviors were found for household income. DISCUSSION: Problematic eating disorder behaviors in older women and in men were more common than expected and merit further clinical and research attention.", "author" : [ { "dropping-particle" : "", "family" : "Hay", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-5", "issue" : "4", "issued" : { "date-parts" : [ [ "1998", "5" ] ] }, "page" : "371-382", "title" : "The epidemiology of eating disorder behaviors: an Australian community-based survey", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Spitzer et al. 1992, 1993; Hay 1998; Kinzl et al. 1999; Hudson et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Spitzer et al. 1992, 1993; Hay 1998; Kinzl et al. 1999; Hudson et al. 2008). A general estimate is that up to 25% people with BED are male ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn and Harrison 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn and Harrison 2003).Age: AN and BN both predominantly affect young people, though AN has a slightly earlier age of onset compared to BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(03)12378-1", "ISSN" : "0140-6736", "PMID" : "12573387", "abstract" : "Eating disorders are an important cause of physical and psychosocial morbidity in adolescent girls and young adult women. They are much less frequent in men. Eating disorders are divided into three diagnostic categories: anorexia nervosa, bulimia nervosa, and the atypical eating disorders. However, the disorders have many features in common and patients frequently move between them, so for the purposes of this Seminar we have adopted a transdiagnostic perspective. The cause of eating disorders is complex and badly understood. There is a genetic predisposition, and certain specific environmental risk factors have been implicated. Research into treatment has focused on bulimia nervosa, and evidence-based management of this disorder is possible. A specific form of cognitive behaviour therapy is the most effective treatment, although few patients seem to receive it in practice. Treatment of anorexia nervosa and atypical eating disorders has received remarkably little research attention.", "author" : [ { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrison", "given" : "Paul J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9355", "issued" : { "date-parts" : [ [ "2003", "2", "1" ] ] }, "page" : "407-416", "title" : "Eating disorders", "type" : "article-journal", "volume" : "361" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fairburn and Harrison 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fairburn and Harrison 2003). The peak incidence of AN is between the years of 10 and 19 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "Van", "family" : "Son", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartelds", "given" : "Aad I M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "565-569", "title" : "Time trends in the incidence of eating disorders: A primary care study in the Netherlands", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fornari", "given" : "Victor M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Devra L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sunday", "given" : "Suzanne R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandberg", "given" : "David E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Ii-lun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandel", "given" : "Francine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halmi", "given" : "Katherine A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Jack L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "North", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hospitalcornell", "given" : "Universiy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Compr Psychiatry", "id" : "ITEM-5", "issue" : "6", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "450-456", "title" : "Seasonal patterns in eating disorder subgroups", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1176/appi.ajp.2013.12070868", "ISSN" : "1535-7228", "PMID" : "23771148", "abstract" : "OBJECTIVE Although anorexia nervosa has a high mortality rate, our understanding of the timing and predictors of mortality in eating disorders is limited. The authors investigated mortality in a long-term study of patients with eating disorders. METHOD Beginning in 1987, 246 treatment-seeking female patients with anorexia nervosa or bulimia nervosa were interviewed every 6 months for a median of 9.5 years to obtain weekly ratings of eating disorder symptoms, comorbidity, treatment participation, and psychosocial functioning. From January 2007 to December 2010 (median follow-up of 20 years), vital status was ascertained with a National Death Index search. RESULTS Sixteen deaths (6.5%) were recorded (lifetime anorexia nervosa, N=14; bulimia nervosa with no history of anorexia nervosa, N=2). The standardized mortality ratio was 4.37 (95% CI=2.4-7.3) for lifetime anorexia nervosa and 2.33 (95% CI=0.3-8.4) for bulimia nervosa with no history of anorexia nervosa. Risk of premature death among patients with lifetime anorexia nervosa peaked within the first 10 years of follow-up, resulting in a standardized mortality ratio of 7.7 (95% CI=3.7-14.2). The standardized mortality ratio varied by duration of illness and was 3.2 (95% CI=0.9-8.3) for patients with lifetime anorexia nervosa for 0 to 15 years (4/119 died), and 6.6 (95% CI=3.2-12.1) for those with lifetime anorexia nervosa for &gt;15 to 30 years (10/67 died). Multivariate predictors of mortality included alcohol abuse, low body mass index, and poor social adjustment. CONCLUSIONS These findings highlight the need for early identification and intervention and suggest that a long duration of illness, substance abuse, low weight, and poor psychosocial functioning raise the risk for mortality in anorexia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Franko", "given" : "Debra L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keshaviah", "given" : "Aparna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eddy", "given" : "Kamryn T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krishna", "given" : "Meera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "Martha C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzog", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-6", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8", "1" ] ] }, "page" : "917-925", "title" : "A longitudinal investigation of mortality in anorexia nervosa and bulimia nervosa", "type" : "article-journal", "volume" : "170" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1016/j.biopsych.2012.11.020", "ISSN" : "1873-2402", "PMID" : "23290497", "abstract" : "BACKGROUND: Little population-based data exist outside the United States on the epidemiology of binge eating disorder (BED). Cross-national BED data are presented here and compared with bulimia nervosa (BN) data in the World Health Organization (WHO) World Mental Health Surveys. METHODS: Community surveys with 24,124 respondents (ages 18+) across 14 mostly upper-middle and high-income countries assessed lifetime and 12-month DSM-IV mental disorders with the WHO Composite International Diagnostic Interview. Physical disorders were assessed with a chronic conditions checklist. RESULTS: Country-specific lifetime prevalence estimates are consistently (median; interquartile range) higher for BED (1.4%; .8-1.9%) than BN (.8%; .4-1.0%). Median age of onset is in the late teens to early 20s for both disorders but slightly younger for BN. Persistence is slightly higher for BN (6.5 years; 2.2-15.4) than BED (4.3 years; 1.0-11.7). Lifetime risk of both disorders is elevated for women and recent cohorts. Retrospective reports suggest that comorbid DSM-IV disorders predict subsequent onset of BN somewhat more strongly than BED and that BN predicts subsequent comorbid disorders somewhat more strongly than does BED. Significant comorbidities with physical conditions are due almost entirely to BN and to a somewhat lesser degree BED predicting subsequent onset of these conditions. Role impairments are similar for BN and BED. Fewer than half of lifetime BN or BED cases receive treatment. CONCLUSIONS: Binge eating disorder represents a public health problem at least equal to BN. Low treatment rates highlight the clinical importance of questioning patients about eating problems even when not included among presenting complaints.", "author" : [ { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berglund", "given" : "Patricia a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chiu", "given" : "Wai Tat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deitz", "given" : "Anne C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shahly", "given" : "Victoria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aguilar-Gaxiola", "given" : "Sergio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Angermeyer", "given" : "Matthias C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benjet", "given" : "Corina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maria Haro", "given" : "Josep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovess-Masfety", "given" : "Viviane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Neill", "given" : "Siobhan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Posada-Villa", "given" : "Jose", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sasu", "given" : "Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viana", "given" : "Maria Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xavier", "given" : "Miguel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-7", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "5", "1" ] ] }, "page" : "904-914", "title" : "The prevalence and correlates of binge eating disorder in the World Health Organization World Mental Health Surveys", "type" : "article-journal", "volume" : "73" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-8", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fornari et al. 1994; Favaro et al. 2003; Hoek and van Hoeken 2003; Currin et al. 2005; Son et al. 2006; Wade et al. 2006; Franko et al. 2013; Kessler et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fornari et al. 1994; Favaro et al. 2003; Hoek and van Hoeken 2003; Currin et al. 2005; Son et al. 2006; Wade et al. 2006; Franko et al. 2013; Kessler et al. 2013) with an estimated 40% of all cases of AN occurring in those 15 to 19 years of age ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek and van Hoeken 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek and van Hoeken 2003). For BN, there is greater variability in the estimates of peak incidence, which in part could be because of the use of different age cut off points as well as the relatively recent changes in diagnostic criteria. The peak incidence is estimated to be as low as 10 to 20 years of age ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1017/S0033291708003942", "ISBN" : "0033291708003", "ISSN" : "0033-2917", "PMID" : "18775085", "abstract" : "BACKGROUND: Little is known about the epidemiology of bulimia nervosa outside clinical settings. We report the incidence, prevalence and outcomes of bulimia nervosa using for the first time a nationwide study design. METHOD: To assess the incidence and natural course and outcomes of DSM-IV bulimia nervosa among women from the general population, women (n=2881) from the 1975-79 birth cohorts of Finnish twins were screened for lifetime eating disorders using a two-stage procedure consisting of a questionnaire screen and the Structured Clinical Interview for DSM-IV (SCID). Clinical recovery was defined as 1-year abstinence from bingeing and purging combined with a body mass index (BMI) 19 kg/m2. RESULTS: The lifetime prevalence of DSM-IV bulimia nervosa was 2.3%; 76% of the women suffered from its purging subtype and 24% from the non-purging subtype. The incidence rate of bulimia nervosa was 300/100000 person-years at the peak age of incidence, 16-20 years, and 150/100000 at 10-24 years. The 5-year clinical recovery rate was 55.0%. Less than a third of the cases had been detected by health-care professionals; detection did not influence outcome. After clinical recovery from bulimia nervosa, the mean levels of residual psychological symptoms gradually decreased over time but many women continued to experience significantly more body image problems and psychosomatic symptoms than never-ill women. CONCLUSIONS: Few women with bulimia nervosa are recognized in health-care settings. Symptoms of bulimia are relatively long-standing, and recovery is gradual. Many clinically recovered women experience residual psychological symptoms after attaining abstinence from bingeing and purging.", "author" : [ { "dropping-particle" : "", "family" : "Keski-Rahkonen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linna", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raevuori", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sihvola", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Medicine", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5" ] ] }, "page" : "823-831", "title" : "Incidence and outcomes of bulimia nervosa: a nationwide population-based study", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Currin et al. 2005; Keski-Rahkonen et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Currin et al. 2005; Keski-Rahkonen et al. 2009), or as high as 25 to 29 years ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "Van", "family" : "Son", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartelds", "given" : "Aad I M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "565-569", "title" : "Time trends in the incidence of eating disorders: A primary care study in the Netherlands", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Son et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Son et al. 2006) with other estimates falling in between those ranges ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0276-3478", "PMID" : "10191993", "abstract" : "OBJECTIVE: The authors investigated the prevalence of binge eating behavior in a general female Austrian population. METHOD: A random sample of 1,000 women (age range 15a to 85a) was interviewed by dieticians over the phone. Some screening instruments were used to detect binge eating behavior. RESULTS: Of the entire sample, 122 met the diagnostic criteria for binge eating, 84 for binge eating syndrome, and 33 for binge eating disorder (BED). The point prevalence of bulimia nervosa was 1.5%. Women with binge eating episodes carried out more frequently one or more diets within the previous year, and more frequently exhibited a restrained eating behavior than did women without binge eating behavior. Underweight women more often met the diagnostic criteria for bulimia nervosa nonpurging type than did normal weight, overweight, and obese women, while overweight and obese women more frequently met the diagnostic criteria for BED. DISCUSSION: Our findings indicate that binge eating appears to be a fairly common behavior in women. Dieting, chronic restrained eating, and excessive exercise may be important triggers for BED and bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Kinzl", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Traweger", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trefalt", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangweth", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biebl", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "4" ] ] }, "page" : "287-292", "title" : "Binge eating disorder in females: a population-based investigation", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-3", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kinzl et al. 1999; Hoek and van Hoeken 2003; Preti et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kinzl et al. 1999; Hoek and van Hoeken 2003; Preti et al. 2009).The average age of onset provides more specific estimates, 20.0 years of age for BN purging type, 19.0 years for BN non-purging type ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wade et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wade et al. 2006) and between 17.0 and 19.7 years for both types combined ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fornari", "given" : "Victor M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Devra L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sunday", "given" : "Suzanne R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandberg", "given" : "David E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Ii-lun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandel", "given" : "Francine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halmi", "given" : "Katherine A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Jack L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "North", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hospitalcornell", "given" : "Universiy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Compr Psychiatry", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "450-456", "title" : "Seasonal patterns in eating disorder subgroups", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fornari et al. 1994; Favaro et al. 2003; Hudson et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fornari et al. 1994; Favaro et al. 2003; Hudson et al. 2008). There are currently no reliable estimates of peak incidence for BED. However, three studies have found that the incidence of the disease is relatively equally distributed across the lifespan. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0276-3478", "PMID" : "10191993", "abstract" : "OBJECTIVE: The authors investigated the prevalence of binge eating behavior in a general female Austrian population. METHOD: A random sample of 1,000 women (age range 15a to 85a) was interviewed by dieticians over the phone. Some screening instruments were used to detect binge eating behavior. RESULTS: Of the entire sample, 122 met the diagnostic criteria for binge eating, 84 for binge eating syndrome, and 33 for binge eating disorder (BED). The point prevalence of bulimia nervosa was 1.5%. Women with binge eating episodes carried out more frequently one or more diets within the previous year, and more frequently exhibited a restrained eating behavior than did women without binge eating behavior. Underweight women more often met the diagnostic criteria for bulimia nervosa nonpurging type than did normal weight, overweight, and obese women, while overweight and obese women more frequently met the diagnostic criteria for BED. DISCUSSION: Our findings indicate that binge eating appears to be a fairly common behavior in women. Dieting, chronic restrained eating, and excessive exercise may be important triggers for BED and bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Kinzl", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Traweger", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trefalt", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangweth", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biebl", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "4" ] ] }, "page" : "287-292", "title" : "Binge eating disorder in females: a population-based investigation", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Grucza", "given" : "Richard A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Przybeck", "given" : "T R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cloninger", "given" : "C R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Comprehensive Psychiatry", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "124-131", "title" : "Prevalence and correlates of binge eating disorder in a community sample", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woo", "given" : "Meghan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Zhun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torres", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Xiao-li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striegel-moore", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "S15-S21", "title" : "Prevalence and correlates of eating disorders in Latinos in the United States", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kinzl et al. 1999; Alegria et al. 2007; Grucza et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kinzl et al. 1999; Alegria et al. 2007; Grucza et al. 2007). Point estimates for the age of onset of BED range from 18.3 years ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Favaro et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Favaro et al. 2003) to 25.4 years ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/eat.1112", "author" : [ { "dropping-particle" : "", "family" : "Barry", "given" : "Declan T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grilo", "given" : "Carlos M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masheb", "given" : "Robin M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Interrnational Journal of Eating Disorders", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2002" ] ] }, "page" : "63-70", "title" : "Gender differences in patients with binge eating disorder", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Barry et al. 2002; Wade et al. 2006; Hudson et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Barry et al. 2002; Wade et al. 2006; Hudson et al. 2008). In a study consisting of participants from six European countries, it was found that while there were no new cases of AN diagnosed after 20 years of age and only a limited number of cases of BN, BED continued to be regularly diagnosed in people above the age of 40 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-1", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Preti et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Preti et al. 2009). A possible explanation for the differences in peak incidence estimates for BED is provided by ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0276-3478", "PMID" : "8986518", "abstract" : "OBJECTIVE: In examining individuals with binge eating disorder (BED), we aimed to determine whether their binge eating preceded their first diet or their first diet preceded their binge eating, the age of their first diet, the age of their first binge, and the age when they met DSM-IV criteria for BED. Additionally, we aimed to identify psychological factors that may distinguish the two groups. METHODS: Eighty-seven individuals with BED (19 men and 68 women) were administered the Eating Disorders Examination, the Structured Clinical Interview for DSM-III-R, and several other measures of psychological functioning and psychiatric disturbance. RESULTS: Forty-five percent of the subjects reported that dieting preceded their first binge episode (dietfirst) and 55% reported that binge eating preceded their first diet (bingefirst). There were no significant differences in current eating disturbance, body mass index (BMI), or age for these two groups, but they differed on the age of the first episode of binge eating and the age when binging met BED criteria. The group reporting having binged first had a younger age of onset of binge eating and a younger age at which binge eating met diagnostic criteria than the dietfirst group. The bingefirst group also had a history of more psychiatric problems and were more likely to have an Axis II personality disorder. DISCUSSION: Age of onset of the first binge and BED is markedly different depending on whether an individual began dieting or binging first. These findings suggest that there may be important etiological differences between individuals who binge first and those who diet first. Moreover, individuals who binge first may be at greater risk for psychiatric disturbance.", "author" : [ { "dropping-particle" : "", "family" : "Spurrell", "given" : "E B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilfley", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanofsky", "given" : "M B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brownell", "given" : "K D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1997", "1" ] ] }, "page" : "55-65", "title" : "Age of onset for binge eating: are there different pathways to binge eating?", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Spurrell et al. (1997)", "previouslyFormattedCitation" : "(Spurrell et al. 1997)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Spurrell et al. (1997) who found that there was a statistically significant difference in the age that individuals first met the criteria for BED between those who starting binging first versus those who started dieting first. In the binge first group, the average age of meeting the criteria for BED was 18.81 (+/- 10.74) years and in the diet first group, the average age of meeting the criteria for BED was 33.20 (+/-11.95) years. Similar results were found in a study by ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0307-0565", "PMID" : "10805495", "abstract" : "OBJECTIVE: To examine the potential significance of the sequence of the onset of dieting and binge eating in binge eating disorder (BED). DESIGN: BED patients were interviewed and completed a battery of psychometrically well-established measures of current eating behaviors, eating disorder psychopathology, and associated psychological functioning. SUBJECTS: Participants were 98 consecutive outpatients with BED evaluated for a clinical trial. MEASURES: Interview data, self-report measures and measured body weight were examined. RESULTS: Participants who reported that dieting preceded binge eating (DIETfirst, 65%) were compared to those who reported that binge eating preceded their first diet (BINGEfirst, 35%). The study groups did not differ in demography, current or highest body mass index, current eating behaviors or psychopathology, or psychological functioning. The two groups did not differ in age of first diet; however, the BINGEfirst group was significantly younger when first overweight, at onset of binge eating, and at onset of BED diagnosis. The BINGEfirst group reported a higher frequency of being teased about their weight. CONCLUSIONS: A substantial subgroup of BED patients report that binge eating preceded their first diet. This finding, which replicates previous reports for BED and appears higher than that generally reported for bulimia nervosa, may have implication for etiologic models of binge eating.", "author" : [ { "dropping-particle" : "", "family" : "Grilo", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masheb", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2000", "4" ] ] }, "page" : "404-409", "title" : "Onset of dieting vs binge eating in outpatients with binge eating disorder", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Grilo and Masheb (2000)", "previouslyFormattedCitation" : "(Grilo and Masheb 2000)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Grilo and Masheb (2000).Time Trends: A study conducted in six European countries found an inverse association between cohort (age at interview) and lifetime risk of eating disorders, with the younger cohort (18 to 29 years) having an odds ratio of 7.9 (3.89 to 16.20) of developing any eating disorder in their lifetime compared to the 45 years and older age category ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-1", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Preti et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Preti et al. 2009). This relationship was true for all subcategories of eating disorders with the lowest odds ratio for BN (4.1), and the highest for AN (14.5). A meta-analysis of the diagnosis of AN and BN globally with a focus on Westernized countries found a correlation of 0.35 for the association between time and the increase of AN and a correlation of 0.89 for BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel and Klump 2003). A small review by ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Hoek and van Hoeken (2003)", "previouslyFormattedCitation" : "(Hoek and van Hoeken 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Hoek and van Hoeken (2003) supports that there has been an overall increase in the incidence of BN in the United States, Netherlands, and United Kingdom from the early 1980s to the early 1990s as well as an upwards trend since the 1950s of the incidence in AN, specifically in 15 to 24 year old females, though the same increase in incidence was not found in males and females over 25 years of age.Studies published after the reviews have provided conflicting evidence of if the incidence of eating disorders are increasing over time. A population based sample (n=3001 in 1995, and 3047 in 2005) from metropolitan South Australia, found that there was a 2.4 times greater risk for being diagnosed with BED in 2005 compared to 1995 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pone.0001541", "ISSN" : "1932-6203", "PMID" : "18253489", "abstract" : "BACKGROUND: Evidence for an increase in the prevalence of eating disorders is inconsistent. Our aim was to determine change in the population point prevalence of eating disorder behaviors over a 10-year period. METHODOLOGY/PRINCIPAL FINDINGS: Eating disorder behaviors were assessed in consecutive general population surveys of men and women conducted in 1995 (n = 3001, 72% respondents) and 2005 (n = 3047, 63.1% respondents). Participants were randomly sampled from households in rural and metropolitan South Australia. There was a significant (all p<0.01) and over two-fold increase in the prevalence of binge eating, purging (self-induced vomiting and/or laxative or diuretic misuse) and strict dieting or fasting for weight or shape control among both genders. The most common diagnosis in 2005 was either binge eating disorder or other \"eating disorders not otherwise specified\" (EDNOS; n = 119, 4.2%). CONCLUSIONS/SIGNIFICANCE: In this population sample the point prevalence of eating disorder behaviors increased over the past decade. Cases of anorexia nervosa and bulimia nervosa, as currently defined, remain uncommon.", "author" : [ { "dropping-particle" : "", "family" : "Hay", "given" : "Phillipa J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mond", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buttner", "given" : "Petra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Darby", "given" : "Anita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PloS one", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008", "1" ] ] }, "page" : "e1541", "title" : "Eating disorder behaviors are increasing: findings from two sequential community surveys in South Australia", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hay et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hay et al. 2008). Similarly in the United Kingdom, there was 3 fold increase in the early 1990s for BN, particularly amongst females aged 10 to 39 years. The same study found that since 1996 the incidence has been declining, likely in part because of decreased symptom recognition and changes in service use ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Currin et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Currin et al. 2005). Contrary to other studies, evidence from a cohort of American college aged males and females from 1982, 1992, and 2002, concluded that the prevalence of BN decreased over time, from 4.2%, to 1.3% to 1.7% in females, and 1.1%, 0.4%, and 0% in males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S0033291705006148", "ISBN" : "0033291705", "ISSN" : "0033-2917", "PMID" : "16202192", "abstract" : "Background. Recent epidemiological data suggest a decline in bulimia nervosa (BN) incidence in primary care. We sought to examine BN point prevalence from 1982 to 2002 in a college population.Method. In 1982, 1992, and 2002, 800 women and 400 men were randomly sampled from a university for a study of health and eating patterns. Participation rates were 72% in women and 63% in men, resulting in n=2491 participants.Results. BN point prevalence decreased significantly in women over the period of observation. Eating Disorder Inventory Bulimia scores decreased across cohorts, and these decreases remained significant when male and female and Caucasian and non-Caucasian students were analyzed separately.Conclusion. These data support a decline in BN rates that cannot be attributed to changes in service utilization. Changing socio-cultural factors may explain a true decrease in BN incidence and prevalence.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heatherton", "given" : "Todd F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorer", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Joiner", "given" : "Thomas E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zalta", "given" : "Alyson K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Medicine", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "119-127", "title" : "Point prevalence of bulimia nervosa in 1982, 1992, and 2002", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel et al. 2006). Possible explanations of the discrepant findings are the altering of diagnostic criteria, shifting attitudes about mental health disorders, the inherent challenge in identifying patients who often try to keep their disease hidden, and various methodologies used ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel and Klump 2003). Sampling poses a specific issue as some studies recruited from very specific populations such as university students or public school students decreasing the generalizability of the findings. Small sample sizes of less than 500 people are also common. An example of the possibility that revised diagnostic criteria may lead to changes in the frequency of diagnosis of a disease is the dramatic increase in the incidence of BN from pre 1980 to post 1980. The true incidence may have increased or the increase may be attributed to the publication of the DSM-III where BN was first recognized as its own diagnostic category ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek and van Hoeken 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek and van Hoeken 2003). While the results should be interpreted with caution, the evidence seems to indicate that in Western societies, all three types of eating disorders, AN, BN, and BED may be becoming more common. Ethnicity and Culture: Understanding the roles of ethnicity and culture in eating disorder development is challenging. The concepts of ethnicity and culture are often inappropriately interchanged and are intrinsically connected making it next to impossible to study the effect of ethnicity or culture without confounding. Studying eating disorders in a global context adds additional challenges because environmental factors like the availability of doctors may be unrelated to culture but greatly impact the diagnosis and measurement of the disease. Several studies of eating have been conducted in multiple ethnicities from the same country in an attempt to understand ethnic and cultural effects on the development of eating disorders. Though it is tempting to assume that all people living in the same country have a shared culture and that the differences found between ethnicities would related to their genetics, this is an appropriate conclusion. Within a country there are innumerable subcultures, many of which are highly associated with ethnicity. Therefore, the results of the studies included in this review are unable to conclude if ethnicity is influencing the development of eating disorders because of underlying genetic differences or because people from different ethnic backgrounds are part of different subcultures. Anorexia Nervosa - Eating disorders are often cited as a Western disease however there is evidence that AN is found worldwide. In non-Western countries the prevalence of AN is estimated to be between 0.002% to 0.9%, significantly lower than the estimated prevalence of 0.3 to 3% for females and 0.24% for males in Western countries ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.maturitas.2013.04.014", "ISSN" : "1873-4111", "PMID" : "23706279", "abstract" : "Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.", "author" : [ { "dropping-particle" : "", "family" : "Meczekalski", "given" : "Blazej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Podfigurna-Stopa", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulski", "given" : "Krzysztof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "7" ] ] }, "page" : "215-220", "publisher" : "Elsevier Ireland Ltd", "title" : "Long-term consequences of anorexia nervosa", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-4", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/eat.parative", "author" : [ { "dropping-particle" : "", "family" : "Marques", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chih-nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chosak", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belo Diniz", "given" : "Juliana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "412-420", "title" : "Comparative prevalence, correlates of impairment, and service utilization for eating disorders across U.S. ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.appet.2013.01.005", "ISSN" : "1095-8304", "PMID" : "23348361", "abstract" : "During the last 25 years, the careful examination of the eating behavior of individuals with eating disorders has provided critical insights into the nature of these disorders. Crucially, studies investigating components of different eating behaviors have documented that Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED) are characterized by objective disturbances in eating patterns that are significantly different than behaviors exhibited by individuals who do not have these eating disorders. The detailed description of the disturbances in eating behavior has helped to identify diagnostic criteria associated with each disorder, and has led to important hypotheses about the underlying pathophysiology. These advances in understanding have provided, and continue to provide, a foundation for translational research and for the development of novel treatment interventions. This review is based on a presentation given by B. Timothy Walsh, M.D. at the 40th anniversary symposium of the Columbia University Appetite talks outlining the evolution of the discovery of the characteristic eating disturbances seen with each disorder.", "author" : [ { "dropping-particle" : "", "family" : "Heaner", "given" : "Martica K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Appetite", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "185-188", "publisher" : "Elsevier Ltd", "title" : "A history of the identification of the characteristics eating disturbances of bulimia nervosa, binge eating disorders and anorexia nervosa", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-7", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013). A meta-analysis of all reports including grey literature of AN in non-Western nations, taking country, diagnostic criteria, prevalence of cases, presence of weight concern in patients, and level of Western influence into consideration found that there are reported cases of AN worldwide, even in people who are unlikely to have experienced any Western influence. The most significant difference between the cases of AN in Western countries versus non-Western countries is the presence of weight concerns as a motivating factor for food refusal. If weight concerns are removed as a diagnostic criteria for AN, the prevalence of AN is very similar in Western and non-Western countries ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1351-0126", "PMID" : "11896858", "abstract" : "Anorexia nervosa is currently considered a disorder confined to Western culture. Its recent identification in non-Western societies and different subcultures within the Western world has provoked a theory that Western cultural ideals of slimness and beauty have infiltrated these societies. The biomedical definition of anorexia nervosa emphasizes fat-phobia in the presentation of anorexia nervosa. However, evidence exists that suggests anorexia nevosa can exist without the Western fear of fatness and that this culturally biased view of anorexia nervosa may obscure health care professionals' understanding of a patient's own cultural reasons for self-starvation, and even hinder their recovery.", "author" : [ { "dropping-particle" : "", "family" : "Simpson", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric and Mental Health Nursing", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2002", "2" ] ] }, "page" : "65-71", "title" : "Anorexia nervosa and culture", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Simpson 2002; Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Simpson 2002; Keel and Klump 2003). Though ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Keel and Klump (2003)", "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Keel and Klump (2003) concluded that AN occurs in all ethnicities and in all cultures, a study in Curacao, a Caribbean island, found an overall incidence of 1.82 cases of AN per 100 000 persons per year without a single case in Black females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "Van", "family" : "Harten", "given" : "Peter N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hermans", "given" : "Karin M E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katzman", "given" : "Melanie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matroos", "given" : "Glenn E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Susser", "given" : "Ezra S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "748-752", "title" : "The Incidence of Anorexia Nervosa on Cura\u00e7ao", "type" : "article-journal", "volume" : "162" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Harten et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Harten et al. 2005) despite Curacao being under a strong Western influence at the time of the study. Similarly, in the United States, a study including 2046 females from the NHLBI (The National Heart, Lung, and Blood Institute) Growth and Health Survey found that of the 1061 black females participating in the study, not one was diagnosed with AN, despite 1.5% of the white females participating having the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-953X", "PMID" : "12832249", "abstract" : "OBJECTIVE: Epidemiological studies of eating disorders in the United States have focused on white women and girls, and the prevalence of eating disorders in ethnic minority groups is unknown. This study examined the prevalence of anorexia nervosa, bulimia nervosa, and binge eating disorder in a geographically and economically diverse community sample of young white and black women who previously participated in the 10-year National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study. METHOD: All NHLBI Growth and Health Study participants were recruited for this study. A two-stage case finding method was used, consisting of a telephone screening (sensitivity=0.90, specificity=0.98) and an in-person confirmatory diagnostic interview. RESULTS: A total of 86.0% of the original NHLBI Growth and Health Study cohort participated, including 985 white women (mean age=21.3) and 1,061 black women (mean age=21.5). Fifteen white (1.5%) and no black women met lifetime criteria for anorexia nervosa; more white women (N=23, 2.3%) than black women (N=4, 0.4%) met criteria for bulimia nervosa; binge eating disorder also was more common among white women (N=27, 2.7%) than black women (N=15, 1.4%). Few women (white: N=16, 28.1%; black: N=1, 5.3%) ever had received treatment for an eating disorder. CONCLUSIONS: Results suggest that eating disorders, especially anorexia nervosa and bulimia nervosa, are more common among white women than among black women. The low treatment rates in both groups suggest that health professionals need to be more alert to the possibility of eating disorders in women.", "author" : [ { "dropping-particle" : "", "family" : "Striegel-Moore", "given" : "Ruth H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohm", "given" : "Faith a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraemer", "given" : "Helena C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "C Barr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Patricia B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiber", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "page" : "1326-1331", "title" : "Eating disorders in white and black women", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Striegel-Moore et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Striegel-Moore et al. 2003). Another study conducted in the United States investigating 5191 adults and 1170 adolescents who are African American and Caribbean Black found that the lifetime prevalence of AN in the adult population was 0.15% for African Americans and 0% for Caribbean Blacks ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1353/hpu.2013.0027.Classification", "author" : [ { "dropping-particle" : "", "family" : "Taylor", "given" : "J Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caldwell", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baser", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matuski", "given" : "Niki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faison", "given" : "Nakesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Health Care Poor Underserved", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "289-310", "title" : "Classification and correlates of eating disorders among blacks: Findings from the National Survey of American Life", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Taylor et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Taylor et al. 2013), significantly lower than the estimated prevalence of 0.3 to 3% for females and 0.24% for males in Western countries. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.maturitas.2013.04.014", "ISSN" : "1873-4111", "PMID" : "23706279", "abstract" : "Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.", "author" : [ { "dropping-particle" : "", "family" : "Meczekalski", "given" : "Blazej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Podfigurna-Stopa", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulski", "given" : "Krzysztof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "7" ] ] }, "page" : "215-220", "publisher" : "Elsevier Ireland Ltd", "title" : "Long-term consequences of anorexia nervosa", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-4", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/eat.parative", "author" : [ { "dropping-particle" : "", "family" : "Marques", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chih-nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chosak", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belo Diniz", "given" : "Juliana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "412-420", "title" : "Comparative prevalence, correlates of impairment, and service utilization for eating disorders across U.S. ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.appet.2013.01.005", "ISSN" : "1095-8304", "PMID" : "23348361", "abstract" : "During the last 25 years, the careful examination of the eating behavior of individuals with eating disorders has provided critical insights into the nature of these disorders. Crucially, studies investigating components of different eating behaviors have documented that Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED) are characterized by objective disturbances in eating patterns that are significantly different than behaviors exhibited by individuals who do not have these eating disorders. The detailed description of the disturbances in eating behavior has helped to identify diagnostic criteria associated with each disorder, and has led to important hypotheses about the underlying pathophysiology. These advances in understanding have provided, and continue to provide, a foundation for translational research and for the development of novel treatment interventions. This review is based on a presentation given by B. Timothy Walsh, M.D. at the 40th anniversary symposium of the Columbia University Appetite talks outlining the evolution of the discovery of the characteristic eating disturbances seen with each disorder.", "author" : [ { "dropping-particle" : "", "family" : "Heaner", "given" : "Martica K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Appetite", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "185-188", "publisher" : "Elsevier Ltd", "title" : "A history of the identification of the characteristics eating disturbances of bulimia nervosa, binge eating disorders and anorexia nervosa", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-7", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-8", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek and van Hoeken 2003; Currin et al. 2005; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek and van Hoeken 2003; Currin et al. 2005; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013). The study by Taylor et al. (2003) partially supports ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Keel and Klump's (2003)", "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Keel and Klump's (2003) theory that preoccupation with weight is a culturally driven attribute. When preoccupation with weight was removed as a diagnostic criteria, there was an increase in prevalence of AN of 0.21% in the African American population though there was no increase in the Caribbean Black population. This result highlights the confusion regarding the role of culture and the role in genetics in ethnicity. The increase in prevalence of AN in African Americans but not Caribbean Blacks could be because of underlying genetic differences that alter the predisposition to the disease, or it could be reflective of African Americans and Caribbean Blacks being part of different subcultures that could alter the risk of AN. One study interested in determining the genetic versus cultural impact of ethnicity investigated the degree of acculturation of Asian-Americans and found that the prevalence of AN was lower than in the White American population independent of acculturation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Nicdao", "given" : "Ethel G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Seunghye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "S22-S26", "title" : "Prevalence and correlates of eating disorders among Asian Americans: Results from the National Latino and Asian American Study", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Nicdao et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Nicdao et al. 2007). While the results indicate underlying genetic differences, the results still may be confounded as the degree of acculturation may not capture all relevant elements of culture. Bulimia Nervosa – BN is significantly less studied than AN, particularly in the international context limiting the conclusions that can be made about the role of ethnicity and Westernization in the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel and Klump 2003). Despite the limited studies available, it is generally accepted that the prevalence of BN is lower in non-Western countries compared to Western countries. A possible explanation is the unique environment necessary for BN which includes the ability to access large quantities of food as well as having weight concerns driving the need to purge ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel and Klump 2003). The meta-analysis by ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Keel and Klump (2003)", "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Keel and Klump (2003) which found that AN exists worldwide no matter the degree the Western influence found the opposite for BN. There were no studies in non-Western countries reporting the presence of BN in an individual without exposure to Western ideals. Extrapolating from the evidence for AN which found that as countries became more Westernized, there was a transmission of Western beauty ideals emphasizing thinness which coincided with increases in the prevalence of AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1351-0126", "PMID" : "11896858", "abstract" : "Anorexia nervosa is currently considered a disorder confined to Western culture. Its recent identification in non-Western societies and different subcultures within the Western world has provoked a theory that Western cultural ideals of slimness and beauty have infiltrated these societies. The biomedical definition of anorexia nervosa emphasizes fat-phobia in the presentation of anorexia nervosa. However, evidence exists that suggests anorexia nevosa can exist without the Western fear of fatness and that this culturally biased view of anorexia nervosa may obscure health care professionals' understanding of a patient's own cultural reasons for self-starvation, and even hinder their recovery.", "author" : [ { "dropping-particle" : "", "family" : "Simpson", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric and Mental Health Nursing", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2002", "2" ] ] }, "page" : "65-71", "title" : "Anorexia nervosa and culture", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Simpson 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Simpson 2002) it is possible that BN is not as prevalent in non-Westernized countries because people who do not idealize thinness would not fear gaining weight and therefore would not purge to compensate after binging episodes. The importance of Western influence in causing weight concerns motivating eating disorders is supported by a study conducted in the United States Latino population which found that recent immigrants had the lowest rates of BN while those who have resided in the United States for 70% or more of their lives had the highest rates ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woo", "given" : "Meghan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Zhun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torres", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Xiao-li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striegel-moore", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "S15-S21", "title" : "Prevalence and correlates of eating disorders in Latinos in the United States", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Alegria et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Alegria et al. 2007). Similarly to the research conducted for AN, the prevalence of BN has been looked at in multiple ethnicities from one country. A study including 2046 females from the NHLBI Growth and Health Survey in the United States found that 2.3% of white females, but only 0.4% of black females had a lifetime diagnosis of BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-953X", "PMID" : "12832249", "abstract" : "OBJECTIVE: Epidemiological studies of eating disorders in the United States have focused on white women and girls, and the prevalence of eating disorders in ethnic minority groups is unknown. This study examined the prevalence of anorexia nervosa, bulimia nervosa, and binge eating disorder in a geographically and economically diverse community sample of young white and black women who previously participated in the 10-year National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study. METHOD: All NHLBI Growth and Health Study participants were recruited for this study. A two-stage case finding method was used, consisting of a telephone screening (sensitivity=0.90, specificity=0.98) and an in-person confirmatory diagnostic interview. RESULTS: A total of 86.0% of the original NHLBI Growth and Health Study cohort participated, including 985 white women (mean age=21.3) and 1,061 black women (mean age=21.5). Fifteen white (1.5%) and no black women met lifetime criteria for anorexia nervosa; more white women (N=23, 2.3%) than black women (N=4, 0.4%) met criteria for bulimia nervosa; binge eating disorder also was more common among white women (N=27, 2.7%) than black women (N=15, 1.4%). Few women (white: N=16, 28.1%; black: N=1, 5.3%) ever had received treatment for an eating disorder. CONCLUSIONS: Results suggest that eating disorders, especially anorexia nervosa and bulimia nervosa, are more common among white women than among black women. The low treatment rates in both groups suggest that health professionals need to be more alert to the possibility of eating disorders in women.", "author" : [ { "dropping-particle" : "", "family" : "Striegel-Moore", "given" : "Ruth H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohm", "given" : "Faith a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraemer", "given" : "Helena C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "C Barr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Patricia B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiber", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "page" : "1326-1331", "title" : "Eating disorders in white and black women", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Striegel-Moore et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Striegel-Moore et al. 2003). In a study of African American and Black Caribbean adults living in the United States, the lifetime prevalence of BN was 1.40% for the African Americans and 1.98% for the Caribbean Blacks, lower than the estimated prevalence of 0.88 to 4.6% for all females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11920-012-0282-y", "ISSN" : "1535-1645", "PMID" : "22644309", "abstract" : "Eating disorders are relatively rare among the general population. This review discusses the literature on the incidence, prevalence and mortality rates of eating disorders. We searched online Medline/Pubmed, Embase and PsycINFO databases for articles published in English using several keyterms relating to eating disorders and epidemiology. Anorexia nervosa is relatively common among young women. While the overall incidence rate remained stable over the past decades, there has been an increase in the high risk-group of 15-19 year old girls. It is unclear whether this reflects earlier detection of anorexia nervosa cases or an earlier age at onset. The occurrence of bulimia nervosa might have decreased since the early nineties of the last century. All eating disorders have an elevated mortality risk; anorexia nervosa the most striking. Compared with the other eating disorders, binge eating disorder is more common among males and older individuals.", "author" : [ { "dropping-particle" : "", "family" : "Smink", "given" : "Fr\u00e9d\u00e9rique R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Psychiatry Reports", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "406-414", "title" : "Epidemiology of eating disorders: incidence, prevalence and mortality rates", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1017/S0033291708003942", "ISBN" : "0033291708003", "ISSN" : "0033-2917", "PMID" : "18775085", "abstract" : "BACKGROUND: Little is known about the epidemiology of bulimia nervosa outside clinical settings. We report the incidence, prevalence and outcomes of bulimia nervosa using for the first time a nationwide study design. METHOD: To assess the incidence and natural course and outcomes of DSM-IV bulimia nervosa among women from the general population, women (n=2881) from the 1975-79 birth cohorts of Finnish twins were screened for lifetime eating disorders using a two-stage procedure consisting of a questionnaire screen and the Structured Clinical Interview for DSM-IV (SCID). Clinical recovery was defined as 1-year abstinence from bingeing and purging combined with a body mass index (BMI) 19 kg/m2. RESULTS: The lifetime prevalence of DSM-IV bulimia nervosa was 2.3%; 76% of the women suffered from its purging subtype and 24% from the non-purging subtype. The incidence rate of bulimia nervosa was 300/100000 person-years at the peak age of incidence, 16-20 years, and 150/100000 at 10-24 years. The 5-year clinical recovery rate was 55.0%. Less than a third of the cases had been detected by health-care professionals; detection did not influence outcome. After clinical recovery from bulimia nervosa, the mean levels of residual psychological symptoms gradually decreased over time but many women continued to experience significantly more body image problems and psychosomatic symptoms than never-ill women. CONCLUSIONS: Few women with bulimia nervosa are recognized in health-care settings. Symptoms of bulimia are relatively long-standing, and recovery is gradual. Many clinically recovered women experience residual psychological symptoms after attaining abstinence from bingeing and purging.", "author" : [ { "dropping-particle" : "", "family" : "Keski-Rahkonen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linna", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raevuori", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sihvola", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Medicine", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5" ] ] }, "page" : "823-831", "title" : "Incidence and outcomes of bulimia nervosa: a nationwide population-based study", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-6", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-7", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-8", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Favaro et al. 2003; Hoek and van Hoeken 2003; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Keski-Rahkonen et al. 2009; Preti et al. 2009; Smink et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Favaro et al. 2003; Hoek and van Hoeken 2003; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Keski-Rahkonen et al. 2009; Preti et al. 2009; Smink et al. 2012) and 0.10 to 1.5% for males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11920-012-0282-y", "ISSN" : "1535-1645", "PMID" : "22644309", "abstract" : "Eating disorders are relatively rare among the general population. This review discusses the literature on the incidence, prevalence and mortality rates of eating disorders. We searched online Medline/Pubmed, Embase and PsycINFO databases for articles published in English using several keyterms relating to eating disorders and epidemiology. Anorexia nervosa is relatively common among young women. While the overall incidence rate remained stable over the past decades, there has been an increase in the high risk-group of 15-19 year old girls. It is unclear whether this reflects earlier detection of anorexia nervosa cases or an earlier age at onset. The occurrence of bulimia nervosa might have decreased since the early nineties of the last century. All eating disorders have an elevated mortality risk; anorexia nervosa the most striking. Compared with the other eating disorders, binge eating disorder is more common among males and older individuals.", "author" : [ { "dropping-particle" : "", "family" : "Smink", "given" : "Fr\u00e9d\u00e9rique R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Psychiatry Reports", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "406-414", "title" : "Epidemiology of eating disorders: incidence, prevalence and mortality rates", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-3", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hudson et al. 2008; Preti et al. 2009; Smink et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hudson et al. 2008; Preti et al. 2009; Smink et al. 2012) in Western countries. Removing preoccupation with body weight resulted in a modest increase in the prevalence of BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1353/hpu.2013.0027.Classification", "author" : [ { "dropping-particle" : "", "family" : "Taylor", "given" : "J Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caldwell", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baser", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matuski", "given" : "Niki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faison", "given" : "Nakesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Health Care Poor Underserved", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "289-310", "title" : "Classification and correlates of eating disorders among blacks: Findings from the National Survey of American Life", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Taylor et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Taylor et al. 2013). These ethnic differences may reflect the consequences of subcultures, specifically what type of body shape is considered ideal, or the potential for underlying genetic differences predisposing individuals to BN. Binge Eating Disorder - BED is distinct from AN and BN because it does not include weight preoccupation as a diagnostic criteria ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "American Psychiatric Association", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "American Psychiatric Association", "publisher-place" : "Arlington, Virginia", "title" : "Diagnostic and statistical manual of mental disorders", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "(American Psychiatric Association, 2013)", "previouslyFormattedCitation" : "(American Psychiatric Association 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(American Psychiatric Association, 2013). Weight preoccupation is predominantly a Western concern ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1351-0126", "PMID" : "11896858", "abstract" : "Anorexia nervosa is currently considered a disorder confined to Western culture. Its recent identification in non-Western societies and different subcultures within the Western world has provoked a theory that Western cultural ideals of slimness and beauty have infiltrated these societies. The biomedical definition of anorexia nervosa emphasizes fat-phobia in the presentation of anorexia nervosa. However, evidence exists that suggests anorexia nevosa can exist without the Western fear of fatness and that this culturally biased view of anorexia nervosa may obscure health care professionals' understanding of a patient's own cultural reasons for self-starvation, and even hinder their recovery.", "author" : [ { "dropping-particle" : "", "family" : "Simpson", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric and Mental Health Nursing", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2002", "2" ] ] }, "page" : "65-71", "title" : "Anorexia nervosa and culture", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Simpson 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Simpson 2002) and perhaps also ethnicity specific as evidenced by White American females experiencing a larger discrepancy between their current weight and ideal weight and being more concerned about dieting, regardless of current BMI compared to their African American counterparts ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1471-0153", "PMID" : "15001011", "abstract" : "There is a growing literature on the relationship between race/ethnicity and body image and eating disorders, but the conclusions are still unclear. We therefore examined racial/ethnic influences on body image and eating behaviors in 108 Caucasian, 46 African American, and 40 Asian female undergraduates. Participants completed the Figure Rating Scale (FRS) and the Eating Habits Questionnaire (EHQ) to assess body image and eating pathology. Caucasians had greater body discrepancy (difference between current and ideal) than Asians (P=.05) and higher EHQ scores (P<.0001) than both Asians and African Americans. African Americans chose a larger ideal body size than the other groups (P=.005). However, Asian women had a significantly lower body mass index (BMI) than both groups (P<.0001). After controlling for BMI, ideal body size differences were minimized (P=.08). Also, now, both Caucasians and Asians had greater body discrepancy (P<.0001) and EHQ scores (P<.0001) than African Americans. Our findings help reconcile inconsistencies in the literature by demonstrating the impact of controlling for BMI when comparing body image and eating behaviors in individuals from different racial/ethnic backgrounds.", "author" : [ { "dropping-particle" : "", "family" : "Gluck", "given" : "Marci E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geliebter", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eating Behaviors", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "1" ] ] }, "page" : "143-151", "title" : "Racial/ethnic differences in body image and eating behaviors", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gluck and Geliebter 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gluck and Geliebter 2002). Unlike AN and BN where generally there is a higher prevalence in populations of European heritage, most studies have found that the prevalence of BED is as high as or higher in Black Africans compared to Whites. Very limited data is available regarding other ethnicities. The lifetime prevalence of BED is estimated to be between 2.5 to 3.5% for females and 1.5 to 2.0% for males in Western countries ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Spitzer", "given" : "R.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devlin", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "Timothy B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasin", "given" : "Deborah S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stunkard", "given" : "A.J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wadden", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Susan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Agras", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nonas", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "191-204", "title" : "Binge eating disorder: A multisite field trial of the diagnostic criteria", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Spitzer", "given" : "R.L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Susan Z", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wadden", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "M D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stunkard", "given" : "A.J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devlin", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mitchell", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hasin", "given" : "Deborah S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horne", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "1993" ] ] }, "page" : "137-154", "title" : "Binge eating disorder: Its further validation in a multi-site study.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0276-3478", "PMID" : "10191993", "abstract" : "OBJECTIVE: The authors investigated the prevalence of binge eating behavior in a general female Austrian population. METHOD: A random sample of 1,000 women (age range 15a to 85a) was interviewed by dieticians over the phone. Some screening instruments were used to detect binge eating behavior. RESULTS: Of the entire sample, 122 met the diagnostic criteria for binge eating, 84 for binge eating syndrome, and 33 for binge eating disorder (BED). The point prevalence of bulimia nervosa was 1.5%. Women with binge eating episodes carried out more frequently one or more diets within the previous year, and more frequently exhibited a restrained eating behavior than did women without binge eating behavior. Underweight women more often met the diagnostic criteria for bulimia nervosa nonpurging type than did normal weight, overweight, and obese women, while overweight and obese women more frequently met the diagnostic criteria for BED. DISCUSSION: Our findings indicate that binge eating appears to be a fairly common behavior in women. Dieting, chronic restrained eating, and excessive exercise may be important triggers for BED and bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Kinzl", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Traweger", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trefalt", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangweth", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biebl", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "4" ] ] }, "page" : "287-292", "title" : "Binge eating disorder in females: a population-based investigation", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0001-690X", "PMID" : "11473506", "abstract" : "OBJECTIVE: To examine the prevalence, incidence and prospective risk factors for eating disorders (ED) among young adult females. METHOD: Using a prospective design, a randomly selected sample of 1157 females (18-30 years) from the general population was examined with questionnaires for establishing ED diagnoses, self-esteem, body concern, coping and perceived social support. RESULTS: The prevalence of ED was 3.2% and the 2-year first-time incidence was 0.0105 (n=8). Subjects in the extended incidence group (n=34) reported significantly lower self-esteem and perceived social support, and higher body concern and relative use of escape-avoidance coping, at the onset of the study in 1997, compared to controls (n=643). Furthermore, they reported a significant increase in body concern and relative use of escape-avoidance coping, and a significant decrease in self-esteem compared to controls from 1997 to 1999. CONCLUSION: These factors may be considered as risk factors for later development of ED among young adult women.", "author" : [ { "dropping-particle" : "", "family" : "Ghaderi", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Acta Psychiatrica Scandinavica", "id" : "ITEM-5", "issue" : "2", "issued" : { "date-parts" : [ [ "2001", "8" ] ] }, "page" : "122-130", "title" : "Prevalence, incidence and prospective risk factors for eating disorders", "type" : "article-journal", "volume" : "104" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Spitzer et al. 1992, 1993; Kinzl et al. 1999; Ghaderi and Scott 2001; Hudson et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Spitzer et al. 1992, 1993; Kinzl et al. 1999; Ghaderi and Scott 2001; Hudson et al. 2008). A study conducted in African Americans and Caribbean Blacks in the United States partaking in the National Survey of American Life (NSAL) found that the lifetime prevalence of BED in African American adults is 5.02%, and 5.78% for Caribbean Black adults ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1353/hpu.2013.0027.Classification", "author" : [ { "dropping-particle" : "", "family" : "Taylor", "given" : "J Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caldwell", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baser", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matuski", "given" : "Niki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faison", "given" : "Nakesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Health Care Poor Underserved", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "289-310", "title" : "Classification and correlates of eating disorders among blacks: Findings from the National Survey of American Life", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Taylor et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Taylor et al. 2013). While this study had an exceptionally high prevalence of BED, a study including the pooled data from the NIMH (National Institute of Mental Health) Collaborative Psychiatric Epidemiological Studies in the United States found the lifetime prevalence of BED to be 1.91% in non-Latino Whites, 2.71% in Latinos, 1.66% in Asians, and 2.22% in African Americans females and 0.75%, 1.67%, 0.95%, and 0.97% respectively in males. The only statistically significant differences between groups existed for non-Latino White males versus Latino males, and non-Latino White versus African American males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.parative", "author" : [ { "dropping-particle" : "", "family" : "Marques", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chih-nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chosak", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belo Diniz", "given" : "Juliana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "412-420", "title" : "Comparative prevalence, correlates of impairment, and service utilization for eating disorders across U.S. ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Marques et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Marques et al. 2011). Similar lifetime prevalence estimated were found in another study in the United States focusing on the Latino population, 1.55% for males, and 2.31% for females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woo", "given" : "Meghan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Zhun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torres", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Xiao-li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striegel-moore", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "S15-S21", "title" : "Prevalence and correlates of eating disorders in Latinos in the United States", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Alegria et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Alegria et al. 2007). A study involving a biracial population-based cohort of males and females participating in a longitudinal study of cardiovascular risk factor development had similar results indicating the prevalence of BED is approximately the same in White and Black populations. The Revised Questionnaire on Eating and Weight patterns was used to establish BED status among the 3948 (55% females, 48% Black) participants, who were 28 to 49 years of age. Prevalence of BED was 1.5% overall, with similar rates among Black females (2.2%), White females (2.0%), and White males (1.2%), while Black males had a significant lower prevalence (0.4%). ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0883-6612", "PMID" : "9989331", "abstract" : "This article examined the prevalence of binge eating disorder (BED), obesity, and depressive symptomatology in a biracial, population-based cohort of men and women participating in a longitudinal study of cardiovascular risk factor development. The Revised Questionnaire on Eating and Weight Patterns was used to establish BED status among the 3,948 (55% women, 48% Black) participants (age 28-40 years). Body mass index (BMI: kg/m2) was used to define overweight (BMI > or = 27.3 in women and > or = 27.8 in men). Depressive symptomatology was assessed with the Center for Epidemiologic Study Depression Scale. Prevalence of BED was 1.5% in the cohort overall, with similar rates among Black women, White women, and White men. Black men had substantially lower BED rates. Depressive symptomatology was markedly higher among individuals with BED. Among overweight participants, BED prevalence (2.9%) was almost double that of the overall cohort. There were no differences in BED rates between over-weight Black and White women. Thus, BED was common in the general population, with comparable rates among Black women, White women, and White men, but low rates among Black men. Obesity was associated with substantially higher prevalence of BED. Treatment studies that target obese men and minority women with BED are indicated.", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "M D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "C E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fitzgibbon", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiner", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Behavioral Medicine", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1998", "1" ] ] }, "page" : "227-232", "title" : "Prevalence of binge eating disorder, obesity, and depression in a biracial cohort of young adults", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Smith et al. 1998)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Smith et al. 1998). While less studied, it appears that the lifetime prevalence of BED in Asian Americans is within the general range of the White population with 2.67% of females and 1.36% of males being affected by the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Nicdao", "given" : "Ethel G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Seunghye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "S22-S26", "title" : "Prevalence and correlates of eating disorders among Asian Americans: Results from the National Latino and Asian American Study", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Nicdao et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Nicdao et al. 2007)The higher prevalence of BED in Blacks compared to Whites may be explained by this lack of weight preoccupation. BN, which involves the same binge eating behaviour seen in BED, but also includes a purging element motivated by the fear of gaining is more prevalent in White females compared to Black females. Even within the BED population, White females are significantly more concerned about eating, dietary restraint, shape concern, and weight concern compared to Black females, despite on average being less overweight ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-953X", "PMID" : "11532731", "abstract" : "OBJECTIVE: Binge eating disorder was introduced in DSM-IV as a psychiatric disorder needing further study. This community-based study describes the relationship between race and clinical functioning in black and white women with and without binge eating disorder. METHOD: A group of 150 women with binge eating disorder (52 black, 98 white) and a race-matched group of 150 healthy comparison subjects were recruited from the community. Eating and psychiatric symptoms were assessed through interviews and self-report. RESULTS: Black and white women with binge eating disorder differed significantly on numerous eating disorder features, including binge frequency, restraint, history of other eating disorders, treatment-seeking behavior, and concerns with eating, weight, and shape. Black and white healthy comparison subjects differed significantly in obesity rates. CONCLUSIONS: For both black and white women, binge eating disorder was associated with significant impairment in clinical functioning. Yet, racial differences in clinical presentation underscore the importance of considering race in psychopathology research.", "author" : [ { "dropping-particle" : "", "family" : "Pike", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohm", "given" : "F a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striegel-Moore", "given" : "R H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilfley", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2001", "9" ] ] }, "page" : "1455-1460", "title" : "A comparison of black and white women with binge eating disorder", "type" : "article-journal", "volume" : "158" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Pike et al. 2001)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Pike et al. 2001). Because a smaller proportion of African Americans have weight concerns, there is the potential that the population is less likely on average to engage in purging behaviour compared to their White American counterparts. Therefore they receive a diagnosis of BED rather than BN. This is supported by studies such as ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1353/hpu.2013.0027.Classification", "author" : [ { "dropping-particle" : "", "family" : "Taylor", "given" : "J Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caldwell", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baser", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matuski", "given" : "Niki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faison", "given" : "Nakesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Health Care Poor Underserved", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "289-310", "title" : "Classification and correlates of eating disorders among blacks: Findings from the National Survey of American Life", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Taylor et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Taylor et al. 2013) which found that when weight preoccupation was removed as a criteria, the prevalence of BN in African Americans and Caribbean Blacks increases. Summary of the role of ethnicity and culture in the development of eating disorders – It is generally accepted that the lifetime prevalence of AN according to the current diagnostic criteria is higher in the White population compared to other ethnicities. However, the degree of Westernization may play an important role, especially in the development of AN and BN which both require an individual to have preoccupations with their weight to receive a diagnosis. The idealization of a slim body type and weight preoccupation is a Western phenomenon and there is evidence that the more a person is influenced by Western culture, the more likely it is for them to develop either AN or BN. However, studies have also shown that regardless of acculturation to Western ideals, there are still some significant differences between the prevalence of eating disorders in people of different ethnic backgrounds who have been raised in the same country. These differences may be reflective of subcultures existing within countries that may be strongly associated with ethnicity or that the genetic differences between ethnicities may alter the baseline risking of an individual for developing an eating disorder and that exposure to Western ideals, particularly that a low weight makes one attractive, may modulate the risk. 2.6 Heritability of eating disordersThere is very strong evidence that eating disorders are moderately to highly heritable. In a 2005 review of family studies investigating the heritability of AN and BN, all but one study reported increased risk of eating disorders in those with family members displaying eating disorders ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1375/183242705774310114", "ISSN" : "1832-4274", "PMID" : "16212836", "abstract" : "Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "467-482", "title" : "Eating disorders: from twin studies to candidate genes and beyond", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Slof-Op \u2019t Landt et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Slof-Op ’t Landt et al. 2005). It is estimated that the lifetime risk of AN and BN among female relatives of a person with an eating disorder is 7 to 20 times higher than that of the general population ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-953X", "PMID" : "10698815", "abstract" : "OBJECTIVE: Lifetime rates of full and partial anorexia nervosa and bulimia nervosa were determined in first-degree relatives of diagnostically pure proband groups and relatives of matched, never-ill comparison subjects. METHOD: Rates of each eating disorder were obtained for 1,831 relatives of 504 probands on the basis of personal structured clinical interviews and family history. Best-estimate diagnoses based on all available information were rendered without knowledge of proband status and pedigree identity. Only definite and probable diagnoses were considered. RESULTS: Whereas anorexia nervosa was rare in families of the comparison subjects, full and partial syndromes of anorexia nervosa aggregated in female relatives of both anorexic and bulimic probands. For the full syndrome of anorexia nervosa, the relative risks were 11.3 and 12.3 in female relatives of anorexic and bulimic probands, respectively. Bulimia nervosa was more common than anorexia nervosa in female relatives of comparison subjects, but it, too, aggregated in the families of ill probands; the corresponding relative risks for bulimia nervosa were 4.2 and 4.4 for female relatives of anorexic and bulimic probands, respectively. When partial syndromes of anorexia nervosa and bulimia nervosa were considered, relative risks fell by one-half in each group of ill probands. CONCLUSIONS: Both anorexia nervosa and bulimia nervosa are familial. Their cross-transmission in families suggests a common, or shared, familial diathesis. The additional observation that familial aggregation and cross-transmission extend to milder phenotypes suggests the validity of their inclusion in a continuum of familial liability.", "author" : [ { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freeman", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lampert", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diamond", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2000", "3" ] ] }, "page" : "393-401", "title" : "Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes", "type" : "article-journal", "volume" : "157" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0193-953X", "PMID" : "11416922", "abstract" : "Data described earlier are clear in establishing a role for genes in the development of eating abnormalities. Estimates from the most rigorous studies suggest that more than 50% of the variance in eating disorders and disordered eating behaviors can be accounted for by genetic effects. These high estimates indicate a need for studies identifying the specific genes contributing to this large proportion of variance. Twin and family studies suggest that several heritable characteristics that are commonly comorbid with AN and BN may share genetic transmission with these disorders, including anxiety disorders or traits, body weight, and possibly major depression. Moreover, some developmental research suggests that the genes involved in ovarian hormones or the genes that these steroids affect also may be genetically linked to eating abnormalities. Molecular genetic research of these disorders is in its infant stages. However, promising areas for future research have already been identified (e.g., 5-HT2A receptor gene, UCP-2/UCP-3 gene, and estrogen receptor beta gene), and several large-scale linkage and association studies are underway. These studies likely will provide invaluable information regarding the appropriate phenotypes to be included in genetic studies and the genes with the most influence on the development of these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Klump", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatric Clinics of North America", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2001", "6" ] ] }, "page" : "215-225", "title" : "The evolving genetic foundations of eating disorders", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Strober et al. 2000; Klump et al. 2001)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Strober et al. 2000; Klump et al. 2001). Estimates of the heritability of eating disorders range from 0.28 to 0.76 for twin studies of AN and 0.30 to 0.83 for twin studies of BN. In many of these studies, broad definitions for disease diagnosis were used to increase statistical power because of the low prevalence of the diseases ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1375/183242705774310114", "ISSN" : "1832-4274", "PMID" : "16212836", "abstract" : "Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "467-482", "title" : "Eating disorders: from twin studies to candidate genes and beyond", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Slof-Op \u2019t Landt et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Slof-Op ’t Landt et al. 2005). Interestingly, a large portion of the remaining variance for the risk of developing either AN or BN is accounted for by non-shared environmental factors, estimated to be between 0.17 to 0.50 compared to the relatively low estimates of the effect of shared environmental factors ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0276-3478", "PMID" : "11920974", "abstract" : "OBJECTIVE: Nonshared environmental influences are experiences that are unique to siblings reared in the same family. We review studies highlighting the importance of nonshared factors for the development of eating disorders and suggest areas for future research. METHODS: Findings from behavioral genetic studies of eating disorders as well as methodological issues are reviewed. RESULTS: Twin studies suggest that approximately 17%-46% of the variance in both anorexia nervosa (AN) and bulimia nervosa (BN) can be accounted for by nonshared environmental factors. Studies directly examining these influences are scarce, although initial data indicate that differential paternal relationships, body weight teasing, peer group experiences, and life events may account for the development of eating pathology in one sibling versus another. DISCUSSION: Additional research is needed to identify specific nonshared environmental influences on eating disorders such as differential parental and sibling treatment, disparate peer group characteristics, and differential experience of life events such as physical and sexual abuse.", "author" : [ { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wonderlich", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehoux", "given" : "Pascale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lilenfeld", "given" : "Lisa R R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "3" ] ] }, "page" : "118-135", "title" : "Does environment matter? A review of nonshared environment and eating disorders", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1375/183242705774310114", "ISSN" : "1832-4274", "PMID" : "16212836", "abstract" : "Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "467-482", "title" : "Eating disorders: from twin studies to candidate genes and beyond", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Klump et al. 2002; Slof-Op \u2019t Landt et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Klump et al. 2002; Slof-Op ’t Landt et al. 2005). The lifetime risk of having BED is estimated to be between 1.9 and 2.2 times higher for those with a relative with the disease and twin studies have estimated the heritability is between 0.41 and 0.57 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/7854", "author" : [ { "dropping-particle" : "", "family" : "Thornton", "given" : "Laura M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mazzeo", "given" : "Suzanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Topics in Behavioral Neuroscience", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "141-156", "title" : "The heritability of eating disorders: Methods and current findings", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Thornton et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Thornton et al. 2011).2.7 Genetics of eating disorders A variety of different types of studies have been conducted to determine the genetic architecture of eating disorders including linkage studies, candidate gene approaches, and GWAS. Linkage studies use related individuals to identify regions of the genome containing genes that predispose individuals to a disease have provided limited ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Teare", "given" : "M Dawn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrett", "given" : "Jennifer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "1036-1044", "title" : "Genetic Epidemiology 2: Genetic linkage studies", "type" : "article-journal", "volume" : "366" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Teare and Barrett 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Teare and Barrett 2005). Candidate gene studies investigate genes that have been selected based on their physiological, biochemical, and functional aspects ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "8627872813", "ISSN" : "1449-2288", "PMID" : "17998950", "abstract" : "Although it has been widely applied in identification of genes responsible for biomedically, economically, or even evolutionarily important complex and quantitative traits, traditional candidate gene approach is largely limited by its reliance on the priori knowledge about the physiological, biochemical or functional aspects of possible candidates. Such limitation results in a fatal information bottleneck, which has apparently become an obstacle for further applications of traditional candidate gene approach on many occasions. While the identification of candidate genes involved in genetic traits of specific interest remains a challenge, significant progress in this subject has been achieved in the last few years. Several strategies have been developed, or being developed, to break the barrier of information bottleneck. Recently, being a new developing method of candidate gene approach, digital candidate gene approach (DigiCGA) has emerged and been primarily applied to identify potential candidate genes in some studies. This review summarizes the progress, application software, online tools, and challenges related to this approach.", "author" : [ { "dropping-particle" : "", "family" : "Zhu", "given" : "Mengjin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Shuhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Biological Sciences", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "1" ] ] }, "page" : "420-427", "title" : "Candidate gene identification approach: progress and challenges", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Zhu and Zhao 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Zhu and Zhao 2007). GWAS are studies attempt to identify common genetic variants that contribute to disease risk using markers from the entire genome ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pcbi.1002822", "ISSN" : "1553-7358", "PMID" : "23300413", "abstract" : "Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.", "author" : [ { "dropping-particle" : "", "family" : "Bush", "given" : "William S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moore", "given" : "Jason H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Computational Biology", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "e1002822", "title" : "Chapter 11: Genome-wide association studies.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bush and Moore 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bush and Moore 2012). Linkage studies have provided limited results in the context of eating disorders. In a collaboration of 5 studies, there were no AN-affected relative pairs with nonparametric linkage (NPL) scores above 1.80, however people with the restrictive subtype of AN had a linkage peak at 1p33-36 (NPL score = 3.03) and a peak at 4q12-14 (NPL score = 2.44). Investigating the traits of drive for thinness and obsessionality in the AN sample revealed three possible linkages on chromosome 1q31 (LOD (logarithm of odds) score = 3.46) for both traits, 2p11 (LOD score = 2.22) for obsessionality, and 13q13 (LOD score = 2.5) for drive for thinness. For BN, chromosome 10p13 (LOD = 2.92), and 10p14 (LOD score = 2.7) achieved significant linkage results, while 14q22-23 were almost significant (LOD score = 1.97). When regular vomiting in those with BN was used as a phenotype, the linkage on chromosome 10p13 was strengthened (LOD=3.39) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1375/183242705774310114", "ISSN" : "1832-4274", "PMID" : "16212836", "abstract" : "Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "467-482", "title" : "Eating disorders: from twin studies to candidate genes and beyond", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Slof-Op \u2019t Landt et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Slof-Op ’t Landt et al. 2005). Genome wide association studies (GWAS) are studies which identify common genetic variants that contribute to disease risk ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1371/journal.pcbi.1002822", "ISSN" : "1553-7358", "PMID" : "23300413", "abstract" : "Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.", "author" : [ { "dropping-particle" : "", "family" : "Bush", "given" : "William S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moore", "given" : "Jason H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "PLoS Computational Biology", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "e1002822", "title" : "Chapter 11: Genome-wide association studies.", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bush and Moore 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bush and Moore 2012) as well as candidate gene studies investigating genes selected based on physiological, biochemical, and functional aspects ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "8627872813", "ISSN" : "1449-2288", "PMID" : "17998950", "abstract" : "Although it has been widely applied in identification of genes responsible for biomedically, economically, or even evolutionarily important complex and quantitative traits, traditional candidate gene approach is largely limited by its reliance on the priori knowledge about the physiological, biochemical or functional aspects of possible candidates. Such limitation results in a fatal information bottleneck, which has apparently become an obstacle for further applications of traditional candidate gene approach on many occasions. While the identification of candidate genes involved in genetic traits of specific interest remains a challenge, significant progress in this subject has been achieved in the last few years. Several strategies have been developed, or being developed, to break the barrier of information bottleneck. Recently, being a new developing method of candidate gene approach, digital candidate gene approach (DigiCGA) has emerged and been primarily applied to identify potential candidate genes in some studies. This review summarizes the progress, application software, online tools, and challenges related to this approach.", "author" : [ { "dropping-particle" : "", "family" : "Zhu", "given" : "Mengjin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Shuhong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Biological Sciences", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "1" ] ] }, "page" : "420-427", "title" : "Candidate gene identification approach: progress and challenges", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Zhu and Zhao 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Zhu and Zhao 2007) have also been widely used. The results of these studies in relation to eating disorders can be categorized into three main biological pathways, the serotonin pathway, the catecholamine pathway, and the pathway involved with neuropeptide and feeding regulation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1375/183242705774310114", "ISSN" : "1832-4274", "PMID" : "16212836", "abstract" : "Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "467-482", "title" : "Eating disorders: from twin studies to candidate genes and beyond", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Slof-Op \u2019t Landt et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Slof-Op ’t Landt et al. 2005)2.7.1 SerotoninSerotonin (5-HT) is involved with normal brain function including mood state, hunger, sex, sleep, memory, emotion, anxiety, and endocrine function ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/FBP.0b013e328357440d", "ISSN" : "1473-5849", "PMID" : "22854305", "abstract" : "Patients with anorexia nervosa (AN) show extreme dieting weight loss, hyperactivity, depression/anxiety, self-control, and behavioral impulsivity. 5-Hydroxytryptamine (5-HT; serotonin) is involved in almost all the behavioral changes observed in AN patients. Both genetic and environmental factors contribute toward the pathogenesis of AN. It is a frequent disorder among adolescent girls and young women and starts as an attempt to lose weight to look beautiful and attractive. Failure to see the turning point when fasting becomes unreasonable leads to malnutrition and AN. Tryptophan, the precursor of serotonin and an essential amino acid, is only available in the diet. It is therefore likely that excessive diet restriction and malnutrition decrease brain serotonin stores because the precursor is less available to the rate-limiting enzyme of 5-HT biosynthesis, which normally exists unsaturated with its substrate. Evidence shows that diet restriction-induced exaggerated feedback control over 5-HT synthesis and the smaller availability of tryptophan decreases serotonin neurotransmission at postsynaptic sites, leading to hyperactivity, depression, and behavioral impulsivity. A compensatory upregulation of postsynaptic 5-HT-1A receptors and hypophagic serotonin receptors may be involved in anxiety and suppression of appetite. It is suggested that tryptophan supplementation may improve pharmacotherapy in AN.", "author" : [ { "dropping-particle" : "", "family" : "Haleem", "given" : "Darakhshan Jabeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Behavioural Pharmacology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "page" : "478-495", "title" : "Serotonin neurotransmission in anorexia nervosa", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Haleem 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Haleem 2012). Symptoms of AN such as depression ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.maturitas.2013.04.014", "ISSN" : "1873-4111", "PMID" : "23706279", "abstract" : "Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.", "author" : [ { "dropping-particle" : "", "family" : "Meczekalski", "given" : "Blazej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Podfigurna-Stopa", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulski", "given" : "Krzysztof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "7" ] ] }, "page" : "215-220", "publisher" : "Elsevier Ireland Ltd", "title" : "Long-term consequences of anorexia nervosa", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Meczekalski et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Meczekalski et al. 2013), refusal to consume food, binging behaviour ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "American Psychiatric Association", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "American Psychiatric Association", "publisher-place" : "Arlington, Virginia", "title" : "Diagnostic and statistical manual of mental disorders", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "(American Psychiatric Association, 2013)", "previouslyFormattedCitation" : "(American Psychiatric Association 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(American Psychiatric Association, 2013), and hyperactivity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.22272", "ISSN" : "1098-108X", "PMID" : "24687461", "abstract" : "OBJECTIVE: Hyperactivity and elevated physical activity are both considered symptom characteristics of anorexia nervosa (AN). It has been suggested that a drive for activity (DFA) may underlie these expressions, yet research into DFA in AN remains scant. This study investigated DFA levels in patients with AN and its relation to AN severity. Furthermore, as physical exercise may be a way to reduce negative affect, the influence of negative affect (anxiety) on the role of DFA in AN was tested. METHOD: Two hundred and forty female patients with AN completed measures for DFA, eating disorder (ED) pathology, anxiety, and clinical parameters. RESULTS: A strong relation between DFA levels and ED pathology was found, which remained significant even after controlling for negative affect (anxiety). DISCUSSION: After much theorizing about DFA in AN this study provides empirical evidence for DFA as a hallmark feature of AN, independent of anxiety levels. Future research should shed light on the relationships between DFA, actual physical activity, and the course of AN. \u00a9 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014).", "author" : [ { "dropping-particle" : "", "family" : "Sternheim", "given" : "Lot", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danner", "given" : "Unna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elburg", "given" : "Annemarie", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating iDsorders", "id" : "ITEM-1", "issue" : "00", "issued" : { "date-parts" : [ [ "2014", "3", "29" ] ] }, "page" : "1-4", "title" : "Drive for activity in patients with anorexia nervosa", "type" : "article-journal", "volume" : "0" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Sternheim et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Sternheim et al. 2014) are all linked to circulating serotonin levels ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/FBP.0b013e328357440d", "ISSN" : "1473-5849", "PMID" : "22854305", "abstract" : "Patients with anorexia nervosa (AN) show extreme dieting weight loss, hyperactivity, depression/anxiety, self-control, and behavioral impulsivity. 5-Hydroxytryptamine (5-HT; serotonin) is involved in almost all the behavioral changes observed in AN patients. Both genetic and environmental factors contribute toward the pathogenesis of AN. It is a frequent disorder among adolescent girls and young women and starts as an attempt to lose weight to look beautiful and attractive. Failure to see the turning point when fasting becomes unreasonable leads to malnutrition and AN. Tryptophan, the precursor of serotonin and an essential amino acid, is only available in the diet. It is therefore likely that excessive diet restriction and malnutrition decrease brain serotonin stores because the precursor is less available to the rate-limiting enzyme of 5-HT biosynthesis, which normally exists unsaturated with its substrate. Evidence shows that diet restriction-induced exaggerated feedback control over 5-HT synthesis and the smaller availability of tryptophan decreases serotonin neurotransmission at postsynaptic sites, leading to hyperactivity, depression, and behavioral impulsivity. A compensatory upregulation of postsynaptic 5-HT-1A receptors and hypophagic serotonin receptors may be involved in anxiety and suppression of appetite. It is suggested that tryptophan supplementation may improve pharmacotherapy in AN.", "author" : [ { "dropping-particle" : "", "family" : "Haleem", "given" : "Darakhshan Jabeen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Behavioural Pharmacology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "page" : "478-495", "title" : "Serotonin neurotransmission in anorexia nervosa", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Haleem 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Haleem 2012). Serotonin levels are determined using 5-hydroxyindoleacetic acid (5-HIAA), the primary metabolite of serotonin. 5-HIAA level are elevated in both those suffering from AN and BN as well as those recovered from the diseases indicating the possible role of hyperserotonergic function ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00787-009-0085-9", "ISSN" : "1435-165X", "PMID" : "20033240", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders characterized by disordered eating behavior where the patient's attitude towards weight and shape, as well as their perception of body shape, are disturbed. Formal genetic studies on twins and families suggested a substantial genetic influence for AN and BN. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Hardly any of the positive findings achieved in these studies were unequivocally confirmed or substantiated in meta-analyses. This might be due to too small sample sizes and thus low power and/or the genes underlying eating disorders have not yet been analyzed. However, some studies that also used subphenotypes (e.g., restricting type of AN) led to more specific results; however, confirmation is as yet mostly lacking. Systematic genome-wide linkage scans based on families with at least two individuals with an eating disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4 (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region led to the (as yet unconfirmed) identification of certain variants associated with AN. Genome-wide association studies are under way and will presumably help to identify genes and pathways involved in these eating disorders. The elucidation of the molecular mechanisms underlying eating disorders might improve therapeutic approaches.", "author" : [ { "dropping-particle" : "", "family" : "Scherag", "given" : "Susann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European and Child and Adolescent Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "211-216", "title" : "Eating disorders: the current status of molecular genetic research", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Scherag et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Scherag et al. 2010). Furthermore, there is evidence that people suffering from and who have recovered from AN have a reduced ability to experience reward, specifically in the context of food. Though anhedonia, a decreased ability to experience pleasure ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.apnu.2013.02.001", "ISSN" : "1532-8228", "PMID" : "23706888", "abstract" : "Anhedonia presents itself in a myriad of disease processes. To further develop our understanding of anhedonia and effective ways to manage it, the concept requires clear boundaries. This paper critically examined the current scientific literature and conducted a concept analysis of anhedonia to provide a more accurate and lucid understanding of the concept. As part of the concept analysis, this paper also provides model, borderline, related, and contrary examples of anhedonia.", "author" : [ { "dropping-particle" : "", "family" : "Ho", "given" : "Nancy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sommers", "given" : "Marilyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of Psychiatric Nursing", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "121-239", "publisher" : "Elsevier Inc.", "title" : "Anhedonia: a concept analysis", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "(Ho and Sommers, 2013)", "previouslyFormattedCitation" : "(Ho and Sommers 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Ho and Sommers, 2013) is often cited as the reason for decreased pleasure from food in people with AN, there is also the possibility of reward contamination ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neuropsychologia.2012.01.036", "ISSN" : "1873-3514", "PMID" : "22349445", "abstract" : "Individuals with anorexia nervosa (AN) demonstrate a relentless engagement in behaviors aimed to reduce their weight, which leads to severe underweight status, and occasionally death. Neurobiological abnormalities, as a consequence of starvation are controversial: evidence, however, demonstrates abnormalities in the reward system of patients, and recovered individuals. Despite this, a unifying explanation for reward abnormalities observed in AN and their relevance to symptoms of the illness, remains incompletely understood. Theories explaining reward dysfunction have conventionally focused on anhedonia, describing that patients have an impaired ability to experience reward or pleasure. We review taste reward literature and propose that patients' reduced responses to conventional taste-reward tasks may reflect a fear of weight gain associated with the caloric nature of the tasks, rather than an impaired ability to experience reward. Consistent with this, we propose that patients are capable of 'liking' hedonic taste stimuli (e.g., identifying them), however, they do not 'want' or feel motivated for the stimuli in the same way that healthy controls report. Recent brain imaging data on more complex reward processing tasks provide insights into fronto-striatal neural circuit dysfunction related to altered reward processing in AN that challenges the relevance of anhedonia in explaining reward dysfunction in AN. In this way, altered activity of the anterior cingulate cortex and striatum could explain patients' pathological engagement in behaviors they consider rewarding (e.g., self-starvation) that are otherwise aversive or punishing, to those without the eating disorder. Such evidence for altered patterns of brain activity associated with reward processing tasks in patients and recovered individuals may provide important information about mechanisms underlying symptoms of AN, their future investigation, and the development of treatment approaches.", "author" : [ { "dropping-particle" : "", "family" : "Keating", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tilbrook", "given" : "Alan J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossell", "given" : "Susan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Enticott", "given" : "Peter G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fitzgerald", "given" : "Paul B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuropsychologia", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "4" ] ] }, "page" : "567-575", "publisher" : "Elsevier Ltd", "title" : "Reward processing in anorexia nervosa", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keating et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keating et al. 2012). The theory of reward contamination stems from people suffering from eating disorders originally gaining pleasure from losing weight and practicing weight loss activities which then contaminates the usual reward responses, ultimately causing a neural overlap in circuits processing reward and punishment making it difficult for people to correctly regulate their behaviour ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neubiorev.2009.07.004", "ISSN" : "1873-7528", "PMID" : "19619579", "abstract" : "This theoretical proposal presents a revised framework for the role of reward in anorexia nervosa (AN). AN is associated with a fear of weight gain and refusal to maintain a minimally normal body weight. Up to 80% of patients engage in excessive exercise, in addition to self-starvation, to reduce their body weight. Anhedonia is the reduced ability to experience reward and is considered a feature of AN. Reward has been linked to reduced food intake and excessive exercise. This proposal portends that whilst patients' pathological behaviors are in the first instance, rewarding, they become reinforced in a manner that becomes pathological, even punishing. Patients, however, may not recognize that they are contaminating aspects of reward with punishment, which may impair their ability to regulate their behaviors. Neural overlap between circuits that process reward and those that process punishment, is proposed as a mechanism in AN, in addition to which the anterior cingulate cortex, may represent a key locus for reward-contamination.", "author" : [ { "dropping-particle" : "", "family" : "Keating", "given" : "Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroscience and Biobehavioral Reviews", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2010", "1" ] ] }, "page" : "73-79", "title" : "Theoretical perspective on anorexia nervosa: the conflict of reward", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keating 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keating 2010).The association of SNPs related to the serotonin pathway with eating disorders is conflicted. The most promising polymorphism is within the 5-HT2A (5-hydroxytryptamine receptor 2A) receptor gene (1438G/A, A is risk allele). In a meta-analysis of 11 studies of individuals with AN, the odds ratio for having the disease if the risk allele (-1438A) is present is 1.22 (95% confidence interval: 1.09 to 1.35) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0021620849", "author" : [ { "dropping-particle" : "", "family" : "Martaskova", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slachtova", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemlink", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zahorakova", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papezova", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Folia Biolgica", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "192-197", "title" : "Polymorphisms in serotonin-related genes in anorexia nervosa. The first study in Czech population and meta-analyses with previously performed studies", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Martaskova et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Martaskova et al. 2009). However high between-study heterogeneity reduces the confidence in the statistically significant increase in risk ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.ejphar.2003.08.103", "ISSN" : "00142999", "author" : [ { "dropping-particle" : "", "family" : "Gorwood", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Pharmacology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003", "11", "7" ] ] }, "page" : "163-170", "title" : "The human genetics of anorexia nervosa", "type" : "article-journal", "volume" : "480" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1375/183242705774310114", "ISSN" : "1832-4274", "PMID" : "16212836", "abstract" : "Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "467-482", "title" : "Eating disorders: from twin studies to candidate genes and beyond", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gorwood 2003; Slof-Op \u2019t Landt et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gorwood 2003; Slof-Op ’t Landt et al. 2005). For the association of 1438G/A with BN, five of eight studies were not significant, two were positive indicating the A allele as the risk allele and one study indicated that the G allele is the risk allele ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Maj", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monteleone", "given" : "Palmiero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pharmacogenomics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1487", "title" : "Genetic susceptibility to eating disorders: associated polymorphisms and pharmacogenetic suggestions", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Maj and Monteleone 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Maj and Monteleone 2008). To our knowledge, no studies have investigated the association of 5-HT2A with BED. 5-HT2A is regulated by estrogen which provides biological support for the association of 5-HT2A and eating disorders, particularly AN, because eating disorders are significantly more prevalent in females than males and in females usually begin at the time of puberty (Frank et al 2002, Kaye et al 2001). Further evidence comes from a study indicating that people currently suffering from or who have recovered from AN have reduced binding of 5-HT2A ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.tins.2013.01.003", "ISSN" : "1878-108X", "PMID" : "23333342", "abstract" : "Individuals with anorexia nervosa (AN) engage in relentless restrictive eating and often become severely emaciated. Because there are no proven treatments, AN has high rates of relapse, chronicity, and death. Those with AN tend to have childhood temperament and personality traits, such as anxiety, obsessions, and perfectionism, which may reflect neurobiological risk factors for developing AN. Restricted eating may be a means of reducing negative mood caused by skewed interactions between serotonin aversive or inhibitory and dopamine reward systems. Brain imaging studies suggest that altered eating is a consequence of dysregulated reward and/or awareness of homeostatic needs, perhaps related to enhanced executive ability to inhibit incentive motivational drives. An understanding of the neurobiology of this disorder is likely to be important for developing more effective treatments.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "Walter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierenga", "given" : "Christina E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simmons", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bischoff-Grethe", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Trends in Neurosciences", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "110-120", "publisher" : "Elsevier Ltd", "title" : "Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2013). 5-HTTLPR (serotonin-transporter-linked polymorphic region), the promoter region of the serotonin transporter coded by the SLC64A gene has provided some promising results in relation to eating disorders. Individuals either have the short allele (S) with only 14 repeats of a sequence versus those with the long allele (L) with 16 repeats. Carriers of the short allele only make half as much of the serotonin transporter protein as those with the long allele ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev-clinpsy-050212-185546", "ISSN" : "1548-5951", "PMID" : "23537489", "abstract" : "Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.", "author" : [ { "dropping-particle" : "", "family" : "Trace", "given" : "Sara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Jessica H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pe\u00f1as-Lled\u00f3", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Clinical Psychology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "589-620", "title" : "The genetics of eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Trace et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Trace et al. 2013). A meta-analysis using a random effects model of eight independent samples of individuals with AN provided a z-score of 2.54 (p=0.1) for having the S-containing genotype versus the L/L genotype ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.20811", "ISSN" : "1098-108X", "PMID" : "20209488", "abstract" : "OBJECTIVE: Eating disorders are influenced by both environmental factors and genes. The 5-HTTLPR polymorphism of serotonin transporter gene has been suggested as a good candidate. This meta-analysis was undertaken: (1) to investigate the association between 5-HTTLPR and eating disorders considered as a whole, including anorexia (AN), bulimia (BN), and binge eating disorder (BED); (2) to extend recently reported findings on the association between 5-HTTLPR and AN-BN. METHOD: PubMed, ISI, and PsycINFO databases were searched for studies published until October 2009. Fifteen studies have been included. Data were analyzed with the Cochrane Collaboration Review Manager Software. Quality of studies and publication bias were assessed. RESULTS: An association between S allele and eating disorders, in particular AN, has been found. DISCUSSION: To be carrier of the 5-HTTLPR S allele seem to represent a risk factor for eating disorders, especially for AN. However, considering the reported high between-study heterogeneity, future studies should focus on more homogeneous endophenotype.", "author" : [ { "dropping-particle" : "", "family" : "Calati", "given" : "Raffaella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ronchi", "given" : "Diana", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellini", "given" : "Maurizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serretti", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "4" ] ] }, "page" : "191-199", "title" : "The 5-HTTLPR polymorphism and eating disorders: a meta-analysis", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Calati et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Calati et al. 2011), similar results to an earlier meta-analysis involving four studies which found an odds ratio of 1.38 (95% confidence interval: 1.16 to 1.72) for people with the short allele variant compared to the long allele variant ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gorwood", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Pharmacogenomics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "9-17", "title" : "Eating disorders, serotonin transporter polymorphisms and potential treatment response", "type" : "article-journal", "volume" : "4" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gorwood 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gorwood 2004). In a meta-analysis of individuals from 6 studies with BN, the results were non-significant ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/YPG.0b013e32835669b3", "ISSN" : "1473-5873", "PMID" : "22815058", "abstract" : "Several lines of research have found that genes in the serotonergic system may cause susceptibility to eating disorders (EDs). In particular, functional polymorphisms of the serotonin transporter gene (5-HTT) have been suspected to play a role in the pathogenesis of eating disorders. Several studies have examined the association between the 5-HTTLPR polymorphism and bulimia nervosa (BN). The results of these investigations have been unclear. The aims of this meta-analysis were to clarify the association between BN and 5-HTTLPR using statistical models not used by previous meta-analyses, and extend upon previous meta-analyses by including new samples. PsychINFO, ISI, and PubMed databases were searched for studies published up to May 2011. Ultimately, six case-control samples were included. Data were pooled using dominant and additive models. Both models showed a nonsignificant association between the 5-HTTLPR polymorphism and BN. However, this does not detract from recent research suggesting that the 5-HTTLPR polymorphism may be responsible for the phenotypic variability in the psychopathological symptoms observed in patients with BN. Future research should examine the association of BN with 5-HTTLPR using the recently proposed triallelic model.", "author" : [ { "dropping-particle" : "", "family" : "Polsinelli", "given" : "Gina N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levitan", "given" : "Robert N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luca", "given" : "Vincenzo", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatric Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "10" ] ] }, "page" : "219-225", "title" : "5-HTTLPR polymorphism in bulimia nervosa: a multiple-model meta-analysis", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Polsinelli et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Polsinelli et al. 2012) with ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.20811", "ISSN" : "1098-108X", "PMID" : "20209488", "abstract" : "OBJECTIVE: Eating disorders are influenced by both environmental factors and genes. The 5-HTTLPR polymorphism of serotonin transporter gene has been suggested as a good candidate. This meta-analysis was undertaken: (1) to investigate the association between 5-HTTLPR and eating disorders considered as a whole, including anorexia (AN), bulimia (BN), and binge eating disorder (BED); (2) to extend recently reported findings on the association between 5-HTTLPR and AN-BN. METHOD: PubMed, ISI, and PsycINFO databases were searched for studies published until October 2009. Fifteen studies have been included. Data were analyzed with the Cochrane Collaboration Review Manager Software. Quality of studies and publication bias were assessed. RESULTS: An association between S allele and eating disorders, in particular AN, has been found. DISCUSSION: To be carrier of the 5-HTTLPR S allele seem to represent a risk factor for eating disorders, especially for AN. However, considering the reported high between-study heterogeneity, future studies should focus on more homogeneous endophenotype.", "author" : [ { "dropping-particle" : "", "family" : "Calati", "given" : "Raffaella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ronchi", "given" : "Diana", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellini", "given" : "Maurizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Serretti", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "4" ] ] }, "page" : "191-199", "title" : "The 5-HTTLPR polymorphism and eating disorders: a meta-analysis", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Calati et al. (2011)", "previouslyFormattedCitation" : "(Calati et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Calati et al. (2011) concluding that there was no significant difference in the occurrence of the S-containing genotype versus the L/L genotype in BN patients from 7 studies. Interestingly, there is a relationship between 5-HTTLPR and the development of BN in individuals who already have AN indicating the possibility of differences within the eating disorder population based on impulse control ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00213-007-0896-7", "ISSN" : "0033-3158", "PMID" : "17690869", "abstract" : "RATIONALE: Several lines of evidence suggest that altered serotonin (5-HT) function persists after recovery from anorexia nervosa (AN) and bulimia nervosa (BN). OBJECTIVES: We compared 11 subjects who recovered (>1 year normal weight, regular menstrual cycles, no binging or purging) from restricting-type AN (REC RAN), 7 who recovered from bulimia-type AN (REC BAN), 9 who recovered from BN (REC BN), and 10 healthy control women (CW). MATERIALS AND METHODS: Positron emission tomography (PET) imaging with [11C]McN5652 was used to assess the 5-HT transporter (5-HTT). For [11C]McN5652, distribution volume (DV) values were determined using a two-compartment, three-parameter tracer kinetic model, and specific binding was assessed using the binding potential (BP, BP=DVregion of interest/DVcerebellum-1). RESULTS: After correction for multiple comparisons, the four groups showed significant (p<0.05) differences for [11C]McN5652 BP values for the dorsal raphe and antero-ventral striatum (AVS). Post-hoc analysis revealed that REC RAN had significantly increased [11C]McN5652 BP compared to REC BAN in these regions. CONCLUSIONS: Divergent 5-HTT activity in subtypes of eating disorder subjects may provide important insights as to why these groups have differences in affective regulation and impulse control.", "author" : [ { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frank", "given" : "Guido K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henry", "given" : "Shannan E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Julie C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meltzer", "given" : "Carolyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Carl", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ziolko", "given" : "Scott K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mathis", "given" : "Chester a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barbarich-Marsteller", "given" : "Nicole C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Putnam", "given" : "Karen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "Walter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychopharmacology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007", "12" ] ] }, "page" : "315-324", "title" : "Serotonin transporter binding after recovery from eating disorders", "type" : "article-journal", "volume" : "195" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/ajmg.b.32052", "ISSN" : "1552-485X", "PMID" : "22488946", "abstract" : "Eating disorder patients show different long-term outcomes, and trait-related alterations of serotonergic function, which might be related with the serotonin transporter (5-HTT) gene. We studied the relationships between 5-HTTLPR polymorphism, eating specific and general psychopathology and the long-term outcome of anorexia nervosa (AN) and bulimia nervosa (BN) patients. We evaluated the distribution of the functional 5-HTTLPR polymorphism in a series of 201 Italian, Caucasian, eating disorder patients (113 with AN and 88 with BN binge/purging (BP subtype) and in 150 Caucasian unrelated controls. Prior to starting an individual cognitive behavior therapy, a clinical assessment was performed by means of the structured clinical interview for DSM-IV axis I disorders and several self-report questionnaires. This assessment was repeated at the end of treatment, 3 years after the end of treatment and 3 years after the first follow-up. Diagnostic changes between AN and BN were frequent (28.3%), and the presence of depressive disorders was associated with a higher rate of diagnostic crossover during the follow-up period. The S-allele of the 5-HTTLPR genotype increases the risk susceptibility for both depressive comorbidity (OR = 4.23; 95% CI, 1.45-12.37) and diagnostic crossover during the follow-up period in AN patients (OR = 5.04; 95% CI, 1.69-14.98). Logistic regression analyses confirmed these findings, when the interaction between genotype and psychiatric comorbidity as predictors of diagnostic instability in AN patients were taken into account. No significant association was found between 5-HTTLPR genotype and recovery. The S-allele of the 5-HTTLPR genotype increases the risk for depressive disorders comorbidity, and moderates the long-term outcome of anorectic patients.", "author" : [ { "dropping-particle" : "", "family" : "Castellini", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ricca", "given" : "Valdo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lelli", "given" : "Lorenzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bagnoli", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lucenteforte", "given" : "Ersilia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faravelli", "given" : "Carlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorbi", "given" : "Sandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nacmias", "given" : "Benedetta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Medical Genetics", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2012", "7" ] ] }, "page" : "491-500", "title" : "Association between serotonin transporter gene polymorphism and eating disorders outcome: a 6-year follow-up study.", "type" : "article-journal", "volume" : "159B" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1146/annurev-clinpsy-050212-185546", "ISSN" : "1548-5951", "PMID" : "23537489", "abstract" : "Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.", "author" : [ { "dropping-particle" : "", "family" : "Trace", "given" : "Sara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Jessica H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pe\u00f1as-Lled\u00f3", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Clinical Psychology", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "589-620", "title" : "The genetics of eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bailer et al. 2007; Castellini et al. 2012; Trace et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bailer et al. 2007; Castellini et al. 2012; Trace et al. 2013). To our knowledge, no studies have investigated the association of 5-HTTLPR with BED, however ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jpsychires.2011.09.013", "ISSN" : "1879-1379", "PMID" : "22018958", "abstract" : "Adverse life events have been shown to predict weight fluctuations and dietary restraint, as well as eating disorders during adolescence or early adulthood. Since the s-allele carriers of the 5-HTT gene-linked polymorphic region (5-HTTLPR) are biologically more reactive to stress related stimuli, we aimed to explore whether the eating disturbances are predicted by environmental stressors and moderated by the 5-HTTLPR genotype. The sample was based on the younger cohort of the Estonian Children Personality, Behaviour and Health Study and included those participating in its second and third wave. The history of stressful life events was self-reported at age 15. Data on eating behaviour and attitudes, anxiety, impulsivity and depressiveness were collected at age 18. The effect of the adverse life events on binge eating and on drive for thinness was found to be moderated by the 5-HTTLPR. Adolescent girls who at age 15 had reported a history of frequent adverse life events had elevated scores in EDI-2 Bulimia subscale at age 18 if they were carrying the s-allele. The effect of the s-allele on binge eating was even more pronounced when solely the experience of sexual abuse was considered. The interaction effect of the 5-HTTLPR and the past sexual abuse was also observed on drive for thinness. These data give further support to the idea that adverse life events in childhood may heighten susceptibility to serotonergic dysregulation following stress, and suggest that in individuals vulnerable to eating disorders this may result in disturbed eating behaviours.", "author" : [ { "dropping-particle" : "", "family" : "Akkermann", "given" : "Kirsti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaasik", "given" : "Kadri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiive", "given" : "Evelyn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nordquist", "given" : "Niklas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oreland", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harro", "given" : "Jaanus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "38-43", "publisher" : "Elsevier Ltd", "title" : "The impact of adverse life events and the serotonin transporter gene promoter polymorphism on the development of eating disorder symptoms.", "type" : "article-journal", "volume" : "46" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Akkermann et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Akkermann et al. 2012) determined that the 5-HTTLPR risk allele interacted with adverse life events in 18 year olds to increase the risk of binge eating indicating there may be some effect. Other serotonin receptors including the 5HT1B, 5HT1DB, 5HT2C, 5HTR3B, 5-HT3B, 5-HT1D, and 5HT7, and the enzymes tryptophan hydroxylase (TPH) responsible for the synthesis of serotonin, and monoamine oxidase A (MAOA) which breaks down serotonin have been studied in relation to eating disorders. However, the studies investigating these receptors and enzymes in the context of their association with eating disorders is limited and inconclusive at this point in time ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.brainresrev.2009.10.007", "ISSN" : "1872-6321", "PMID" : "19931559", "abstract" : "Anorexia nervosa (AN) is a complex multi-factorial disease with high heritability. The psychological AN symptoms are poorly connected with specific molecular mechanisms. Here we review the molecular basis of AN with the focus on human genetic association studies; we put these in the experimental biological context with emphasis on molecular systems controlling food intake and body weight in a direct or indirect manner. We systematically searched for human genetic studies related to AN and grouped data into main categories/systems reflecting their major known roles: (1) Systems related to mental disorders (serotonin, brain-derived neurotrophic factor (BDNF), norepinephrine (NE), glutamate (NMDA) receptor and SK3 channel, KCCN3). (2) Hunger regulatory systems (leptin, AGRP, MSH, melanocortin 4 receptor (MC4R), NPY, ghrelin, cholecystokinin (CCK). (3) Feeding motivation- and reward-related systems (opioids, OPRD1, cannabinoids (anandamide (AEA), THC, CBR1), dopamine, DRD2, DRD3, DRD4, catecholamine-O-methyl transferase (COMT). (4) Systems regulating energy metabolism (uncoupling proteins 2 and 3 (UCP2 and UCP3). (5) Neuroendocrine systems with emphasis on sex hormones (estrogen receptor-beta (ESR2). (6) The immune system and inflammatory response (tumor necrosis factor-alpha (TNF-alpha)). Overall, we found that in total 175 association studies have been performed on AN cohorts on 128 different polymorphisms related to 43 genes. We review the strongest associations, identify some genes that have an important role in regulating BMI whose possible relationship to AN has not been investigated and discuss the potential targets for pharmacological interventions.", "author" : [ { "dropping-particle" : "", "family" : "Rask-Andersen", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olszewski", "given" : "Pawel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Allen S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f6th", "given" : "Helgi B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain Research Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "147-164", "publisher" : "Elsevier B.V.", "title" : "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00787-009-0085-9", "ISSN" : "1435-165X", "PMID" : "20033240", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders characterized by disordered eating behavior where the patient's attitude towards weight and shape, as well as their perception of body shape, are disturbed. Formal genetic studies on twins and families suggested a substantial genetic influence for AN and BN. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Hardly any of the positive findings achieved in these studies were unequivocally confirmed or substantiated in meta-analyses. This might be due to too small sample sizes and thus low power and/or the genes underlying eating disorders have not yet been analyzed. However, some studies that also used subphenotypes (e.g., restricting type of AN) led to more specific results; however, confirmation is as yet mostly lacking. Systematic genome-wide linkage scans based on families with at least two individuals with an eating disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4 (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region led to the (as yet unconfirmed) identification of certain variants associated with AN. Genome-wide association studies are under way and will presumably help to identify genes and pathways involved in these eating disorders. The elucidation of the molecular mechanisms underlying eating disorders might improve therapeutic approaches.", "author" : [ { "dropping-particle" : "", "family" : "Scherag", "given" : "Susann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European and Child and Adolescent Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "211-216", "title" : "Eating disorders: the current status of molecular genetic research", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1146/annurev-clinpsy-050212-185546", "ISSN" : "1548-5951", "PMID" : "23537489", "abstract" : "Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.", "author" : [ { "dropping-particle" : "", "family" : "Trace", "given" : "Sara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Jessica H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pe\u00f1as-Lled\u00f3", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Clinical Psychology", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "589-620", "title" : "The genetics of eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rask-Andersen et al. 2010; Scherag et al. 2010; Trace et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rask-Andersen et al. 2010; Scherag et al. 2010; Trace et al. 2013). 2.7.2 Catecholamine pathwayThe main neurotransmitters involved in the catecholamine pathway are dopamine and norepinephrine ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.brainresrev.2009.10.007", "ISSN" : "1872-6321", "PMID" : "19931559", "abstract" : "Anorexia nervosa (AN) is a complex multi-factorial disease with high heritability. The psychological AN symptoms are poorly connected with specific molecular mechanisms. Here we review the molecular basis of AN with the focus on human genetic association studies; we put these in the experimental biological context with emphasis on molecular systems controlling food intake and body weight in a direct or indirect manner. We systematically searched for human genetic studies related to AN and grouped data into main categories/systems reflecting their major known roles: (1) Systems related to mental disorders (serotonin, brain-derived neurotrophic factor (BDNF), norepinephrine (NE), glutamate (NMDA) receptor and SK3 channel, KCCN3). (2) Hunger regulatory systems (leptin, AGRP, MSH, melanocortin 4 receptor (MC4R), NPY, ghrelin, cholecystokinin (CCK). (3) Feeding motivation- and reward-related systems (opioids, OPRD1, cannabinoids (anandamide (AEA), THC, CBR1), dopamine, DRD2, DRD3, DRD4, catecholamine-O-methyl transferase (COMT). (4) Systems regulating energy metabolism (uncoupling proteins 2 and 3 (UCP2 and UCP3). (5) Neuroendocrine systems with emphasis on sex hormones (estrogen receptor-beta (ESR2). (6) The immune system and inflammatory response (tumor necrosis factor-alpha (TNF-alpha)). Overall, we found that in total 175 association studies have been performed on AN cohorts on 128 different polymorphisms related to 43 genes. We review the strongest associations, identify some genes that have an important role in regulating BMI whose possible relationship to AN has not been investigated and discuss the potential targets for pharmacological interventions.", "author" : [ { "dropping-particle" : "", "family" : "Rask-Andersen", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olszewski", "given" : "Pawel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Allen S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f6th", "given" : "Helgi B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain Research Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "147-164", "publisher" : "Elsevier B.V.", "title" : "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3389/fncir.2013.00152", "ISSN" : "1662-5110", "PMID" : "24130517", "abstract" : "Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.", "author" : [ { "dropping-particle" : "", "family" : "Baik", "given" : "Ja-Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers in Neural Circuits", "id" : "ITEM-2", "issue" : "152", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "title" : "Dopamine signaling in reward-related behaviors", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rask-Andersen et al. 2010; Baik 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rask-Andersen et al. 2010; Baik 2013). Dopamine is the primary catecholamine neurotransmitter found in the brain and affects physiological functions such as motor activity, hormone secretion, motivation, and emotional behaviours ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fncir.2013.00152", "ISSN" : "1662-5110", "PMID" : "24130517", "abstract" : "Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.", "author" : [ { "dropping-particle" : "", "family" : "Baik", "given" : "Ja-Hyun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers in Neural Circuits", "id" : "ITEM-1", "issue" : "152", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "title" : "Dopamine signaling in reward-related behaviors", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1146/annurev-clinpsy-050212-185546", "ISSN" : "1548-5951", "PMID" : "23537489", "abstract" : "Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.", "author" : [ { "dropping-particle" : "", "family" : "Trace", "given" : "Sara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Jessica H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pe\u00f1as-Lled\u00f3", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Clinical Psychology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "589-620", "title" : "The genetics of eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Baik 2013; Trace et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Baik 2013; Trace et al. 2013). In the context of eating disorders, it is theorized that increased dopamine activity is associated with symptoms such as weight loss, altered satiety, impulse control, mood, hyperactivity, amenorrhea, body image distortion, and obsessive-compulsive behaviour ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.tins.2013.01.003", "ISSN" : "1878-108X", "PMID" : "23333342", "abstract" : "Individuals with anorexia nervosa (AN) engage in relentless restrictive eating and often become severely emaciated. Because there are no proven treatments, AN has high rates of relapse, chronicity, and death. Those with AN tend to have childhood temperament and personality traits, such as anxiety, obsessions, and perfectionism, which may reflect neurobiological risk factors for developing AN. Restricted eating may be a means of reducing negative mood caused by skewed interactions between serotonin aversive or inhibitory and dopamine reward systems. Brain imaging studies suggest that altered eating is a consequence of dysregulated reward and/or awareness of homeostatic needs, perhaps related to enhanced executive ability to inhibit incentive motivational drives. An understanding of the neurobiology of this disorder is likely to be important for developing more effective treatments.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "Walter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierenga", "given" : "Christina E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simmons", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bischoff-Grethe", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Trends in Neurosciences", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "110-120", "publisher" : "Elsevier Ltd", "title" : "Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1146/annurev-clinpsy-050212-185546", "ISSN" : "1548-5951", "PMID" : "23537489", "abstract" : "Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.", "author" : [ { "dropping-particle" : "", "family" : "Trace", "given" : "Sara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Jessica H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pe\u00f1as-Lled\u00f3", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Clinical Psychology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "589-620", "title" : "The genetics of eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2013; Trace et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2013; Trace et al. 2013). Two main theories similar to those for serotonin exist on how dopamine may play a role in the development of AN. The first is that dieting and exercise are initially rewarding behaviours and as time progresses the behaviour is maintained through conditioning ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2010.03.016", "ISSN" : "1873-507X", "PMID" : "20361989", "abstract" : "Restricted food intake is associated with increased physical activity, very likely an evolutionary advantage, initially both functional and rewarding. The hyperactivity of patients with anorexia nervosa, however, is a main problem for recovery. This seemingly paradoxical reward of hyperactivity in anorexia nervosa is one of the main aspects in our framework for the neurobiological changes that may underlie the development of the disorder. Here, we focus on the neurobiological basis of hyperactivity and reward in both animals and humans suggesting that the mesolimbic dopamine and hypothalamic orexin neurons play central roles. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.", "author" : [ { "dropping-particle" : "", "family" : "Scheurink", "given" : "Anton J W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boersma", "given" : "Gretha J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nerg\u00e5rdh", "given" : "Ricard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f6dersten", "given" : "Per", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & Behavior", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2010", "7", "14" ] ] }, "page" : "490-495", "publisher" : "Elsevier Inc.", "title" : "Neurobiology of hyperactivity and reward: agreeable restlessness in anorexia nervosa", "type" : "article-journal", "volume" : "100" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Scheurink et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Scheurink et al. 2010), and the second is that people with AN have reduced food consumption because they do not receive pleasure from food ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/FBP.0b013e328357e115", "ISSN" : "1473-5849", "PMID" : "22854306", "abstract" : "Anorexia nervosa (AN) is a chronic relapsing psychiatric disorder with a largely unknown pathophysiology. Dopamine has been implicated in the pathophysiology of the disorder by preclinical and clinical evidence. Preclinical studies have examined two main characteristics of AN: reduction in food intake (diet restriction) and hyperactivity. Diet restriction has been associated with reduced dopamine levels in the hypothalamus, hippocampus, and the dorsal striatum. Animal hyperactivity following diet restriction has been linked to increased dopamine in the hypothalamus. Increased dopamine in the nucleus accumbens was associated with food administration, but not food expectation. Tyrosine and dopaminergic antagonists normalized anorexia-like behaviors in animal models of AN, but did not restore body weight. Clinical studies on the etiology of AN have produced contradictory findings. Cerebrospinal fluid concentrations of dopamine and its metabolites have been reported to be decreased or normal under conditions of low weight, whereas they tended to normalize when the weight was restored. Plasma and urinary levels of dopamine and its metabolites have been found to be normal, increased, and decreased. Neuroendocrine studies suggest that dopaminergic neurotransmission is increased in AN. However, recent neuroimaging studies lend support to the increase in binding of dopaminergic receptors in the striatum, which favors the opposite theory that intrasynaptic dopamine is indeed decreased. Genetic studies implicate dopamine D2 receptors, the dopamine transporter, and the enzyme COMT. There are promising results with respect to the use of atypical antipsychotics against symptoms of AN beyond weight gain, but further trials are required.", "author" : [ { "dropping-particle" : "", "family" : "Kontis", "given" : "Dimitrios", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Theochari", "given" : "Eirini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Behavioural Pharmacology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "page" : "496-515", "title" : "Dopamine in anorexia nervosa: a systematic review", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kontis and Theochari 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kontis and Theochari 2012). The effects of dopamine may be different in BN and BED. Blocking dopamine receptors has been found to increase appetite and cause weight gain, therefore overeating during binge periods may be a compensation method for the blunting of the pleasurable response to eating ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/10550490903205579", "ISBN" : "1055049090320", "ISSN" : "1521-0391", "PMID" : "19874165", "abstract" : "Obesity is a major public health problem and notoriously difficult to treat. There are many parallels between obesity/overeating and addictions to alcohol and drugs. This paper discusses similarities between obesity and addictive disorders, including common personality characteristics, disruptive behavior syndromes, and brain mechanisms. Although there are important differences between overeating and other addictive behaviors, an addiction model of overeating may effectively inform prevention and treatment of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Barry", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Megan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petry", "given" : "Nancy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal on Additions", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "439-451", "title" : "Obesity and its relationship to addictions: is overeating a form of addictive behavior?", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Barry et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Barry et al. 2009). Severely obese individuals have been found to have fewer striatal dopamine receptors compared to normal weight people with a decrease in the number of dopamine receptors as weight increases ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0140-6736", "PMID" : "11210998", "abstract" : "BACKGROUND: The cerebral mechanisms underlying the behaviours that lead to pathological overeating and obesity are poorly understood. Dopamine, a neurotransmitter that modulates rewarding properties of food, is likely to be involved. To test the hypothesis that obese individuals have abnormalities in brain dopamine activity we measured the availability of dopamine D2 receptors in brain. METHODS: Brain dopamine D2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy-2[18F]fluoro-D-glucose (FDG). FINDINGS: Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p < or = 0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0.84; p < or = 0.002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer delivery. INTERPRETATION: The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits. Strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals.", "author" : [ { "dropping-particle" : "", "family" : "Wang", "given" : "G J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Volkow", "given" : "N D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Logan", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pappas", "given" : "N R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wong", "given" : "C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhu", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Netusil", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fowler", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9253", "issued" : { "date-parts" : [ [ "2001", "2", "3" ] ] }, "page" : "354-357", "title" : "Brain dopamine and obesity", "type" : "article-journal", "volume" : "357" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wang et al. 2001)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wang et al. 2001). Therefore, overweight/obese people may binge on highly palatable and calorically dense foods which stimulate the greatest amount of dopamine activity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.neuron.2006.08.025", "ISSN" : "0896-6273", "PMID" : "16982416", "abstract" : "The past decade has witnessed dramatic advancements regarding the neuroendocrine control of food intake and energy homeostasis and the effects of peripheral metabolic signals on the brain. The development of molecular and genetic tools to visualize and selectively manipulate components of homeostatic systems, in combination with well-established neuroanatomical, electrophysiological, behavioral, and pharmacological techniques, are beginning to provide a clearer picture of the intricate circuits and mechanisms of these complex processes. In this review, we attempt to provide some highlights of these advancements and pinpoint some of the shortcomings of the current understanding of the brain's involvement in the regulation of daily energy homeostasis.", "author" : [ { "dropping-particle" : "", "family" : "Abizaid", "given" : "Alfonso", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gao", "given" : "Qian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horvath", "given" : "Tamas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuron", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2006", "9", "21" ] ] }, "page" : "691-702", "title" : "Thoughts for food: brain mechanisms and peripheral energy balance.", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Abizaid et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Abizaid et al. 2006). It is unknown at this time if low dopamine activity is the cause of overeating ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/10550490903205579", "ISBN" : "1055049090320", "ISSN" : "1521-0391", "PMID" : "19874165", "abstract" : "Obesity is a major public health problem and notoriously difficult to treat. There are many parallels between obesity/overeating and addictions to alcohol and drugs. This paper discusses similarities between obesity and addictive disorders, including common personality characteristics, disruptive behavior syndromes, and brain mechanisms. Although there are important differences between overeating and other addictive behaviors, an addiction model of overeating may effectively inform prevention and treatment of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Barry", "given" : "Danielle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "Megan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Petry", "given" : "Nancy M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal on Additions", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "439-451", "title" : "Obesity and its relationship to addictions: is overeating a form of addictive behavior?", "type" : "article-journal", "volume" : "18" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Barry et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Barry et al. 2009), or if overeating causes elevated dopamine levels leading to the down regulation of dopamine receptors ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1300/J069v23n03", "author" : [ { "dropping-particle" : "", "family" : "Wang", "given" : "Gene-jack", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Volkow", "given" : "Nora D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thanos", "given" : "Panayotis K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fowler", "given" : "Joanna S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Addictive Diseases", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "39-53", "title" : "Similarity between obesity and drug addiction as assessed by neurofunctional imaging", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wang et al. 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wang et al. 2004).SNPs involved with three dopamine receptors (D2, D3, and D4), a dopamine transporter (DAT1), as well as catecholamine-O-methyltransferase (COMT), an enzyme involved in monoamine metabolism, have been investigated for their association with eating disorders. Overall, the evidence is at best weak with more studies being conducted in people with AN than BN or BED. For DRD2 (dopamine receptor 2), a statistically significant relationship was found between DRD2 - +725 3’ G>T and TaqIA C>T with the purging subtype of AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/sj.npp.1300719", "ISSN" : "0893-133X", "PMID" : "15920508", "abstract" : "To investigate whether the dopaminergic system plays a role in the etiology of anorexia nervosa (AN) via the dopamine D2 receptor, we investigated association and transmission disequilibrium at seven single-nucleotide polymorphisms (SNPs) spanning about 75 kbp of the gene DRD2. We studied 191 probands with a DSM-IV diagnosis of AN, 457 parents and affected relatives with a DSM-IV eating disorder diagnosis, and 98 unrelated, female, normal weight controls. The -141 C/- insertion/deletion (-141 Indel), previously shown to affect DRD2 transcription efficiency, and multiple exon seven polymorphisms, one of which has previously been shown to affect DRD2 transcript stability, exhibited statistically significant association with diagnosis in haplotype transmission disequilibrium and in haplotype case : control analyses. Significant linkage disequilibrium between the -141 Indel and two exon seven SNPs (939Y and 957Y) was observed over a distance of >50 kbp in the AN probands but not in the controls. Genetically transmitted variation in D2 dopamine receptor expression mediated by functional polymorphisms affecting transcription and translation efficiency may play a role in vulnerability to AN.", "author" : [ { "dropping-particle" : "", "family" : "Bergen", "given" : "Andrew W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yeager", "given" : "Meredith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haque", "given" : "Kashif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ganjei", "given" : "J Kelly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bree", "given" : "Marianne B M", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mazzanti", "given" : "Chiara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nardi", "given" : "Irma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fichter", "given" : "Manfred M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halmi", "given" : "Katherine a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplan", "given" : "Allan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woodside", "given" : "D Blake", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacanu", "given" : "Silviu-Alin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devlin", "given" : "Bernie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berrettini", "given" : "Wade H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "Walter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuropsychopharmacology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005", "9" ] ] }, "page" : "1703-1710", "title" : "Association of multiple DRD2 polymorphisms with anorexia nervosa", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bergen et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bergen et al. 2005) as well as an association between rs1800497, rs2283265 and rs6277 (DRD2) with BED ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pnpbp.2012.05.002", "ISSN" : "1878-4216", "PMID" : "22579533", "abstract" : "OBJECTIVE: While the study of binge eating disorder (BED) has burgeoned in the past decade, an understanding of its neurobiological underpinnings is still in the early stages. Previous research suggests that BED may be an overeating syndrome characterized by a hyper-responsiveness to reward, and a strong dopamine signaling in the neuro-circuitry that regulates pleasure and appetitive behaviors. We investigated the D2 receptors genes (DRD2/ANKK1) and their relation to the BED phenotype and four sub-phenotypes of BED that reflect an enhanced response to positive food stimuli. METHODS: In a sample of 230 obese adults with and without BED, we genotyped five functional markers of the D2 receptor: rs1800497, rs1799732, rs2283265, rs12364283, and rs6277, and assessed binge eating, emotional eating, hedonic eating, and food craving from dimensionally-scored, self-report questionnaires. RESULTS: Compared to weight-matched controls, BED was significantly related to the rs1800497 and rs6277 genotypes that reflect enhanced dopamine neurotransmission. BED participants were also less likely to carry the minor T allele of rs2283265. The same markers related to the sub-phenotypes of BED with rs1800497 showing the strongest effects in the predicted direction. CONCLUSIONS: This study supports the view that BED may be a condition that has its causal origins in a hypersensitivity to reward - a predisposition that is likely to foster overeating in our current environment with abundant availability of highly palatable and calorically-dense processed foods.", "author" : [ { "dropping-particle" : "", "family" : "Davis", "given" : "Caroline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levitan", "given" : "Robert D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yilmaz", "given" : "Zeynep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplan", "given" : "Allan S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carter", "given" : "Jacqueline C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kennedy", "given" : "James L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Progress in Neuro-Psychopharmacology and Biological Psychiatry", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "8", "7" ] ] }, "page" : "328-335", "publisher" : "Elsevier Inc.", "title" : "Binge eating disorder and the dopamine D2 receptor: genotypes and sub-phenotypes", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Davis et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Davis et al. 2012). However, Nisoli et al (2007) did not find between group differences of TaqA1 C>T in those with AN, BN, those who are obese, and a control group, and Gervasini et al (2013) found no association between rs1800497 (DRD2) and AN. DRD3 has been less studied, however both ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/JCP.0b013e3182970469", "ISSN" : "1533-712X", "PMID" : "23775054", "abstract" : "Dopamine neuronal functions make polymorphisms in dopaminergic pathways good candidates for playing a relevant role in anorexia nervosa (AN) and related psychopathological features. We have analyzed the effect of 8 polymorphisms in genes coding for dopamine receptors (DRD2, DRD3, and DRD4), transporters (DAT1) and metabolizing enzymes (COMT) in 78 women with AN and 186 control subjects. Associated psychopathological characteristics in patients with AN were assessed by the Eating Disorders Inventory Test-2 and SCL-90R self-reported questionnaires. The DRD4 variable number of tandem repeats (VNTR) 7R/7R and DRD4 -616CC genotypes were significantly associated with a greater risk for AN (odds ratio, 3.83; confidence interval, 1.05-13.98; P = 0.04; and odds ratio, 1.74; confidence interval, 1.01-2.97; P = 0.03, respectively). The analysis of physiological parameters in the patients with AN revealed that the short allele of a 120-base pair tandem repeat in the promoter region of the DRD4 gene was associated with higher weight (48.35 \u00b1 6.79 vs 43.95 \u00b1 5.78 kg; Bonferroni, P < 0.05), whereas the DRD4 -521TT genotype was associated with significantly higher body mass index (17.29 \u00b1 2.25 vs 18.13 \u00b1 2.41 kg/m2; Bonferroni, P < 0.05). The DRD4 C-616G and DAT1 VNTR polymorphisms correlated with several psychopathological features in patients with AN. Carriers of the mutant homozygous genotypes scored higher in all but one of the Eating Disorders Inventory Test-2 subscales. After correction for multiple testing, differences in Asceticism scores between DAT1 VNTR genotypes, as well as differences in Drive for Thinness and Body Dissatisfaction between C-616G genotypes remained significant (P < 0.05). The results show that certain genetic alterations in the dopamine pathways are able to modify the risk for AN as well as modulate psychopathological features that are often coupled to this disorder.", "author" : [ { "dropping-particle" : "", "family" : "Gervasini", "given" : "Guillermo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordillo", "given" : "Inmaculada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Herr\u00e1iz", "given" : "Angustias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flores", "given" : "Isalud", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez", "given" : "Mercedes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monge", "given" : "Melchora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrillo", "given" : "Juan Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Psychopharmacology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "551-555", "title" : "Influence of dopamine polymorphisms on the risk for anorexia nervosa and associated psychopathological features", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Gervasini et al. (2013)", "previouslyFormattedCitation" : "(Gervasini et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Gervasini et al. (2013) and ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0006-3223", "PMID" : "9442347", "abstract" : "BACKGROUND: Evidence from family and twin studies suggests a genetic contribution to the etiology of anorexia nervosa. Different genes could contribute to the vulnerability to anorexia nervosa, but dopamine could be more specifically implicated in anorexia nervosa because of pharmacologic, endocrine, and neurobiological specificities. The dopamine receptor D3 (DRD3) may be of additional interest, since it is specifically located in the limbic area, an area implicated in reward and reinforcement behavior. METHODS: We performed an association study between 39 patients with severe (requiring hospitalization and with young age at onset) anorexia nervosa (DSM-III-R), and 42 controls, with the Bal I polymorphism in exon I of the DRD3 gene. RESULTS: There was no significant difference between patients with anorexia nervosa and controls in allele frequencies or genotype count. The association was still negative between subgroups separated according to family history of anorexia nervosa or comorbid mood disorders. CONCLUSIONS: Despite the fact that the number of patients tested is small, there is good evidence that the Bal I DRD3 polymorphism does not play a major role in the genetic component of anorexia nervosa. It would be useful to test polymorphisms of the other genes coding for dopamine receptors.", "author" : [ { "dropping-particle" : "", "family" : "Bruins-Slot", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorwood", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouvard", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blot", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ad\u00e8s", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feingold", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schwartz", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mouren-Sim\u00e9oni", "given" : "M C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1998", "1", "1" ] ] }, "page" : "76-78", "title" : "Lack of association between anorexia nervosa and D3 dopamine receptor gene", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Bruins-Slot et al. (1998)", "previouslyFormattedCitation" : "(Bruins-Slot et al. 1998)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Bruins-Slot et al. (1998) found no association between AN and the DRD3 Ser/Gly variant and DRD3 with Val1 polymorphism in exon 1 respectively. Two studies have found a positive association between DRD4 (7 repeat allele) and a greater risk of AN (OR=1.74, 95% CI 1.01 to 2.97) and BED (OR=3.25, 95%CI 1.43 to 7.41) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/JCP.0b013e3182970469", "ISSN" : "1533-712X", "PMID" : "23775054", "abstract" : "Dopamine neuronal functions make polymorphisms in dopaminergic pathways good candidates for playing a relevant role in anorexia nervosa (AN) and related psychopathological features. We have analyzed the effect of 8 polymorphisms in genes coding for dopamine receptors (DRD2, DRD3, and DRD4), transporters (DAT1) and metabolizing enzymes (COMT) in 78 women with AN and 186 control subjects. Associated psychopathological characteristics in patients with AN were assessed by the Eating Disorders Inventory Test-2 and SCL-90R self-reported questionnaires. The DRD4 variable number of tandem repeats (VNTR) 7R/7R and DRD4 -616CC genotypes were significantly associated with a greater risk for AN (odds ratio, 3.83; confidence interval, 1.05-13.98; P = 0.04; and odds ratio, 1.74; confidence interval, 1.01-2.97; P = 0.03, respectively). The analysis of physiological parameters in the patients with AN revealed that the short allele of a 120-base pair tandem repeat in the promoter region of the DRD4 gene was associated with higher weight (48.35 \u00b1 6.79 vs 43.95 \u00b1 5.78 kg; Bonferroni, P < 0.05), whereas the DRD4 -521TT genotype was associated with significantly higher body mass index (17.29 \u00b1 2.25 vs 18.13 \u00b1 2.41 kg/m2; Bonferroni, P < 0.05). The DRD4 C-616G and DAT1 VNTR polymorphisms correlated with several psychopathological features in patients with AN. Carriers of the mutant homozygous genotypes scored higher in all but one of the Eating Disorders Inventory Test-2 subscales. After correction for multiple testing, differences in Asceticism scores between DAT1 VNTR genotypes, as well as differences in Drive for Thinness and Body Dissatisfaction between C-616G genotypes remained significant (P < 0.05). The results show that certain genetic alterations in the dopamine pathways are able to modify the risk for AN as well as modulate psychopathological features that are often coupled to this disorder.", "author" : [ { "dropping-particle" : "", "family" : "Gervasini", "given" : "Guillermo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordillo", "given" : "Inmaculada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Herr\u00e1iz", "given" : "Angustias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flores", "given" : "Isalud", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez", "given" : "Mercedes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monge", "given" : "Melchora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrillo", "given" : "Juan Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Psychopharmacology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "551-555", "title" : "Influence of dopamine polymorphisms on the risk for anorexia nervosa and associated psychopathological features", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gervasini et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gervasini et al. 2013). Other positive results include an association between AN and DRD4-616C/C ( odds ratio: 3.83, 95% confidence interval: 1.05 to 13.98) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/JCP.0b013e3182970469", "ISSN" : "1533-712X", "PMID" : "23775054", "abstract" : "Dopamine neuronal functions make polymorphisms in dopaminergic pathways good candidates for playing a relevant role in anorexia nervosa (AN) and related psychopathological features. We have analyzed the effect of 8 polymorphisms in genes coding for dopamine receptors (DRD2, DRD3, and DRD4), transporters (DAT1) and metabolizing enzymes (COMT) in 78 women with AN and 186 control subjects. Associated psychopathological characteristics in patients with AN were assessed by the Eating Disorders Inventory Test-2 and SCL-90R self-reported questionnaires. The DRD4 variable number of tandem repeats (VNTR) 7R/7R and DRD4 -616CC genotypes were significantly associated with a greater risk for AN (odds ratio, 3.83; confidence interval, 1.05-13.98; P = 0.04; and odds ratio, 1.74; confidence interval, 1.01-2.97; P = 0.03, respectively). The analysis of physiological parameters in the patients with AN revealed that the short allele of a 120-base pair tandem repeat in the promoter region of the DRD4 gene was associated with higher weight (48.35 \u00b1 6.79 vs 43.95 \u00b1 5.78 kg; Bonferroni, P < 0.05), whereas the DRD4 -521TT genotype was associated with significantly higher body mass index (17.29 \u00b1 2.25 vs 18.13 \u00b1 2.41 kg/m2; Bonferroni, P < 0.05). The DRD4 C-616G and DAT1 VNTR polymorphisms correlated with several psychopathological features in patients with AN. Carriers of the mutant homozygous genotypes scored higher in all but one of the Eating Disorders Inventory Test-2 subscales. After correction for multiple testing, differences in Asceticism scores between DAT1 VNTR genotypes, as well as differences in Drive for Thinness and Body Dissatisfaction between C-616G genotypes remained significant (P < 0.05). The results show that certain genetic alterations in the dopamine pathways are able to modify the risk for AN as well as modulate psychopathological features that are often coupled to this disorder.", "author" : [ { "dropping-particle" : "", "family" : "Gervasini", "given" : "Guillermo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordillo", "given" : "Inmaculada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Herr\u00e1iz", "given" : "Angustias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flores", "given" : "Isalud", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez", "given" : "Mercedes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monge", "given" : "Melchora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrillo", "given" : "Juan Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Psychopharmacology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "551-555", "title" : "Influence of dopamine polymorphisms on the risk for anorexia nervosa and associated psychopathological features", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gervasini et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gervasini et al. 2013) and an association between DRD4 - C-521T’C’ allele and AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ajmg.b.30505", "ISSN" : "1552-4841", "PMID" : "17440932", "abstract" : "The dopamine D4 receptor (DRD4), a well-characterized, polymorphic gene, is an attractive candidate for contributing risk to disordered eating and anorexia nervosa (AN). We tested association using UNPHASED for 5 DRD4 polymorphic loci, 3 promoter region SNPs (C-521T, C-616G, A-809G), the 120 bp promoter region tandem duplication and the exon III repeat, in 202 AN trios and 418 control families. Since perfectionism characterizes AN, we tested these five loci for association with the Child and Adolescent Perfectionism Scale (CAPS) in the AN and control groups. Single locus analysis showed significant association between the 'C' C-521T allele and AN. Haplotype analysis also showed significant association, particularly a 4-locus haplotype (exon III&120 bp repeat&C-521T&A-809G). Association was also observed between DRD4 and CAPS scores both for AN and control subjects. The insulin-like growth factor 2 (IGF2) and the arginine vasopressin 1a receptor (AVPR1a), previously shown to be associated with disordered eating, were also associated with CAPS scores. Three genes associated with AN were also associated with perfectionism. Personality traits are potential endophenotypes for understanding the etiology of eating disorders and one of the several pathways to eating pathology may be mediated by the impact of DNA sequences on perfectionism.", "author" : [ { "dropping-particle" : "", "family" : "Bachner-Melman", "given" : "Rachel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lerer", "given" : "Elad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zohar", "given" : "Ada H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kremer", "given" : "Ilana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elizur", "given" : "Yoel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nemanov", "given" : "Lubov", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Golan", "given" : "Moria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blank", "given" : "Shulamit", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gritsenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebstein", "given" : "Richard P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Medical Genetics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007", "9", "5" ] ] }, "page" : "748-756", "title" : "Anorexia nervosa, perfectionism, and dopamine D4 receptor (DRD4)", "type" : "article-journal", "volume" : "144B" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bachner-Melman et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bachner-Melman et al. 2007). However two studies found no between group differences for DRD4 (13-bp and 48-bp deletion) in patients with AN, underweight students, and obese children/adolescents ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0148-7299", "PMID" : "10581473", "abstract" : "Family and twin studies suggest a genetic contribution to the etiology of anorexia nervosa (AN) and obesity. Genes involved in weight regulation can be considered as candidate genes for AN. The dopaminergic system has been implicated in weight regulation; previous results had suggested a possible involvement of the dopamine D4 receptor gene (DRD4). We screened for alleles of two different polymorphisms (13-bp deletion, 48-bp repeat) in the DRD4. For association tests, allele frequencies were compared between 109 inpatients with AN, 82 underweight students, and 327 extremely obese children and adolescents. For application of transmission disequlibrium tests (TDT) we additionally genotyped 57 and 137 trios comprising a patient with AN or an extremely obese child or adolescent, respectively, and both parents. All genotyping was performed with polymerase chain reaction fragment length polymorphism analyses. None of the association tests or TDT rendered nominal P values below 0.1. An influence of alleles of the DRD4 on the development of AN, underweight, or extreme early onset obesity was not detected. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:594-597, 1999.", "author" : [ { "dropping-particle" : "", "family" : "Hinney", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ziegler", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehmkuhl", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poustka", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "M H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayer", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siegfried", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Remschmidt", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Medical Genetics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1999", "12", "15" ] ] }, "page" : "594-597", "title" : "No evidence for involvement of polymorphisms of the dopamine D4 receptor gene in anorexia nervosa, underweight, and obesity", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hinney et al. 1999)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hinney et al. 1999) and DRD4 (22, 24, 33, 34, 44 repeats, 27, 37, 47 repeats, and 77 repeats) prevalence in female siblings, one with and one without AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0033-2917", "PMID" : "11232918", "abstract" : "BACKGROUND: The aim of this pilot study was to examine which unique factors (genetic and environmental) increase the risk for developing anorexia nervosa by using a case-control design of discordant sister pairs. METHODS: Forty-five sister-pairs, one of whom had anorexia nervosa and the other did not, were recruited. Both sisters completed the Oxford Risk Factor Interview for Eating Disorders and measures for eating disorder traits, and sib-pair differences. Blood or cheek cell samples were taken for genetic analysis. Statistical power of the genetic analysis of discordant same-sex siblings was calculated using a specially written program, DISCORD. RESULTS: The sisters with anorexia nervosa differed from their healthy sisters in terms of personal vulnerability traits and exposure to high parental expectations and sexual abuse. Factors within the dieting risk domain did not differ. However, there was evidence of poor feeding in childhood. No difference in the distribution of genotypes or alleles of the DRD4, COMT, the 5HT2A and 5HT2C receptor genes was detected. These results are preliminary because our calculations indicate that there is insufficient power to detect the expected effect on risk with this sample size. CONCLUSIONS: A combination of intrinsic and extrinsic factors increases the risk of developing anorexia nervosa. It would, therefore, be informative to undertake a larger study to examine in more detail the unique genetic and environmental factors that are associated with various forms of eating disorders.", "author" : [ { "dropping-particle" : "", "family" : "Karwautz", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rabe-Hesketh", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collier", "given" : "D a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "J L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2001", "2" ] ] }, "page" : "317-329", "title" : "Individual-specific risk factors for anorexia nervosa: a pilot study using a discordant sister-pair design", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Karwautz et al. 2001)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Karwautz et al. 2001). Only one study investigated DAT1 and AN and found no association ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/JCP.0b013e3182970469", "ISSN" : "1533-712X", "PMID" : "23775054", "abstract" : "Dopamine neuronal functions make polymorphisms in dopaminergic pathways good candidates for playing a relevant role in anorexia nervosa (AN) and related psychopathological features. We have analyzed the effect of 8 polymorphisms in genes coding for dopamine receptors (DRD2, DRD3, and DRD4), transporters (DAT1) and metabolizing enzymes (COMT) in 78 women with AN and 186 control subjects. Associated psychopathological characteristics in patients with AN were assessed by the Eating Disorders Inventory Test-2 and SCL-90R self-reported questionnaires. The DRD4 variable number of tandem repeats (VNTR) 7R/7R and DRD4 -616CC genotypes were significantly associated with a greater risk for AN (odds ratio, 3.83; confidence interval, 1.05-13.98; P = 0.04; and odds ratio, 1.74; confidence interval, 1.01-2.97; P = 0.03, respectively). The analysis of physiological parameters in the patients with AN revealed that the short allele of a 120-base pair tandem repeat in the promoter region of the DRD4 gene was associated with higher weight (48.35 \u00b1 6.79 vs 43.95 \u00b1 5.78 kg; Bonferroni, P < 0.05), whereas the DRD4 -521TT genotype was associated with significantly higher body mass index (17.29 \u00b1 2.25 vs 18.13 \u00b1 2.41 kg/m2; Bonferroni, P < 0.05). The DRD4 C-616G and DAT1 VNTR polymorphisms correlated with several psychopathological features in patients with AN. Carriers of the mutant homozygous genotypes scored higher in all but one of the Eating Disorders Inventory Test-2 subscales. After correction for multiple testing, differences in Asceticism scores between DAT1 VNTR genotypes, as well as differences in Drive for Thinness and Body Dissatisfaction between C-616G genotypes remained significant (P < 0.05). The results show that certain genetic alterations in the dopamine pathways are able to modify the risk for AN as well as modulate psychopathological features that are often coupled to this disorder.", "author" : [ { "dropping-particle" : "", "family" : "Gervasini", "given" : "Guillermo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordillo", "given" : "Inmaculada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Herr\u00e1iz", "given" : "Angustias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flores", "given" : "Isalud", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez", "given" : "Mercedes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monge", "given" : "Melchora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrillo", "given" : "Juan Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Psychopharmacology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "551-555", "title" : "Influence of dopamine polymorphisms on the risk for anorexia nervosa and associated psychopathological features", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gervasini et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gervasini et al. 2013). For COMT, only AN has been reasonably well studied, with a meta-analysis of COMT (rs4680) and AN including 11 datasets (2021 cases, 2848 controls, 89 informative trios) concluding there is no association and very little between study heterogeneity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/YPG.0b013e328351859e", "ISSN" : "1473-5873", "PMID" : "22366815", "abstract" : "OBJECTIVES: This study aimed to test the association between the Val158Met polymorphism (rs4680) of the catechol-O-methyl transferase gene and anorexia nervosa (AN). METHODS: First, an association study on two cohorts (306 cases and 1009 controls from Utrecht, and 174 cases and 466 controls from Leiden/NTR) was performed. Subsequently, the results were integrated into a meta-analysis, together with all the case-control and family-based studies, which were testing the same hypothesis and were available in the literature. Altogether, eight studies (11 datasets) were included in this meta-analysis, with a total of 2021 cases, 2848 controls, and 89 informative (heterozygous) trios. RESULTS: The present association studies found no association between AN and rs4680 when testing the allelic contrast [Utrecht odds ratio (OR)=1.14, P=0.14; Leiden OR=1.02, P=0.85]. There was an indication of an association under the dominant model of genetic effect in the Utrecht cohort (for the Met allele, OR=1.42, P=0.03). Nevertheless, the meta-analyses of both the allelic contrast and the dominant effect were nonsignificant (the allelic pooled OR=1.03, P=0.42 and the dominant pooled OR=1.1, P=0.18). The meta-analyses were performed under the fixed-effect model and there was no significant heterogeneity among the effect sizes. CONCLUSION: Meta-analytically combined evidence from the present genotypings and the literature search shows that the effect sizes are homogeneous across studies and that rs4680 is not associated with AN.", "author" : [ { "dropping-particle" : "", "family" : "Brandys", "given" : "Marek K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slof-Op't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elburg", "given" : "Annemarie a", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ophoff", "given" : "Roel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verduijn", "given" : "Willem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Middeldorp", "given" : "Christel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kas", "given" : "Martien J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "Roger a H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatric Genetics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "6" ] ] }, "page" : "130-136", "title" : "Anorexia nervosa and the Val158Met polymorphism of the COMT gene: meta-analysis and new data", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Brandys et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Brandys et al. 2012). To conclude, the evidence supporting the link between dopamine genes and eating disorders is extremely limited, with the strongest, yet still weak evidence, supporting an association with DRD4. Potential reasons for the inconsistencies and lack of findings are small sample sizes and changing diagnostic criteria for eating disorders. Despite the lack of success in genetic association studies, there is significant biological evidence of the role of serotonin in eating disorders. PET (positron emission tomography) studies have revealed that patients recovered from AN have increased binding of DA D2/D3 receptors in the anterior ventral striatum relative to controls, indicating either a reduction in the intrasynaptic dopamine concentrations or an increase in the density or affinity of the D2 and D3 receptors. A decrease in homovanillic acid (HVA), a metabolite of dopamine in the cerebrospinal fluid of recovered AN patients supports a decrease in intrasynamptic dopamine concentrations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.tins.2013.01.003", "ISSN" : "1878-108X", "PMID" : "23333342", "abstract" : "Individuals with anorexia nervosa (AN) engage in relentless restrictive eating and often become severely emaciated. Because there are no proven treatments, AN has high rates of relapse, chronicity, and death. Those with AN tend to have childhood temperament and personality traits, such as anxiety, obsessions, and perfectionism, which may reflect neurobiological risk factors for developing AN. Restricted eating may be a means of reducing negative mood caused by skewed interactions between serotonin aversive or inhibitory and dopamine reward systems. Brain imaging studies suggest that altered eating is a consequence of dysregulated reward and/or awareness of homeostatic needs, perhaps related to enhanced executive ability to inhibit incentive motivational drives. An understanding of the neurobiology of this disorder is likely to be important for developing more effective treatments.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "Walter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierenga", "given" : "Christina E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simmons", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bischoff-Grethe", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Trends in Neurosciences", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "110-120", "publisher" : "Elsevier Ltd", "title" : "Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2013). There is also evidence that patients recovered from AN have feelings of anxiety after the release of dopamine (contrary to the usual euphoria in controls without the disease), indicating that patients with AN may restrict eating to avoid the release of anxiety causing dopamine. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.tins.2013.01.003", "ISSN" : "1878-108X", "PMID" : "23333342", "abstract" : "Individuals with anorexia nervosa (AN) engage in relentless restrictive eating and often become severely emaciated. Because there are no proven treatments, AN has high rates of relapse, chronicity, and death. Those with AN tend to have childhood temperament and personality traits, such as anxiety, obsessions, and perfectionism, which may reflect neurobiological risk factors for developing AN. Restricted eating may be a means of reducing negative mood caused by skewed interactions between serotonin aversive or inhibitory and dopamine reward systems. Brain imaging studies suggest that altered eating is a consequence of dysregulated reward and/or awareness of homeostatic needs, perhaps related to enhanced executive ability to inhibit incentive motivational drives. An understanding of the neurobiology of this disorder is likely to be important for developing more effective treatments.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "Walter H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wierenga", "given" : "Christina E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simmons", "given" : "Alan N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bischoff-Grethe", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Trends in Neurosciences", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "110-120", "publisher" : "Elsevier Ltd", "title" : "Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2013). Specifically in patients with BN, peripheral and central HVA are lower compared to people without the disease and there is evidence that HVA levels which are depressed while suffering from the disease can be returned to normal levels after treatment ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pbb.2010.04.016.Dopamine", "author" : [ { "dropping-particle" : "", "family" : "Bello", "given" : "Nicholas T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hajnal", "given" : "Andras", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pharmacology and Biochemical Behaviours", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "25-33", "title" : "Dopamine and binge eating behaviors", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bello and Hajnal 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bello and Hajnal 2011)2.7.3 NorephinephrineNorepinephrine is thought to influence eating patterns through its actions on the hypothalamic paraventricular nucleus (PVN). Norepinephrine can either increase or reduce eating, depending on where it is and the balance of α1- and α2- adrenoreceptors present. α1- adrenoreceptors supress appetite, while α2- adrenoreceptors increase appetite ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0899-9007", "PMID" : "11054588", "abstract" : "The focus of the present review is to reconsider the role of endogenous norepinephrine (NE) in brain, specifically within the hypothalamic paraventricular nucleus (PVN), with regard to its potential role in eliciting eating or satiety. The PVN is innervated by NE fibers and is a site at which infusion of exogenous NE elicits eating at low doses. Two subtypes of alpha-adrenergic receptors within the PVN exert antagonistic actions on eating in the rat: activation of PVN alpha(2)-adrenoceptors increases eating, whereas activation of PVN alpha(1)-adrenoceptors suppresses eating. Pharmacologic manipulations that elevate NE can increase or decrease food intake, depending on the site and type of NE manipulation. Certain antiobesity drugs may act to reduce eating via release of NE and subsequent activation of alpha(1)-adrenoceptors. The PVN exhibits a reliable rhythm in the secretion of endogenous NE over the dark-and-light cycle, and this rhythm may interact with changes in numbers of PVN alpha(1)- and alpha(2)-adrenoceptors to modulate eating during the dark-and-light cycle. Push-and-pull and microdialysis studies indicate that NE secretion is strongly associated with eating, particularly at the start of the dark phase. The present review considers potential interactions of NE with substances such as leptin and neuropeptide Y that alter eating.", "author" : [ { "dropping-particle" : "", "family" : "Wellman", "given" : "P J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nutrition", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2000", "10" ] ] }, "page" : "837-842", "title" : "Norepinephrine and the control of food intake", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wellman 2000)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wellman 2000). Though there is a plausible role for norepinephrine in eating disorders, very little research has been conducted in the area. One study found a novel 343-bp sequence with 5 additional AAGG repeat islands within the norepinephrine transporter (NET) gene promoter region. In the NET gene promoter polymorphic region (NETpPR), a 4-bp deletion (S4) or insertion (L4) in the AAGG4 resulted in the net loss or gain, respectively, of a putative Elk-1 transcription factor site. There was a significant preferential transmission of L4 (odds ratio 2.1) from parent to child with restricting AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/sj.mp.4001080", "ISSN" : "1359-4184", "PMID" : "12140790", "abstract" : "Long-term weight-restored patients with anorexia nervosa (AN) have lower norepinephrine levels than controls. Since this may reflect altered reuptake by the norepinephrine transporter (NET), we hypothesised that the NET gene was involved in the genetic component of AN. PCR-amplification of an AAGG repeat island (AAGG1) in the NET gene promoter region revealed a novel 343-bp sequence with five additional AAGG repeat islands (AAGG2-AAGG6). We named the sequence from AAGG1 to AAGG6 inclusive, the NET gene promoter polymorphic region (NETpPR). A 4-bp deletion (S4) or insertion (L4) in AAGG4 resulted in the net loss or gain, respectively, of a putative Elk-1 transcription factor site. The transmission disequilibrium test(TDT) with 87 Australian trios (patient plus parents) demonstrated significant preferential transmission of L4 (McNemar's chi(2) = 7.806, df = 1, P = 0.0052, odds ratio: 2.1) from parent to child with restricting AN (AN-R), suggesting that L4 or a DNA variant in linkage disequilibrium with it, doubles the risk for developing AN-R.", "author" : [ { "dropping-particle" : "", "family" : "Urwin", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennetts", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilcken", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lampropoulos", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beumont", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clarke", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Russell", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanner", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nunn", "given" : "K P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular Psychiatry", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2002", "1" ] ] }, "page" : "652-657", "title" : "Anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Urwin et al. 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Urwin et al. 2002). ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/YPG.0b013e3280ae6c2a", "ISSN" : "0955-8829", "PMID" : "17621171", "author" : [ { "dropping-particle" : "", "family" : "Hu", "given" : "Xun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karwautz", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Gudrun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holliday", "given" : "Jo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Tao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collier", "given" : "David a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatric Genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "8" ] ] }, "page" : "247-248", "title" : "No association between a promoter polymorphism in the noradrenaline transporter gene and anorexia nervosa", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Hu et al. (2007)", "previouslyFormattedCitation" : "(Hu et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Hu et al. (2007) attempted to replicate the results, however did not find any statistically significant results in a sample of 142 family trios with AN from London, United Kingdom, and Vienna, Austria. 2.7.4 Neuropeptides and Feed RegulationsOpioids: Opioid receptors are involved in food intake, reward sensitivity, and pain and are thought to play a role in vulnerability to addictive disorders ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev-clinpsy-050212-185546", "ISSN" : "1548-5951", "PMID" : "23537489", "abstract" : "Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.", "author" : [ { "dropping-particle" : "", "family" : "Trace", "given" : "Sara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Jessica H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pe\u00f1as-Lled\u00f3", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Clinical Psychology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "589-620", "title" : "The genetics of eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Trace et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Trace et al. 2013). Endogenous opioids are linked to the enjoyment of food with sweet and fatty foods increasing opioid receptor binding and binge eating leading to changes in the endogenous opioid system, creating a cyclical pattern of binging ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.appet.2009.03.005.The", "author" : [ { "dropping-particle" : "", "family" : "Mathes", "given" : "Wendy Foulds", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brownley, Kimberly", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mo", "given" : "Xiaofei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Appetite", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "545-553", "title" : "The biology of binge eating", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.pbb.2010.04.016.Dopamine", "author" : [ { "dropping-particle" : "", "family" : "Bello", "given" : "Nicholas T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hajnal", "given" : "Andras", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pharmacology and Biochemical Behaviours", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "25-33", "title" : "Dopamine and binge eating behaviors", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mathes et al. 2010; Bello and Hajnal 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mathes et al. 2010; Bello and Hajnal 2011). The current hypothesis is that people with AN have a dysregulation of the opioid system and are predisposed towards being addicted and that restriction and exercise are a means to compensate for the diminished response to reward ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev-clinpsy-050212-185546", "ISSN" : "1548-5951", "PMID" : "23537489", "abstract" : "Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.", "author" : [ { "dropping-particle" : "", "family" : "Trace", "given" : "Sara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Jessica H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pe\u00f1as-Lled\u00f3", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Clinical Psychology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "589-620", "title" : "The genetics of eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Trace et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Trace et al. 2013). Beta-endorphin, an agonist of opioid receptors has been measured in people with eating disorders. In both AN and BN patients it is unclear if beta-endorphin levels, are increased, decreased, or unchanged though overall evidence indicates decreased ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0306-9877", "PMID" : "8748094", "abstract" : "Incidental findings from animal experiments involving administration of exogenous opioid agonists indicate that there are close links between the endogenous opioid system and feeding behaviour. Subsequent investigations aimed at elucidating the nature of the opioid-feeding relationship led to a wide variety of findings, some of them apparently contradictory. This paper examines the effects of opioid agonists and antagonists on feeding behaviour, and considers the evidence relating levels of endogenous opioids to feeding states, with particular reference to certain eating disorders, including anorexia nervosa, bulimia nervosa, Prader-Willi syndrome, and eating-induced obesity. The receptors which may be involved in opioid-feeding relationships are discussed. Relationships between the endogenous opioid system and other systems, such as the dopaminergic, noradrenergic and hormonal systems, are considered insofar as they may have bearing on the modulation of feeding behaviour. Finally, three theories are briefly outlined which attempt to link the endogenous opioid system with feeding modulation and the pathogenesis of certain eating disorders. The suggestion is put forward that anorexia nervosa may represent a pathological consequence of the triggering of a primitive mechanism for coping with unforeseen food shortages which may have short-term advantages, e.g., for masking or temporarily alleviating a depressed state.", "author" : [ { "dropping-particle" : "", "family" : "Johnson", "given" : "R D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Hypotheses", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1995", "11" ] ] }, "page" : "491-497", "title" : "Opioid involvement in feeding behaviour and the pathogenesis of certain eating disorders", "type" : "article-journal", "volume" : "45" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0002-953X", "PMID" : "1353317", "abstract" : "OBJECTIVE: Preclinical and clinical evidence suggests that central opioid dysfunction may play a role in the pathophysiology of the eating disorders. In particular, endogenous opioids are known to regulate feeding behavior, mood, perception, and neuroendocrine function, all of which are disturbed in patients with eating disorders. Although low concentrations of CSF beta-endorphin have been reported in low-weight patients with anorexia nervosa, central opioid activity in normal-weight patients with bulimia nervosa has not been reported. The authors therefore measured CSF concentrations of beta-endorphin and dynorphin in drug-free female patients with DSM-III-R-defined bulimia nervosa and normal comparison subjects. METHOD: After 4 days of a low monoamine diet and overnight bed rest, CSF was obtained (12-26 cc) from 11 women with bulimia and 17 normal comparison subjects (eight women and nine men). RESULTS: The women with bulimia had significantly lower CSF concentrations of beta-endorphin than did the female comparison subjects. However, CSF concentrations of dynorphin were not significantly different in patients and female or male comparison subjects. beta-Endorphin concentrations were inversely correlated with Beck Depression Inventory scores and the depression subscale of the Eating Disorders Inventory. CONCLUSIONS: These data support a role for central opiates in the mediation of the pathophysiology of the signs and symptoms of bulimia nervosa, although it is impossible to rule out the effects of depression on the results.", "author" : [ { "dropping-particle" : "", "family" : "Brewerton", "given" : "T D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lydiard", "given" : "R B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laraia", "given" : "M T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shook", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ballenger", "given" : "J C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "1992", "8" ] ] }, "page" : "1086-1090", "title" : "CSF beta-endorphin and dynorphin in bulimia nervosa", "type" : "article-journal", "volume" : "149" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Brewerton et al. 1992; Johnson 1995)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Brewerton et al. 1992; Johnson 1995). A genome wide linkage analysis of 192 families was conducted finding an association between marker D1S3721 on chromosome 1p with restrictive type AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/339250", "ISSN" : "0002-9297", "PMID" : "11799475", "abstract" : "Eating disorders, such as anorexia nervosa (AN), have a significant genetic component. In the current study, a genomewide linkage analysis of 192 families with at least one affected relative pair with AN and related eating disorders, including bulimia nervosa, was performed, resulting in only modest evidence for linkage, with the highest nonparametric linkage (NPL) score, 1.80, at marker D4S2367 on chromosome 4. Since the reduction of sample heterogeneity would increase power to detect linkage, we performed linkage analysis in a subset (n=37) of families in which at least two affected relatives had diagnoses of restricting AN, a clinically defined subtype of AN characterized by severe limitation of food intake without the presence of binge-eating or purging behavior. When we limited the linkage analysis to this clinically more homogeneous subgroup, the highest multipoint NPL score observed was 3.03, at marker D1S3721 on chromosome 1p. The genotyping of additional markers in this region led to a peak multipoint NPL score of 3.45, thereby providing suggestive evidence for the presence of an AN-susceptibility locus on chromosome 1p.", "author" : [ { "dropping-particle" : "", "family" : "Grice", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halmi", "given" : "K a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fichter", "given" : "M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woodside", "given" : "D B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "J T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplan", "given" : "a S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magistretti", "given" : "P J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berrettini", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Human Genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2002", "3" ] ] }, "page" : "787-792", "title" : "Evidence for a susceptibility gene for anorexia nervosa on chromosome 1", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Grice et al. 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Grice et al. 2002) leading to the investigation of opioid delta receptor (OPRD1), located on chromosome 1 (chr1p36.3-34.3) as a candidate gene. Three of five OPRD1 SNPs were significantly associated with AN (OPRD1(8214T>C), p=0.045 for alleles, OPRD1 (23340A>G), p=0.046 for alleles, OPRD1(47821A>G), p=0.003 for genotypes and 0.01 for alleles) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/sj.mp.4001318", "ISSN" : "1359-4184", "PMID" : "12740597", "abstract" : "Serotonergic and opioidergic neurotransmitter system alterations have been observed in people with eating disorders; the genes for the serotonin 1D receptor (HTR1D) and the opioid delta receptor (OPRD1) are found on chr1p36.3-34.3, a region identified by our group in a linkage analysis of anorexia nervosa (AN). These candidate genes were evaluated for sequence variation and for linkage and association of this sequence variation to AN in family and case : control data sets. Resequencing of the HTR1D locus and a portion of the OPRD1 locus identified novel SNPs and confirmed existing SNPs. Genotype assay development and genotyping of nine SNPs (four at HTR1D and five at OPRD1) was performed on 191 unrelated individuals fulfilling DSM-IV criteria (w/o amenorrhea criterion) for AN, 442 relatives of AN probands and 98 psychiatrically screened controls. Linkage analysis of these candidate gene SNPs with 33 microsatellite markers in families including relative pairs concordantly affected with restricting AN (N=37) substantially increased the evidence for linkage of this region to restricting AN to an NPL score of 3.91. Statistically significant genotypic, allelic, and haplotypic association to AN in the case : control design was observed at HTR1D and OPRD1 with effect sizes for individual SNPs of 2.63 (95% CI=1.21-5.75) for HTR1D and 1.61 (95% CI=1.11-2.44) for OPRD1. Using genotype data on parents and AN probands, three SNPs at HTR1D were found to exhibit significant transmission disequilibrium (P&<0.05). The combined statistical genetic evidence suggests that HTR1D and OPRD1 or linked genes may be involved in the etiology of AN.", "author" : [ { "dropping-particle" : "", "family" : "Bergen", "given" : "a W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bree", "given" : "M B M", "non-dropping-particle" : "van den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yeager", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Welch", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ganjei", "given" : "J K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haque", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bacanu", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berrettini", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grice", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fichter", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halmi", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplan", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woodside", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2003", "4" ] ] }, "page" : "397-406", "title" : "Candidate genes for anorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bergen et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bergen et al. 2003). The association of OPRD1 SNPs with AN was further supported when three gene polymorphisms (rs569356, p=0.0011 for genotype for all types of AN, rs521809, p=0.163 for restrictive subtype, rs4654327, p=0.0246) were found to be associated with AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.biopsych.2006.04.007", "ISSN" : "0006-3223", "PMID" : "16806108", "abstract" : "BACKGROUND: A recent study reported strong evidence for the involvement of a region on human chromosome 1 and genetic susceptibility to anorexia nervosa (AN). A more detailed analysis of this region has suggested 2 genes that may account for this susceptibility. These data suggest that polymorphisms in both the serotonin 1D (HTR1D) and opioid delta 1 (OPRD1) receptor genes show a significant association with restricting AN (RAN). METHODS: In the current study, we have conducted an independent association study on 226 females meeting DSM-IV criteria for AN and 678 matched volunteers. RESULTS: We genotyped 4 SNPs in HTR1D and 6 SNPs in OPRD1. 3 SNPs were found to be associated with both RAN and binge-purge AN (BPAN) within the gene for OPRD1. We also found evidence of association between 2 polymorphisms within HTR1D and RAN. CONCLUSIONS: These data support the hypothesis that polymorphisms within this region form a component of the genetic basis to susceptibility to RAN. However, further work is required to understand the processes that may be mediated by these genes.", "author" : [ { "dropping-particle" : "", "family" : "Brown", "given" : "Kirsty M O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bujac", "given" : "Sarah R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mann", "given" : "Evleen T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "David a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stubbins", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blundell", "given" : "John E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2007", "2", "1" ] ] }, "page" : "367-373", "title" : "Further evidence of association of OPRD1 & HTR1D polymorphisms with susceptibility to anorexia nervosa", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Brown et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Brown et al. 2007). To date, no genetic association studies have been conducted with BN or BED patients. Neuropeptide Y (NPY): Neuropeptide Y is released by both the sympathetic nervous system and from isolated adipocytes and plays a role in adipocyte regulation. Activation of Y2 receptors in abdominal fat prompts the body to store abdominal fat, contributing to obesity as well as increasing appetite ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pharmthera.2014.02.005", "ISSN" : "1879-016X", "PMID" : "24560685", "abstract" : "The evidence describing the autonomic innervation of body fat is reviewed with a particular focus on the role of the sympathetic neurotransmitters. In compiling the evidence, a strong case emerges for the interaction between autonomic nerves and perivascular adipose tissue (PVAT). Adipocytes have been shown to express receptors for neurotransmitters released from nearby sympathetic varicosities such as adrenoceptors (ARs), purinoceptors and receptors for neuropeptide Y (NPY). Noradrenaline can modulate both lipolysis (via \u03b12- and \u03b23-ARs) and lipogenesis (via \u03b11- and \u03b23-ARs). ATP can inhibit lipolysis (via P1 purinoceptors) or stimulate lipolysis (via P2y purinoceptors). NPY, which can be produced by adipocytes and sympathetic nerves, inhibits lipolysis. Thus the sympathetic triad of transmitters can influence adipocyte free fatty acid (FFA) content. Substance P (SP) released from sensory nerves has also been shown to promote lipolysis. Therefore, we propose a mechanism whereby sympathetic neurotransmission can simultaneously activate smooth muscle cells in the tunica media to cause vasoconstriction and alter FFA content and release from adjacent adipocytes in PVAT. The released FFA can influence endothelial function. Adipocytes also release a range of vasoactive substances, both relaxing and contractile factors, including adiponectin and reactive oxygen species. The action of adipokines (such as adiponectin) and reactive oxygen species (ROS) on cells of the vascular adventitia and nerves has yet to be fully elucidated. We hypothesise a strong link between PVAT and autonomic fibres and suggest that this poorly understood relationship is extremely important for normal vascular function and warrants a detailed study.", "author" : [ { "dropping-particle" : "", "family" : "Bulloch", "given" : "Janette M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daly", "given" : "Craig J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pharmacology & Therapeutics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014", "2", "18" ] ] }, "page" : "61-73", "publisher" : "Elsevier Inc.", "title" : "Autonomic nerves and perivascular fat: Interactive mechanisms", "type" : "article-journal", "volume" : "143" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bulloch and Daly 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bulloch and Daly 2014). Activation is thought to occur when body fat stores are diminished and the body is attempting to achieve homeostasis, however in patients with AN, despite increased NPY levels in the spinal fluid and brain, the disease persists ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.yfrne.2008.06.001", "ISSN" : "1095-6808", "PMID" : "18602416", "abstract" : "Outcome in anorexia nervosa remains poor and a new way of looking at this condition is therefore needed. To this aim, we review the effects of food restriction and starvation in humans. It is suggested that body weight remains stable and relatively low when the access to food requires a considerable amount of physical activity. In this condition, the human homeostatic phenotype, body fat content is also low and as a consequence, the synthesis and release of brain neurotransmitters are modified. As an example, the role of neuropeptide Y is analyzed in rat models of this state. It is suggested that the normal behavioral role of neuropeptide Y is to facilitate the search for food and switch attention from sexual stimuli to food. Descriptive neuroendocrine studies on patients with anorexia nervosa have not contributed to the management of the patients and the few studies in which hormones have been administered have, at best, reversed an endocrine consequence secondary to starvation. In a modified framework for understanding the etiology and treatment of anorexia nervosa it is suggested that the condition emerges because neural mechanisms of reward and attention are engaged. The neural neuropeptide Y receptor system may be involved in the maintenance of the behavior of eating disorder patients because the localization of these receptors overlaps with the neural systems engaged in cue-conditioned eating in limbic and cortical areas. The eating behavior of patients with anorexia nervosa, and other eating disorders as well, is viewed as a cause of the psychological changes of the patients. Patients are trained to re-learn normal eating habits using external support and as they do, their symptoms, including the psychological symptoms, dissolve.", "author" : [ { "dropping-particle" : "", "family" : "S\u00f6dersten", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nerg\u00e5rdh", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergh", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zandian", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheurink", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers in Neuroendocrinology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "445-462", "title" : "Behavioral neuroendocrinology and treatment of anorexia nervosa", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(S\u00f6dersten et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(S?dersten et al. 2008). In patients with BN, cerebrospinal fluid (CSF) level concentrations are not significantly different than those without the disease, however, plasma concentrations are significantly elevated ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2013/483145", "ISSN" : "1687-8337", "PMID" : "24106499", "abstract" : "Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.", "author" : [ { "dropping-particle" : "", "family" : "Smitka", "given" : "Kvido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papezova", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vondra", "given" : "Karel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hainer", "given" : "Vojtech", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nedvidkova", "given" : "Jara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "483145", "title" : "The role of \"mixed\" orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: Relevance to food intake and nutritional status in patients with anorexia nervosa", "type" : "article-journal", "volume" : "2013" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Smitka et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Smitka et al. 2013). Only one study to date has tested the genetic association between NPY and eating disorders, finding no association between NPY gene SNP (rs16139) and all eating disorders combined, or AN, BN, and BED separately, p<0.479 for genotype ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/08039488.2010.525258", "ISSN" : "1502-4725", "PMID" : "21047193", "abstract" : "BACKGROUND: Genetic factors likely contribute to the biological vulnerability of eating disorders. AIMS: Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. METHODS: 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. RESULTS: No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. CONCLUSION: Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.", "author" : [ { "dropping-particle" : "", "family" : "Kindler", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zwaan", "given" : "Martina", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fuchs", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leisch", "given" : "Friedrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gr\u00fcn", "given" : "Bettina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strnad", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stojanovic", "given" : "Mirjana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Windisch", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lennkh-Wolfsberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "El-Giamal", "given" : "Nadja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sieghart", "given" : "Werner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasper", "given" : "Siegfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aschauer", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nordic Journal of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "203-207", "title" : "No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kindler et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kindler et al. 2011).Peptide YY (PYY): PYY is secreted by the digestive tract after food consumption, promoting satiety. Two forms of PYY are secreted, PYY1-36 and PYY3-36, with evidence supporting that PYY3-36 may exert its anorectic effect by inhibiting dopamine and norepinephrine release through its bonding on NPY Y2 receptors in the hypothalamus. Negative associations between PYY with leptin and grehlin have also been found. Limited evidence exists about PYY concentrations in those with eating disorders. For those with AN and BN there is conflicting evidence on basal PYY levels, however there may be some effect on PYY after food is consumed ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2013/483145", "ISSN" : "1687-8337", "PMID" : "24106499", "abstract" : "Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.", "author" : [ { "dropping-particle" : "", "family" : "Smitka", "given" : "Kvido", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papezova", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vondra", "given" : "Karel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hainer", "given" : "Vojtech", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nedvidkova", "given" : "Jara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "483145", "title" : "The role of \"mixed\" orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: Relevance to food intake and nutritional status in patients with anorexia nervosa", "type" : "article-journal", "volume" : "2013" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Smitka et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Smitka et al. 2013). Melanocortin Pathway (MC4R): MC4R deficiency is the most common cause of monogenic obesity in addition to contributing to polygenic obesity. MC4R exerts its effect on obesity by regulating appetite through the leptin-melanocortin signalling system ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2012.169", "ISSN" : "1476-5497", "PMID" : "23147118", "abstract" : "Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity and an important contributor to polygenic obesity. MC4R mutations with partial or total loss of function, as well as the variant rs17782313 mapped near MC4R, are positively associated with obesity. MC4R is involved in the leptin-melanocortin signalling system, located in hypothalamic nuclei, that controls food intake via both anorexigenic or orexigenic signals. Impairment in this receptor might affect eating behaviours. Thus, in the case of MC4R mutation carriers, obesity could be related, at least partly, to inadequate control over eating behaviours. Many published studies address eating behaviours in MC4R mutation carriers. Most studies focus on binge eating disorder, whereas others examine various aspects of intake and motivation. Up to now, no evaluation of this literature has been performed. In this review, we examine the available literature on eating behaviours in carriers of MC4R mutations and variant rs17782313 near MC4R gene. We address binge eating disorder, bulimia nervosa, mealtime hyperphagia, snacking, psychological factors, satiety responsiveness and intake of energy and macro/micronutrient. In a small number of studies, MC4R mutations seem to impair eating behaviours or motivation, but no clear causal effects can be found in the balance of the evidence presented. Improvements in methodologies will be necessary to clarify the behavioural effects of MC4R mutations.", "author" : [ { "dropping-particle" : "", "family" : "Valette", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellisle", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carette", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poitou", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubern", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paradis", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muzard", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cl\u00e9ment", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czernichow", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "1027-1035", "title" : "Eating behaviour in obese patients with melanocortin-4 receptor mutations: a literature review", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Valette et al. 2013a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Valette et al. 2013a). Leptin, a hormone released by adipocytes that causes feelings of satiety though the release of anorexigenic peptides, such as POMC, as well as supressing AgRP ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.brainresrev.2009.10.007", "ISSN" : "1872-6321", "PMID" : "19931559", "abstract" : "Anorexia nervosa (AN) is a complex multi-factorial disease with high heritability. The psychological AN symptoms are poorly connected with specific molecular mechanisms. Here we review the molecular basis of AN with the focus on human genetic association studies; we put these in the experimental biological context with emphasis on molecular systems controlling food intake and body weight in a direct or indirect manner. We systematically searched for human genetic studies related to AN and grouped data into main categories/systems reflecting their major known roles: (1) Systems related to mental disorders (serotonin, brain-derived neurotrophic factor (BDNF), norepinephrine (NE), glutamate (NMDA) receptor and SK3 channel, KCCN3). (2) Hunger regulatory systems (leptin, AGRP, MSH, melanocortin 4 receptor (MC4R), NPY, ghrelin, cholecystokinin (CCK). (3) Feeding motivation- and reward-related systems (opioids, OPRD1, cannabinoids (anandamide (AEA), THC, CBR1), dopamine, DRD2, DRD3, DRD4, catecholamine-O-methyl transferase (COMT). (4) Systems regulating energy metabolism (uncoupling proteins 2 and 3 (UCP2 and UCP3). (5) Neuroendocrine systems with emphasis on sex hormones (estrogen receptor-beta (ESR2). (6) The immune system and inflammatory response (tumor necrosis factor-alpha (TNF-alpha)). Overall, we found that in total 175 association studies have been performed on AN cohorts on 128 different polymorphisms related to 43 genes. We review the strongest associations, identify some genes that have an important role in regulating BMI whose possible relationship to AN has not been investigated and discuss the potential targets for pharmacological interventions.", "author" : [ { "dropping-particle" : "", "family" : "Rask-Andersen", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olszewski", "given" : "Pawel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Allen S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f6th", "given" : "Helgi B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain Research Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "147-164", "publisher" : "Elsevier B.V.", "title" : "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ijo.2012.169", "ISSN" : "1476-5497", "PMID" : "23147118", "abstract" : "Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity and an important contributor to polygenic obesity. MC4R mutations with partial or total loss of function, as well as the variant rs17782313 mapped near MC4R, are positively associated with obesity. MC4R is involved in the leptin-melanocortin signalling system, located in hypothalamic nuclei, that controls food intake via both anorexigenic or orexigenic signals. Impairment in this receptor might affect eating behaviours. Thus, in the case of MC4R mutation carriers, obesity could be related, at least partly, to inadequate control over eating behaviours. Many published studies address eating behaviours in MC4R mutation carriers. Most studies focus on binge eating disorder, whereas others examine various aspects of intake and motivation. Up to now, no evaluation of this literature has been performed. In this review, we examine the available literature on eating behaviours in carriers of MC4R mutations and variant rs17782313 near MC4R gene. We address binge eating disorder, bulimia nervosa, mealtime hyperphagia, snacking, psychological factors, satiety responsiveness and intake of energy and macro/micronutrient. In a small number of studies, MC4R mutations seem to impair eating behaviours or motivation, but no clear causal effects can be found in the balance of the evidence presented. Improvements in methodologies will be necessary to clarify the behavioural effects of MC4R mutations.", "author" : [ { "dropping-particle" : "", "family" : "Valette", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellisle", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carette", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poitou", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubern", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paradis", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muzard", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cl\u00e9ment", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czernichow", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "1027-1035", "title" : "Eating behaviour in obese patients with melanocortin-4 receptor mutations: a literature review", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rask-Andersen et al. 2010; Valette et al. 2013a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rask-Andersen et al. 2010; Valette et al. 2013a). When POMC is cleaved, it produces α-MSH which then binds to MC4R to decrease food intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2012.169", "ISSN" : "1476-5497", "PMID" : "23147118", "abstract" : "Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity and an important contributor to polygenic obesity. MC4R mutations with partial or total loss of function, as well as the variant rs17782313 mapped near MC4R, are positively associated with obesity. MC4R is involved in the leptin-melanocortin signalling system, located in hypothalamic nuclei, that controls food intake via both anorexigenic or orexigenic signals. Impairment in this receptor might affect eating behaviours. Thus, in the case of MC4R mutation carriers, obesity could be related, at least partly, to inadequate control over eating behaviours. Many published studies address eating behaviours in MC4R mutation carriers. Most studies focus on binge eating disorder, whereas others examine various aspects of intake and motivation. Up to now, no evaluation of this literature has been performed. In this review, we examine the available literature on eating behaviours in carriers of MC4R mutations and variant rs17782313 near MC4R gene. We address binge eating disorder, bulimia nervosa, mealtime hyperphagia, snacking, psychological factors, satiety responsiveness and intake of energy and macro/micronutrient. In a small number of studies, MC4R mutations seem to impair eating behaviours or motivation, but no clear causal effects can be found in the balance of the evidence presented. Improvements in methodologies will be necessary to clarify the behavioural effects of MC4R mutations.", "author" : [ { "dropping-particle" : "", "family" : "Valette", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellisle", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carette", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poitou", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubern", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paradis", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muzard", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cl\u00e9ment", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czernichow", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "1027-1035", "title" : "Eating behaviour in obese patients with melanocortin-4 receptor mutations: a literature review", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Valette et al. 2013a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Valette et al. 2013a). The agouti protein, closely related to AgRP, which has been extensively studied in mice because of its link to obesity, hyperphagia, hyperinsulimia, hyperglycemia (in males), and ability to antagonize MC4R preventing α-MSH from binding ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Corander", "given" : "Marcus P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coll", "given" : "Anthony P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Pharmacology", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "111-118", "title" : "Melanocortins and body weight regulation: Glucocorticoids, agouti-related protein and beyond", "type" : "article-journal", "volume" : "1" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Corander and Coll 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Corander and Coll 2011). When AGRB binds to MC4R it promotes food consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2012.169", "ISSN" : "1476-5497", "PMID" : "23147118", "abstract" : "Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity and an important contributor to polygenic obesity. MC4R mutations with partial or total loss of function, as well as the variant rs17782313 mapped near MC4R, are positively associated with obesity. MC4R is involved in the leptin-melanocortin signalling system, located in hypothalamic nuclei, that controls food intake via both anorexigenic or orexigenic signals. Impairment in this receptor might affect eating behaviours. Thus, in the case of MC4R mutation carriers, obesity could be related, at least partly, to inadequate control over eating behaviours. Many published studies address eating behaviours in MC4R mutation carriers. Most studies focus on binge eating disorder, whereas others examine various aspects of intake and motivation. Up to now, no evaluation of this literature has been performed. In this review, we examine the available literature on eating behaviours in carriers of MC4R mutations and variant rs17782313 near MC4R gene. We address binge eating disorder, bulimia nervosa, mealtime hyperphagia, snacking, psychological factors, satiety responsiveness and intake of energy and macro/micronutrient. In a small number of studies, MC4R mutations seem to impair eating behaviours or motivation, but no clear causal effects can be found in the balance of the evidence presented. Improvements in methodologies will be necessary to clarify the behavioural effects of MC4R mutations.", "author" : [ { "dropping-particle" : "", "family" : "Valette", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellisle", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carette", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poitou", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubern", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paradis", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Muzard", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cl\u00e9ment", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czernichow", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "1027-1035", "title" : "Eating behaviour in obese patients with melanocortin-4 receptor mutations: a literature review", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Valette et al. 2013a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Valette et al. 2013a).Leptin: Leptin levels are negatively associated with obesity and people suffering from AN have significantly reduced leptin levels compared to controls, as well as increased soluble leptin receptor levels ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1365-2265.2007.02944.x", "ISSN" : "0300-0664", "PMID" : "17953628", "abstract" : "OBJECTIVE: To study the influence of chronic malnutrition in patients with anorexia nervosa on endocrine function of adipose tissue on both circulating and subcutaneous fat mRNA expression level. PATIENTS AND DESIGN: A total of 12 patients with anorexia nervosa and 18 normal weight age-matched women underwent anthropometric examination, single blood drawing and subcutaneous adipose tissue biopsy. MEASUREMENTS: Serum concentrations of high-sensitive CRP (hsCRP), leptin, soluble leptin receptor, adiponectin, resistin, interleukin-6 and insulin were measured by Luminex, enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) kits. Subcutaneous adipose tissue mRNA expression of the same adipokines, adiponectin receptors 1 and 2 and immunocompetent cells marker CD68 was measured by real-time polymerase chain reaction (PCR). RESULTS: Decreased body fat content of patients with anorexia nervosa was accompanied by reduced hsCRP, leptin and increased adiponectin and soluble leptin receptor. Resistin, interleukin-6 and insulin levels did not differ from those of the control group. Fat mRNA adiponectin, leptin, interleukin-6 and CD68 expression was reduced, resistin mRNA expression was increased and adiponectin receptor 1 and 2 expression were unchanged as compared to the control group. CONCLUSIONS: Local perturbations in resistin, adiponectin and interleukin-6 mRNA expression in subcutaneous adipose tissue are not reflected by its circulating levels. These changes could be involved in some local metabolic disturbances in subcutaneous adipose tissue of anorexia nervosa patients.", "author" : [ { "dropping-particle" : "", "family" : "Dolezalova", "given" : "Radka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacinova", "given" : "Zdena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dolinkova", "given" : "Marketa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kleiblova", "given" : "Petra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haluzikova", "given" : "Denisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Housa", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papezova", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haluzik", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Endocrinology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2007", "11" ] ] }, "page" : "674-678", "title" : "Changes of endocrine function of adipose tissue in anorexia nervosa: comparison of circulating levels versus subcutaneous mRNA expression", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0306-4530", "PMID" : "10938446", "abstract" : "Leptin is a protein produced by the ob-ob gene which inhibits food intake. Plasma levels have previously been reported to be altered in obesity and anorexia nervosa (AN) but not bulimia nervosa (BN). We measured fasting plasma leptin levels by radioimmunoassay in 53 subjects carefully studied at NIMH, including 37 women meeting DSM-III-R criteria for BN [10 with concurrent AN (body mass index (BMI)=14.1+/-1.4), 27 without AN (BMI=20.4+/-1.6)] and 16 normal control women (NCs) (BMI=21.1+/-2.0). Patients were medication-free and abstinent from bingeing and purging for three to four weeks prior to study. Plasma leptin levels were significantly correlated to BMI (r=0.41, P<0.002), weight (kg, r=0.43, P<0.001), and percent average body weight (%ABW, r=0.45, P<0.001) in the total group. Plasma leptin levels were lower in the BN subjects (3.4+/-2.5 ng/ml) compared to the NCs (6.1+/-2.6 ng/ml, P<0.001, ANCOVA) even after controlling for BMI and weight. There was no significant difference between BN subjects with AN (n=10, 2.6+/-2.6 ng/ml) and those without AN (n=27, 3.8+/-2.4 ng/ml), despite lower BMI in BN with AN. Furthermore, leptin levels were decreased in BN without AN compared with healthy controls, even though BMI was comparable in these two subgroups. Plasma leptin concentrations were negatively correlated with baseline plasma cortisol levels (n=49, r=-0.49, P<0.001) and positively correlated with prolactin responses following L-tryptophan (n=49, r=0.37, P<0.009) and m-chlorophenylpiperazine (n=52, r=0.24, P<0.09). This is the first known report of decreased plasma leptin levels in BN. The decrement in leptin concentration is not related to BMI, body weight, or the presence or absence of BN. HPA axis activation as well as serotonin dysregulation may be related to decreased leptin levels, which may in turn contribute to disinhibited eating in BN. Although current leptin levels were not correlated with self-reported previous binge frequency, the role of leptin in the pathophysiology of BN deserves further study.", "author" : [ { "dropping-particle" : "", "family" : "Brewerton", "given" : "T D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lesem", "given" : "M D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kennedy", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garvey", "given" : "W T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychoneuroendocrinology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2000", "10" ] ] }, "page" : "649-658", "title" : "Reduced plasma leptin concentrations in bulimia nervosa", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Brewerton et al. 2000; Dolezalova et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Brewerton et al. 2000; Dolezalova et al. 2007). The evidence is less clear with BN patients who may experience a decrease, increase, or no change in leptin levels. It appears that severity and duration of the disease may play a role in decreasing leptin levels. In BED, no changes in leptin have been observed ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Monteleone", "given" : "Palmiero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "DiLieto", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaldo", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maj", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "CNS Spectrums", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "523-529", "title" : "Leptin functioning in eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Monteleone et al. 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Monteleone et al. 2004). The leptin receptor was of interest because it is located in 1p31.2, close to the marker at 1p34.2 previously identified for increasing susceptibility to AN through linkage studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/339250", "ISSN" : "0002-9297", "PMID" : "11799475", "abstract" : "Eating disorders, such as anorexia nervosa (AN), have a significant genetic component. In the current study, a genomewide linkage analysis of 192 families with at least one affected relative pair with AN and related eating disorders, including bulimia nervosa, was performed, resulting in only modest evidence for linkage, with the highest nonparametric linkage (NPL) score, 1.80, at marker D4S2367 on chromosome 4. Since the reduction of sample heterogeneity would increase power to detect linkage, we performed linkage analysis in a subset (n=37) of families in which at least two affected relatives had diagnoses of restricting AN, a clinically defined subtype of AN characterized by severe limitation of food intake without the presence of binge-eating or purging behavior. When we limited the linkage analysis to this clinically more homogeneous subgroup, the highest multipoint NPL score observed was 3.03, at marker D1S3721 on chromosome 1p. The genotyping of additional markers in this region led to a peak multipoint NPL score of 3.45, thereby providing suggestive evidence for the presence of an AN-susceptibility locus on chromosome 1p.", "author" : [ { "dropping-particle" : "", "family" : "Grice", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halmi", "given" : "K a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fichter", "given" : "M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woodside", "given" : "D B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "J T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaplan", "given" : "a S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Magistretti", "given" : "P J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldman", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berrettini", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Human Genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2002", "3" ] ] }, "page" : "787-792", "title" : "Evidence for a susceptibility gene for anorexia nervosa on chromosome 1", "type" : "article-journal", "volume" : "70" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Grice et al. 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Grice et al. 2002). Despite mutations causing a complete lack of circulating leptin irrevocably leading to severe obesity without exogenous leptin treatment ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Bastard", "given" : "Jean-Phillipe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feve", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biochimie", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "2063-2190", "title" : "The secretory face of the adipose cell: A trbiute to two queens, leptin and adiponectin", "type" : "article-journal", "volume" : "94" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bastard and Feve 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bastard and Feve 2012), there is no evidence that genetic variants in LEP or LEPR are associated with any eating disorders. Three LEPR SNPs (Lys109Arg, Gln223Arg, Lys656Asn) were compared in females with and without AN, however there were no significant differences in allele or genotype frequency, even when AN patients were categorized into restrictive and purging types ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0955-8829", "PMID" : "15564891", "abstract" : "Anorexia nervosa is an eating disorder of unknown aetiology. There is significant evidence for a genetic component in the pathogenesis of this disorder. A region on chromosome 1 has been identified as a susceptibility locus. The leptin receptor has been mapped to a similar region, further upstream of this susceptibility locus. Leptin and its receptor are known to be important factors in the control and regulation of body weight. Single nucleotide polymorphisms (SNPs) in the leptin receptor are associated with measures of body weight. In the present study, SNPs in the coding region of the leptin receptor were analysed and their possible association with anorexia nervosa was investigated. Two cohorts of young women, 176 Caucasian anorexia nervosa patients and 152 normal Caucasian females, were genotyped for three SNPs in the leptin receptor. There was no significant difference in allele or genotype frequency, for any SNP, between the normal controls and the cohort of anorexia subjects. There were no significant associations with any genotype and body mass index in either the control or anorexic cohorts. When the anorexic cohort was subdivided into restricting and bingeing/purging behaviours, we found no significant association with any genotype. Analysis of haplotypes showed no significant evidence of association with anorexia. In summary, leptin receptor SNPs do not appear to be important factors in the regulation of body weight in young, pre-menopausal women or have any significant association with anorexia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Quinton", "given" : "N D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meechan", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eastwood", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blakemore", "given" : "a I F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatric Genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2004", "12" ] ] }, "page" : "191-194", "title" : "Single nucleotide polymorphisms in the leptin receptor gene: studies in anorexia nervosa", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Quinton et al. 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Quinton et al. 2004). Similarly, two novel mutations in the coding region of the leptin gene (ser-91-ser; glu-126-gln), and a novel polymorphism (-1387 G/A) in the leptin gene linked upstream region (LEGLUR) were not found to be associated with AN, BN, underweight, or early onset obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1359-4184", "PMID" : "9857981", "abstract" : "Mutations in the leptin gene can result in profound obesity in both rodents and humans. In humans, serum leptin levels correlate with body mass index (BMI: kg m(-2)). However, in patients with anorexia nervosa (AN) leptin levels are lower than in BMI-matched healthy controls. We had previously argued that genes involved in weight regulation should be considered as candidate genes for AN. To investigate this hypothesis we screened the coding region of the leptin gene and part of the leptin gene linked upstream region (LEGLUR) in 49 patients with AN and 315 children and adolescents with extreme obesity. Two novel mutations in the coding region (Ser-91-Ser; Glu-126-Gln), each found in a single proband, and a novel polymorphism in the LEGLUR (position -1387 G/A; frequency of both alleles approximately 0.50) were identified. Tests for association of LEGLUR polymorphism alleles were negative by comparing allele frequencies between 115 AN patients, 71 bulimia nervosa patients, 315 extremely obese children and adolescents, 141 healthy underweights and 50 controls that were not selected for body weight. Tests for transmission disequilibrium were also negative. Hence, an influence of variations in the leptin gene on eating disorders or extreme early onset obesity could not be detected.", "author" : [ { "dropping-particle" : "", "family" : "Hinney", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bornscheuer", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Depenbusch", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mierke", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "T\u00f6lle", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Middeke", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ziegler", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roth", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zamzow", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ballauff", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamann", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mayer", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siegfried", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehmkuhl", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poustka", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "M H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hermann", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpertz-Dahlmann", "given" : "B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fichter", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Remschmidt", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular Psychiatry", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1998", "11" ] ] }, "page" : "539-543", "title" : "No evidence for involvement of the leptin gene in anorexia nervosa, bulimia nervosa, underweight or early onset extreme obesity: identification of two novel mutations in the coding sequence and a novel polymorphism in the leptin gene linked upstream regio", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hinney et al. 1998)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hinney et al. 1998)Proopiomelancortin Gene (POMC): There are not any studies to date investigating genetic variants in POMC and eating disorders. Agouti Related Peptide (AgRP): In patients with AN, AgRP is elevated, however after returning to a normal weight, AgRP are similar to healthy controls ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S0033291711000365", "ISSN" : "1469-8978", "PMID" : "21426605", "abstract" : "BACKGROUND: An imbalance in appetite-regulating neuropeptides of the central nervous system has been associated with anorexia nervosa (AN), but the mechanisms of action are poorly understood. Agouti-related protein (AGRP), an orexigenic mediator of the hypothalamus, increases food intake and decreases energy expenditure in times of negative energy balance. The aim of the present study was to investigate AGRP in acute and fully weight-restored patients with AN, as well as during weight gain. METHOD: Plasma AGRP and leptin levels were assessed using an enzyme-linked immunosorbent assay kit in a total of 175 female participants, including 75 patients with acute AN, 37 weight-restored AN patients and 63 healthy controls. Of the patients with acute AN, 33 were reassessed after partial weight gain. RESULTS: In weight-restored AN patients plasma AGRP levels were similar to those in healthy controls, whereas in patients with acute AN, AGRP was elevated. AGRP was inversely correlated with indicators of undernutrition such as body mass index and plasma leptin. In addition, AGRP levels normalized during weight gain of longitudinally assessed AN patients. CONCLUSIONS: Our results underline the significance of undernutrition and hypoleptinemia for the interpretation of peripheral AGRP concentrations. This provides support for the hypothesis that abnormal AGRP plasma levels in AN patients reflect undernutrition, rather than disease-specific traits.", "author" : [ { "dropping-particle" : "V", "family" : "Merle", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haas", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burghardt", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00f6hler", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schneider", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehmkuhl", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehrlich", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Medicine", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2011", "10" ] ] }, "page" : "2183-2192", "title" : "Agouti-related protein in patients with acute and weight-restored anorexia nervosa", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.psyneuen.2006.06.006", "ISSN" : "0306-4530", "PMID" : "16904835", "abstract" : "Agouti-related protein (AGRP) is the competitive antagonist of alpha-melanocyte stimulating hormone (alpha-MSH) located at melanocortin receptors 3 and 4 (MC3R and MC4R), and also acts as an MC4R inverse agonist. Hypothalamic AGRP controls food intake and body weight in rodents. It has also been found in human plasma. To study the possibility of disturbances in melanocortin receptor-related peptides in eating disorders, plasma AGRP, alpha-MSH, and leptin levels were measured in 18 female patients with anorexia nervosa (AN) (age, 23.5+/-7.1 yr; body mass index (BMI) 14.5+/-1.8 kg/m(2)) and 17 age-matched female controls (age, 25.8+/-3.9 yr; BMI 20.2+/-1.6 kg/m(2)). Blood samples were collected after overnight fasting, and plasma peptides levels were measured using ELISA. Plasma AGRP levels increased significantly in AN patients when compared with controls (P<0.01) while plasma alpha-MSH levels were not significantly different. Plasma leptin levels decreased significantly in AN patients when compared with controls (P<0.001). In addition, plasma AGRP levels were negatively correlated with leptin (r=-0.41, P<0.01) and BMI (r=-0.40, P<0.05) in all subjects. In conclusion, plasma AGRP elevation may be related to energy homeostasis disturbance in AN, and in addition to leptin, peripheral AGRP levels could be used as a nutritional marker in AN patients.", "author" : [ { "dropping-particle" : "", "family" : "Moriya", "given" : "Junko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takimoto", "given" : "Yoshiyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoshiuchi", "given" : "Kazuhiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimosawa", "given" : "Tatsuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akabayashi", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychoneuroendocrinology", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2006", "10" ] ] }, "page" : "1057-1061", "title" : "Plasma agouti-related protein levels in women with anorexia nervosa", "type" : "article-journal", "volume" : "31" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Moriya et al. 2006; Merle et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Moriya et al. 2006; Merle et al. 2011). In BN, there is a negative correlation between AgRP and self-reported BN symptoms ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.eatbeh.2010.09.008", "ISSN" : "1873-7358", "PMID" : "21184980", "abstract" : "The aim of this study was to verify the relationship between eating disorders (binge eating and bulimia nervosa) and body image dissatisfaction with BMI, anorexigenic and orexigenic factors in adolescents. Thirty-two adolescents, (13 obese [BMI=36.65\u00b15.68] and 19 non-obese [BMI=22.18\u00b13.11]), aged between 14 and 19y, were recruited. Symptoms of eating disorders were measured by self-report questionnaires (BSQ, BITE and BES). Hormones, cytokines and neuropeptides were determined by Elisa kits (Phoenix peptide). A positive correlation was found between: leptin and BES (r=.724), BSQ (r=.705) and BITE (r=.696); BMI and BES (r=.663), BSQ (r=.525) and BITE (r=.732); the same pattern was observed to insulin and TNF-\u03b1. A negative correlation was found in \u03b1-MSH and AgRP with BES, BSQ and BITE. Blood levels of hormones and neuropeptides could be the link between obesity and eating disorders in adolescents. However, it is not clear which is the cause and which is the consequence.", "author" : [ { "dropping-particle" : "", "family" : "Lofrano-Prado", "given" : "Mara Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Do", "family" : "Prado", "given" : "Wagner Luiz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Piano", "given" : "Aline", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tock", "given" : "Lian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caranti", "given" : "Danielle Arisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Do", "family" : "Nascimento", "given" : "Claudia Maria Oller", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oyama", "given" : "Lila Missae", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tufik", "given" : "Sergio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mello", "given" : "Marco T\u00falio", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00e2maso", "given" : "Ana Raimunda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eating Behaviors", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "78-82", "title" : "Eating disorders in adolescents: correlations between symptoms and central control of eating behavior", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Lofrano-Prado et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Lofrano-Prado et al. 2011). Only two studies have investigated the genetic relationship between AgRP SNPs and eating disorders. A significant effect of Ala67Thr-AGRP (p=0.046) and AN was found ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.psyneuen.2006.11.003", "ISSN" : "0306-4530", "PMID" : "17197106", "abstract" : "Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.", "author" : [ { "dropping-particle" : "", "family" : "Dardennes", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zizzari", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tolle", "given" : "Virginie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foulon", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kipman", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romo", "given" : "Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iancu-Gontard", "given" : "Dana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boni", "given" : "Claudette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinet", "given" : "Pierre-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Th\u00e9r\u00e8se Bluet", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estour", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mouren", "given" : "Marie-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guelfi", "given" : "Julien-Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rouillon", "given" : "Fr\u00e9d\u00e9ric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorwood", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Epelbaum", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychoneuroendocrinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "2" ] ] }, "page" : "106-113", "title" : "Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and age of onset", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dardennes et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dardennes et al. 2007) as well as a relationship between two mutations in perfect linkage disequilibrium, 760A and 526A in AgRP and AN with carriers 2.63 times more likely to develop AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/sj.mp.4000854", "ISSN" : "1359-4184", "PMID" : "11326303", "abstract" : "Anorexia nervosa (AN) is a life threatening disorder affecting mostly adolescent women. It is a dramatic psychiatric syndrome accompanied by severe weight loss, hyperactivity and neuroendocrine changes (reviewed in Refs 1 and 2). Several studies have shown a strong genetic component in AN (reviewed in Ref 3). Recent advances in unraveling the mechanisms of weight control point to a crucial role of the melanocortin-4 receptor (MC4-r) system in regulating body weight. The orexigenic neuropeptide agouti-related protein (AGRP), a MC4-r antagonist, plays a crucial role in maintaining body weight, by inducing food intake. The sequence of the coding region of the human AGRP gene (AGRP) was determined and the AGRP of 100 patients with AN was screened for variations. Three single nucleotide polymorphisms (SNPs) were identified and screened in a further 45 patients and 244 controls. Two alleles were in complete linkage disequilibrium and were significantly enriched in anorectic patients (11%; P = 0.015) compared to controls (4.5%). These data indicate that variations of AGRP are associated with susceptibility for AN. This is possibly caused by defective suppression of the MC4-r by the variant AGRP, leading to a decreased feeding signal, increasing the risk of developing AN. These results implicate that antagonism of the MC4-r might be considered as pharmacotherapy for patients with AN.", "author" : [ { "dropping-particle" : "", "family" : "Vink", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elburg", "given" : "A A", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goozen", "given" : "S H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandkuijl", "given" : "L A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinke", "given" : "R J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpertz-Dahlmann", "given" : "B M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Remschmidt", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Engeland", "given" : "H", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "R A H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2001", "5" ] ] }, "page" : "325-328", "title" : "Association between an agouti-related protein gene polymorphism and anorexia nervosa", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Vink et al. 2001)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Vink et al. 2001).Melanocortin 4 Receptor (MC4R): Four studies have investigated the association of functional MC4R mutations and BED in obese people. No studies have been conducted for BN or AN. Three of the four studies found no association ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2013.190", "ISSN" : "1476-5497", "PMID" : "24105491", "abstract" : "Melanocortin-4 receptor (MC4R) gene mutations are involved in the leptin-melanocortin pathways that control food intake. The effect of these mutations on eating behavior phenotypes is still debated. To determine the association between functional MC4R mutations and eating behaviors, dietary intake and physical activity, we sequenced the MC4R gene in 4653 obese adults. Among them, 19 adults carriers of functional MC4R mutation were matched on age, sex and body mass index with two randomly-paired controls without MC4R mutation (n=57). We found that eating behaviors and physical activity did not differ between groups. In particular, cases were not at increased risk of binge eating disorders. Subjects carriers of MC4R mutation reported a higher proportion of dietary carbohydrates intakes (43.2\u00b17.1 and 39.2\u00b18.1% of total energy intake, respectively, P=0.048) and a lower proportion of dietary lipids (34.3\u00b16.7 and 38.5\u00b16.7% of total energy intake, respectively, P=0.018). In conclusion, mutation carriers differ from controls by a higher consumption of carbohydrates counterbalanced by a lower consumption of lipids expressed as percentage of total energy intake. However, functional MC4R mutations do not have a higher risk of compulsive eating contrary to what was previously suggested.International Journal of Obesity advance online publication, 5 November 2013; doi:10.1038/ijo.2013.190.", "author" : [ { "dropping-particle" : "", "family" : "Valette", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Poitou", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesse-Guyot", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellisle", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carette", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beyec", "given" : "J", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cl\u00e9ment", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czernichow", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "10", "9" ] ] }, "page" : "883-885", "title" : "Association between melanocortin-4 receptor mutations and eating behaviors in obese patients: a case-control study", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1210/jc.2005-1411", "ISSN" : "0021-972X", "PMID" : "16507637", "abstract" : "CONTEXT: Heterozygous mutations in the melanocortin-4 receptor (MC4R) gene are the most common monogenic form of severe obesity in children. There are conflicting reports regarding the prevalence, nature, and pathogenic effects of MC4R mutations in adults with severe late-onset obesity. OBJECTIVE: Our objective was to determine the prevalence of MC4R mutations in a cohort of severely obese adults and to determine the clinical phenotype and the phenotype-genotype relationship within adult MC4R mutation carriers. DESIGN AND SETTING: We conducted an observational study at a referral center. PATIENTS OR OTHER PARTICIPANTS: Participants included 769 adult patients with body mass index of at least 35 kg/m(2) and 444 nonobese control individuals. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: We assessed the prevalence of pathogenic MC4R mutations, functional characteristics of the detected mutations, phenotype, and phenotype-genotype relationship within mutation carriers. RESULTS: The global prevalence of obesity-specific MC4R mutations was 2.6%, and the 95% confidence interval (CI(95)) was 1.5-3.7. The prevalence of MC4R mutations was similar in patients developing obesity in childhood (2.83%; CI(95), 0.9-4.8) and in patients with a later onset of the disease (2.35%; CI(95), 0.9-3.8). Adult obese MC4R mutation carriers did not present with binge eating or with any specific clinical phenotype. The severity of the functional alterations of the mutated MC4Rs and in particular the intracellular retention of the receptor correlates both with the severity and the onset of the obesity in the mutation carriers. CONCLUSIONS: Obese adult carriers of functionally relevant MC4R mutations do not specifically present with binge-eating disorder or a history of early-onset obesity. The onset and severity of the obesity in the carriers is related to the functional severity of the MC4R mutations.", "author" : [ { "dropping-particle" : "", "family" : "Lubrano-Berthelier", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dubern", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacorte", "given" : "Jean-Marc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Picard", "given" : "Franck", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shapiro", "given" : "Astrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Sumei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bertrais", "given" : "Sandrine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Basdevant", "given" : "Arnaud", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clement", "given" : "Karine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaisse", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "1811-1818", "title" : "Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating", "type" : "article-journal", "volume" : "91" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/sj.mp.4001491", "ISSN" : "1359-4184", "PMID" : "15037865", "abstract" : "Recently, Branson and coworkers reported a strong association between binge-eating disorder (BED) and variants in the melanocortin-4 receptor gene (MC4R). In the current study, we compared the eating behavior of 43 obese probands with functionally relevant MC4R mutations and of 35 polymorphism carriers (V103I or I251L) with wild-type carriers. The module for eating disorders of the Composite International Diagnostic Interview was used to identify binge-eating behavior. The Three-Factor Eating Questionnaire and the Leeds Food Frequency Questionnaire were used to assess restrained eating, disinhibition, hunger and percent total energy intake as fat. No significant differences between carriers of MC4R variants and wild-type carriers were detected. In particular, we found no evidence for an increased rate of binge-eating behavior in obese carriers of MC4R variants. Our findings do not support the strong association between BED and MC4R carrier status.", "author" : [ { "dropping-particle" : "", "family" : "Hebebrand", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geller", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dempfle", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heinzel-Gutenbrunner", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raab", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerber", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wermter", "given" : "A-K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horro", "given" : "F F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blundell", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sch\u00e4fer", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Remschmidt", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpertz", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular Psychiatry", "id" : "ITEM-3", "issue" : "8", "issued" : { "date-parts" : [ [ "2004", "8" ] ] }, "page" : "796-800", "title" : "Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hebebrand et al. 2004; Lubrano-Berthelier et al. 2006; Valette et al. 2013b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hebebrand et al. 2004; Lubrano-Berthelier et al. 2006; Valette et al. 2013b) while one study found that all obese people with MC4R functional mutations display binge eating behaviour compared to 14.2% of obese people without mutations and 0% of normal weight subjects without mutations (p<0.001) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1056/NEJMoa021971", "ISSN" : "1533-4406", "PMID" : "12646666", "abstract" : "BACKGROUND: Obesity, a multifactorial disease caused by the interaction of genetic factors with the environment, is largely polygenic. A few mutations in these genes, such as in the leptin receptor (LEPR) gene and melanocortin 4 receptor (MC4R) gene, have been identified as causes of monogenic obesity. METHODS: We sequenced the complete MC4R coding region, the region of the proopiomelanocortin gene (POMC) encoding the alpha melanocyte-stimulating hormone, and the leptin-binding domain of LEPR in 469 severely obese white subjects (370 women and 99 men; mean [+/-SE] age, 41.0+/-0.5 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 44.1+/-2.0). Fifteen women and 10 men without a history of dieting or a family history of obesity served as normal-weight controls (age, 47.7+/-2.0 years; body-mass index, 21.6+/-0.4). Detailed phenotypic data, including information on body fat, resting energy expenditure, diet-induced thermogenesis, serum concentrations of leptin, and eating behavior, were collected. RESULTS: Twenty-four obese subjects (5.1 percent) and one control subject (4 percent) had MC4R mutations, including five novel variants. Twenty of the 24 obese subjects with an MC4R mutation were matched for age, sex, and body-mass index with 120 of the 445 obese subjects without an MC4R mutation. All mutation carriers reported binge eating, as compared with 14.2 percent of obese subjects without mutations (P<0.001) and 0 percent of the normal-weight subjects without mutations. The prevalence of binge eating was similar among carriers of mutations in the leptin-binding domain of LEPR and noncarriers. No mutations were found in the region of POMC encoding alpha melanocyte-stimulating hormone. CONCLUSIONS: Binge eating is a major phenotypic characteristic of subjects with a mutation in MC4R, a candidate gene for the control of eating behavior.", "author" : [ { "dropping-particle" : "", "family" : "Branson", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potoczna", "given" : "Natascha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kral", "given" : "John G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lentes", "given" : "Klaus-Ulrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoehe", "given" : "Margret R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England Journal of Medicine", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2003", "3", "20" ] ] }, "page" : "1096-1103", "title" : "Binge eating as a major phenotype of melanocortin 4 receptor gene mutations", "type" : "article-journal", "volume" : "348" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Branson et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Branson et al. 2003). However, this study used a different questionnaire to diagnose BED and was done in a sample eligible for bariatric surgery that may not generalizable to other obese populations. Ghrelin: Ghrelin is an appetite-stimulating hormone that increases during fasting and decreases following a meal and that is inversely associated with BMI ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pnpbp.2012.08.011", "ISSN" : "1878-4216", "PMID" : "22960103", "abstract" : "There is growing evidence supporting a multifactorial etiology that includes genetic, neurochemical, and physiological components for eating disorders above and beyond the more conventional theories based on psychological and sociocultural factors. Ghrelin is one of the key gut signals associated with appetite, and the only known circulating hormone that triggers a positive energy balance by stimulating food intake. This review summarizes recent findings and several conflicting reports on ghrelin in eating disorders. Understanding these findings and inconsistencies may help in developing new methods to prevent and treat patients with these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Atalayer", "given" : "Deniz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gibson", "given" : "Charlisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konopacka", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geliebter", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Progress in Neuro-Psychopharmacology and Biological Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1", "10" ] ] }, "page" : "70-82", "publisher" : "Elsevier B.V.", "title" : "Ghrelin and eating disorders", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1146/annurev-clinpsy-050212-185546", "ISSN" : "1548-5951", "PMID" : "23537489", "abstract" : "Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.", "author" : [ { "dropping-particle" : "", "family" : "Trace", "given" : "Sara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Jessica H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pe\u00f1as-Lled\u00f3", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Clinical Psychology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "589-620", "title" : "The genetics of eating disorders", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Atalayer et al. 2013; Trace et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Atalayer et al. 2013; Trace et al. 2013). Ghrelin is predominantly produced in the stomach and takes action in the hypothalamus by activating NPY and AgRP containing neurons to increase appetite. A review of the evidence of ghrelin in eating disorders found that in 11 of 16 studies, people with AN had higher ghrelin levels than controls, 6 out 9 studies found that people with BN have no difference in ghrelin levels, and 2 out of 2 studies found that people with BED have less ghrelin than controls ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pnpbp.2012.08.011", "ISSN" : "1878-4216", "PMID" : "22960103", "abstract" : "There is growing evidence supporting a multifactorial etiology that includes genetic, neurochemical, and physiological components for eating disorders above and beyond the more conventional theories based on psychological and sociocultural factors. Ghrelin is one of the key gut signals associated with appetite, and the only known circulating hormone that triggers a positive energy balance by stimulating food intake. This review summarizes recent findings and several conflicting reports on ghrelin in eating disorders. Understanding these findings and inconsistencies may help in developing new methods to prevent and treat patients with these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Atalayer", "given" : "Deniz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gibson", "given" : "Charlisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konopacka", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geliebter", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Progress in Neuro-Psychopharmacology and Biological Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "1", "10" ] ] }, "page" : "70-82", "publisher" : "Elsevier B.V.", "title" : "Ghrelin and eating disorders", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Atalayer et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Atalayer et al. 2013). Further support of the role of ghrelin in eating disorders comes from exogenous ghrelin administration increasing food intake in females with AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1348-4540", "PMID" : "19755753", "abstract" : "Ghrelin increases hunger sensation and food intake in various patients with appetite loss. Anorexia nervosa (AN) begins with psychological stress-induced anorexia and some patients cannot increase their food intake partly because of malnutrition-induced gastrointestinal dysfunction. The effects of ghrelin on appetite, food intake and nutritional parameters in anorexia nervosa (AN) patients were examined. Five female restricting- type AN patients (age: 14-35 y; body mass index: 10.2-14.6 kg/m(2)) had persistently complained of gastrointestinal symptoms and failed to increase body weight. They were hospitalized for 26 days (6 days' pretreatment, 14 days' ghrelin-treatment, and 6 days' post-treatment) and received an intravenous infusion of 3 microg/kg ghrelin twice a day. Ghrelin infusion improved epigastric discomfort or constipation in 4 patients, whose hunger scores evaluated by visual analogue scale questionnaires also increased significantly after ghrelin infusion. Daily energy intake during ghrelin infusion increased by 12-36 % compared with the pre-treatment period. Serum levels of total protein and triglyceride as nutritional parameters significantly increased after ghrelin treatment. There were no serious adverse effects including psychological symptoms. We found that ghrelin decreases gastrointestinal symptoms and increases hunger sensation and daily energy intake without serious adverse events in AN patients. Although the present study had major limitations of the lack of a randomized, placebo-controlled group, non-blindness of the investigators and the small number of patients recruited, it would contribute to further investigations for therapeutic potential of ghrelin in AN patients.", "author" : [ { "dropping-particle" : "", "family" : "Hotta", "given" : "Mari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohwada", "given" : "Rina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akamizu", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shibasaki", "given" : "Tamotsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takano", "given" : "Kazue", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kangawa", "given" : "Kenji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Endocrine Journal", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "page" : "1119-1128", "title" : "Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: a pilot study", "type" : "article-journal", "volume" : "56" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hotta et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hotta et al. 2009). Overall, genetic studies seem to indicate that polymorphisms of the ghrelin gene are not associated with risk of eating disorders. Of 5 studies investigating AN, four found no association between Arg51Gln (rs34911341), Leu72Met (rs696217), Gln90Leu (rs4684677), 3056T>C (rs2075356) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/08039488.2010.525258", "ISSN" : "1502-4725", "PMID" : "21047193", "abstract" : "BACKGROUND: Genetic factors likely contribute to the biological vulnerability of eating disorders. AIMS: Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. METHODS: 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. RESULTS: No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. CONCLUSION: Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.", "author" : [ { "dropping-particle" : "", "family" : "Kindler", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zwaan", "given" : "Martina", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fuchs", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leisch", "given" : "Friedrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gr\u00fcn", "given" : "Bettina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strnad", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stojanovic", "given" : "Mirjana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Windisch", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lennkh-Wolfsberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "El-Giamal", "given" : "Nadja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sieghart", "given" : "Werner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasper", "given" : "Siegfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aschauer", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nordic Journal of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "203-207", "title" : "No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/ajmg.b.30387", "ISSN" : "1552-4841", "PMID" : "16921495", "abstract" : "Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.", "author" : [ { "dropping-particle" : "", "family" : "Ando", "given" : "Tetsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komaki", "given" : "Gen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naruo", "given" : "Tetsuro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okabe", "given" : "Kenjiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takii", "given" : "Masato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Keisuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konjiki", "given" : "Fujiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "Michiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oka", "given" : "Takakazu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Kaori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masuda", "given" : "Akinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozaki", "given" : "Norio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suematsu", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Denda", "given" : "Kenzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurokawa", "given" : "Nobuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Itakura", "given" : "Kotarou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Chikara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kono", "given" : "Masaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "Tatsuyo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakai", "given" : "Yoshikatsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nishizono-Maher", "given" : "Aya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koide", "given" : "Masanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murakami", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagamine", "given" : "Kiyohide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomita", "given" : "Yuichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ookuma", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomita", "given" : "Kazumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tonai", "given" : "Eita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ooshima", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishikawa", "given" : "Toshio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ichimaru", "given" : "Yuhei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Medical Genetics", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2006", "12", "5" ] ] }, "page" : "929-34", "title" : "Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa", "type" : "article-journal", "volume" : "141B" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cellini", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nacmias", "given" : "Benedetta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brecelj-anderluh", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellodi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boni", "given" : "Claudette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Di", "given" : "Daniela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bad\u0131", "given" : "Ana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estivill", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fernandez-aranda", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foulon", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friedel", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabrovsek", "given" : "Mojca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorwood", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gratacos", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guelfi", "given" : "Julien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holliday", "given" : "Jo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Xun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karwautz", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kipman", "given" : "Amelie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komel", "given" : "Radovan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maria", "given" : "Carlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ribases", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ricca", "given" : "Valdo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romo", "given" : "Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomori", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collier", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatric Genetics", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "51-52", "title" : "Case \u2013 control and combined family trios analysis of three polymorphisms in the ghrelin gene in European patients with anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "700" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.neulet.2006.01.023", "ISSN" : "0304-3940", "PMID" : "16472909", "abstract" : "Genetic factors likely contribute to the biological vulnerability to anorexia nervosa (AN) and bulimia nervosa (BN). We investigated whether the Arg51Gln and/or the Leu72Met gene polymorphisms of the human ghrelin, a peptide involved in the regulation of eating behavior, were associated to AN and/or BN. Two-hundred-ninety-two Caucasian women (114 with BN, 59 with AN and 119 healthy controls) participated into the study. No significant differences were found in the frequencies of the Arg51Gln and the Leu72Met ghrelin gene variants among patients with AN or BN and healthy controls. Moreover, no significant differences emerged in eating-related phenotypic variables between patients carrying the Leu72Met genotype as compared to those with the Leu72Leu genotype. These results suggest that the Arg51Gln and the Leu72Met polymorphisms of the human ghrelin gene do not contribute to the genetic susceptibility to AN and BN.", "author" : [ { "dropping-particle" : "", "family" : "Monteleone", "given" : "Palmiero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tortorella", "given" : "Alfonso", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaldo", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filippo", "given" : "Carmela", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maj", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroscience Letters", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2006", "5", "8" ] ] }, "page" : "325-327", "title" : "No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene with anorexia nervosa or bulimia nervosa", "type" : "article-journal", "volume" : "398" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Ando et al. 2006; Cellini et al. 2006; Monteleone et al. 2006; Kindler et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Ando et al. 2006; Cellini et al. 2006; Monteleone et al. 2006; Kindler et al. 2011) and one study found a statistically significant relationship for the transmission of Leu72Met to offspring with AN (p=0.004), including the binging subtype specifically (p=0.005) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.psyneuen.2006.11.003", "ISSN" : "0306-4530", "PMID" : "17197106", "abstract" : "Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.", "author" : [ { "dropping-particle" : "", "family" : "Dardennes", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zizzari", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tolle", "given" : "Virginie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foulon", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kipman", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romo", "given" : "Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iancu-Gontard", "given" : "Dana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boni", "given" : "Claudette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinet", "given" : "Pierre-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Th\u00e9r\u00e8se Bluet", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estour", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mouren", "given" : "Marie-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guelfi", "given" : "Julien-Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rouillon", "given" : "Fr\u00e9d\u00e9ric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorwood", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Epelbaum", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychoneuroendocrinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "2" ] ] }, "page" : "106-113", "title" : "Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and age of onset", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dardennes et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dardennes et al. 2007). Three of four studies investigating BN found no association between Arg51Gln (rs34911341), Leu72Met (rs696217), and Gln90Leu (rs4684677), with BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/08039488.2010.525258", "ISSN" : "1502-4725", "PMID" : "21047193", "abstract" : "BACKGROUND: Genetic factors likely contribute to the biological vulnerability of eating disorders. AIMS: Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. METHODS: 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. RESULTS: No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. CONCLUSION: Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.", "author" : [ { "dropping-particle" : "", "family" : "Kindler", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zwaan", "given" : "Martina", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fuchs", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leisch", "given" : "Friedrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gr\u00fcn", "given" : "Bettina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strnad", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stojanovic", "given" : "Mirjana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Windisch", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lennkh-Wolfsberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "El-Giamal", "given" : "Nadja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sieghart", "given" : "Werner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasper", "given" : "Siegfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aschauer", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nordic Journal of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "203-207", "title" : "No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cellini", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nacmias", "given" : "Benedetta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brecelj-anderluh", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellodi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boni", "given" : "Claudette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Di", "given" : "Daniela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bad\u0131", "given" : "Ana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estivill", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fernandez-aranda", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foulon", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Friedel", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabrovsek", "given" : "Mojca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorwood", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gratacos", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guelfi", "given" : "Julien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holliday", "given" : "Jo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Xun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karwautz", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kipman", "given" : "Amelie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komel", "given" : "Radovan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maria", "given" : "Carlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ribases", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ricca", "given" : "Valdo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romo", "given" : "Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomori", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collier", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatric Genetics", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "51-52", "title" : "Case \u2013 control and combined family trios analysis of three polymorphisms in the ghrelin gene in European patients with anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "700" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.neulet.2006.01.023", "ISSN" : "0304-3940", "PMID" : "16472909", "abstract" : "Genetic factors likely contribute to the biological vulnerability to anorexia nervosa (AN) and bulimia nervosa (BN). We investigated whether the Arg51Gln and/or the Leu72Met gene polymorphisms of the human ghrelin, a peptide involved in the regulation of eating behavior, were associated to AN and/or BN. Two-hundred-ninety-two Caucasian women (114 with BN, 59 with AN and 119 healthy controls) participated into the study. No significant differences were found in the frequencies of the Arg51Gln and the Leu72Met ghrelin gene variants among patients with AN or BN and healthy controls. Moreover, no significant differences emerged in eating-related phenotypic variables between patients carrying the Leu72Met genotype as compared to those with the Leu72Leu genotype. These results suggest that the Arg51Gln and the Leu72Met polymorphisms of the human ghrelin gene do not contribute to the genetic susceptibility to AN and BN.", "author" : [ { "dropping-particle" : "", "family" : "Monteleone", "given" : "Palmiero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tortorella", "given" : "Alfonso", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castaldo", "given" : "Eloisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Filippo", "given" : "Carmela", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Maj", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Neuroscience Letters", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2006", "5", "8" ] ] }, "page" : "325-327", "title" : "No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene with anorexia nervosa or bulimia nervosa", "type" : "article-journal", "volume" : "398" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cellini et al. 2006; Monteleone et al. 2006; Kindler et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cellini et al. 2006; Monteleone et al. 2006; Kindler et al. 2011) and one study conducted in Japanese females found that Leu72Met (rs696217, p=0.0410, OR=1.48, 95%CI: 1.01 to 2.15) and 3056T>C(rs2075356, p=0.0035, OR=1.63, 95%CI: 1.17 to 2.26) are associated with BN as well as an association between all eating disorders and 3056T>C (rs2075356, p=0.0110, OR 1.37, 95%CI: 1.07 to 1.74) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/ajmg.b.30387", "ISSN" : "1552-4841", "PMID" : "16921495", "abstract" : "Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.", "author" : [ { "dropping-particle" : "", "family" : "Ando", "given" : "Tetsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komaki", "given" : "Gen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naruo", "given" : "Tetsuro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okabe", "given" : "Kenjiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takii", "given" : "Masato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Keisuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konjiki", "given" : "Fujiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "Michiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oka", "given" : "Takakazu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "Kaori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Masuda", "given" : "Akinori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ozaki", "given" : "Norio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suematsu", "given" : "Hiroyuki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Denda", "given" : "Kenzo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kurokawa", "given" : "Nobuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Itakura", "given" : "Kotarou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Chikara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kono", "given" : "Masaki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suzuki", "given" : "Tatsuyo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakai", "given" : "Yoshikatsu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nishizono-Maher", "given" : "Aya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koide", "given" : "Masanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murakami", "given" : "Ken", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagamine", "given" : "Kiyohide", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomita", "given" : "Yuichiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ookuma", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomita", "given" : "Kazumi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tonai", "given" : "Eita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ooshima", "given" : "Akira", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishikawa", "given" : "Toshio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ichimaru", "given" : "Yuhei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Medical Genetics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2006", "12", "5" ] ] }, "page" : "929-34", "title" : "Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa", "type" : "article-journal", "volume" : "141B" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Ando et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Ando et al. 2006). Only one study investigated BED and found no association with the SNPs Arg51Gln (rs34911341), Leu72Met (rs696217), Gln90Leu (rs4684677) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/08039488.2010.525258", "ISSN" : "1502-4725", "PMID" : "21047193", "abstract" : "BACKGROUND: Genetic factors likely contribute to the biological vulnerability of eating disorders. AIMS: Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. METHODS: 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. RESULTS: No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. CONCLUSION: Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.", "author" : [ { "dropping-particle" : "", "family" : "Kindler", "given" : "Jochen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bailer", "given" : "Ursula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zwaan", "given" : "Martina", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fuchs", "given" : "Karoline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leisch", "given" : "Friedrich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gr\u00fcn", "given" : "Bettina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strnad", "given" : "Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stojanovic", "given" : "Mirjana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Windisch", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lennkh-Wolfsberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "El-Giamal", "given" : "Nadja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sieghart", "given" : "Werner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kasper", "given" : "Siegfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aschauer", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nordic Journal of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "6" ] ] }, "page" : "203-207", "title" : "No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kindler et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kindler et al. 2011).Brain Derived Neurotrophic Factor (BDNF): BDNF is part of the nerve growth family which binds to a specific receptor, tropomyosin receptor kinase (Trk) B, that is responsible for the growth and regulation of neuronal cells by moderating survival, development, and enhanced synaptic activity in addition to BDNF’s role of modulating neurotransmitters including dopamine, serotonin, and glutamate providing a biological pathway for BDNF to influence food consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/iub.1012", "ISSN" : "1521-6551", "PMID" : "22473707", "abstract" : "Eating disorders (EDs) manifest as abnormal patterns of eating behavior and weight regulation driven by low self-esteem due to weight preoccupation and perceptions toward body weight and shape. Two major groups of such disorders are anorexia nervosa (AN) and bulimia nervosa (BN). The etiology of EDs is complex and evidence indicates that both biological/genetic and psychosocial factors are involved. Several lines of evidence indicate that brain-derived neurotrophic factor (BDNF) plays a critical role in regulating eating behaviors and cognitive impairments in the EDs. BDNF is involved in neuronal proliferation, differentiation, and survival during development. BDNF and its tyrosine kinase receptor (TrkB) are expressed in hypothalamic nuclei associated with eating behaviors. A series of studies using BDNF knockout mice and the human BDNF gene indicate an association of BDNF and EDs with predisposition and vulnerability. In the previous studies, serum BDNF levels in subjects with EDs are reduced significantly compared with healthy controls, hence, we proposed that levels of serum BDNF would be a useful diagnostic indicator for EDs.", "author" : [ { "dropping-particle" : "", "family" : "Nakazato", "given" : "Michiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashimoto", "given" : "Kenji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimizu", "given" : "Eiji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niitsu", "given" : "Tomihisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iyo", "given" : "Masaomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Life", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "page" : "355-361", "title" : "Possible involvement of brain-derived neurotrophic factor in eating disorders", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Nakazato et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Nakazato et al. 2012). Serum BDNF has strong evidence indicating it is positively associated with BMI, however there is conflicting evidence of if BDNF levels increase or decrease in patients with eating disorders ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/iub.1012", "ISSN" : "1521-6551", "PMID" : "22473707", "abstract" : "Eating disorders (EDs) manifest as abnormal patterns of eating behavior and weight regulation driven by low self-esteem due to weight preoccupation and perceptions toward body weight and shape. Two major groups of such disorders are anorexia nervosa (AN) and bulimia nervosa (BN). The etiology of EDs is complex and evidence indicates that both biological/genetic and psychosocial factors are involved. Several lines of evidence indicate that brain-derived neurotrophic factor (BDNF) plays a critical role in regulating eating behaviors and cognitive impairments in the EDs. BDNF is involved in neuronal proliferation, differentiation, and survival during development. BDNF and its tyrosine kinase receptor (TrkB) are expressed in hypothalamic nuclei associated with eating behaviors. A series of studies using BDNF knockout mice and the human BDNF gene indicate an association of BDNF and EDs with predisposition and vulnerability. In the previous studies, serum BDNF levels in subjects with EDs are reduced significantly compared with healthy controls, hence, we proposed that levels of serum BDNF would be a useful diagnostic indicator for EDs.", "author" : [ { "dropping-particle" : "", "family" : "Nakazato", "given" : "Michiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hashimoto", "given" : "Kenji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shimizu", "given" : "Eiji", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Niitsu", "given" : "Tomihisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iyo", "given" : "Masaomi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Life", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "page" : "355-361", "title" : "Possible involvement of brain-derived neurotrophic factor in eating disorders", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Nakazato et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Nakazato et al. 2012). Further evidence of the role of BDNF in food consumption behaviours comes from studies of humans with mutation deletions in the BDNF region. Individuals with the deletion mutation suffer from extreme hyperphagia and obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db06-0550", "ISSN" : "0012-1797", "PMID" : "17130481", "abstract" : "The neurotrophin brain-derived neurotrophic factor (BDNF) inhibits food intake, and rodent models of BDNF disruption all exhibit increased food intake and obesity, as well as hyperactivity. We report an 8-year-old girl with hyperphagia and severe obesity, impaired cognitive function, and hyperactivity who harbored a de novo chromosomal inversion, 46,XX,inv(11)(p13p15.3), a region encompassing the BDNF gene. We have identified the proximal inversion breakpoint that lies 850 kb telomeric of the 5' end of the BDNF gene. The patient's genomic DNA was heterozygous for a common coding polymorphism in BDNF, but monoallelic expression was seen in peripheral lymphocytes. Serum concentration of BDNF protein was reduced compared with age- and BMI-matched subjects. Haploinsufficiency for BDNF was associated with increased ad libitum food intake, severe early-onset obesity, hyperactivity, and cognitive impairment. These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior.", "author" : [ { "dropping-particle" : "", "family" : "Gray", "given" : "Juliette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yeo", "given" : "Giles S H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "James J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morton", "given" : "Jenny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adlam", "given" : "Anna-Lynne R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keogh", "given" : "Julia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Jack a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gharbawy", "given" : "Areeg", "non-dropping-particle" : "El", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Joan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tung", "given" : "Y C Loraine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hodges", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raymond", "given" : "F Lucy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2006", "12" ] ] }, "page" : "3366-3371", "title" : "Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1056/NEJMoa0801119", "ISSN" : "1533-4406", "PMID" : "18753648", "abstract" : "BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been found to be important in energy homeostasis in animal models, but little is known about its role in energy balance in humans. Heterozygous, variably sized, contiguous gene deletions causing haploinsufficiency of the WT1 and PAX6 genes on chromosome 11p13, approximately 4 Mb centromeric to BDNF (11p14.1), result in the Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome. Hyperphagia and obesity were observed in a subgroup of patients with the WAGR syndrome. We hypothesized that the subphenotype of obesity in the WAGR syndrome is attributable to deletions that induce haploinsufficiency of BDNF. METHODS: We studied the relationship between genotype and body-mass index (BMI) in 33 patients with the WAGR syndrome who were recruited through the International WAGR Syndrome Association. The extent of each deletion was determined with the use of oligonucleotide comparative genomic hybridization. RESULTS: Deletions of chromosome 11p in the patients studied ranged from 1.0 to 26.5 Mb; 58% of the patients had heterozygous BDNF deletions. These patients had significantly higher BMI z scores throughout childhood than did patients with intact BDNF (mean [+/-SD] z score at 8 to 10 years of age, 2.08+/-0.45 in patients with heterozygous BDNF deletions vs. 0.88+/-1.28 in patients without BDNF deletions; P=0.03). By 10 years of age, 100% of the patients with heterozygous BDNF deletions (95% confidence interval [CI], 77 to 100) were obese (BMI > or = 95th percentile for age and sex) as compared with 20% of persons without BDNF deletions (95% CI, 3 to 56; P<0.001). The critical region for childhood-onset obesity in the WAGR syndrome was located within 80 kb of exon 1 of BDNF. Serum BDNF concentrations were approximately 50% lower among the patients with heterozygous BDNF deletions (P=0.001). CONCLUSIONS: Among persons with the WAGR syndrome, BDNF haploinsufficiency is associated with lower levels of serum BDNF and with childhood-onset obesity; thus, BDNF may be important for energy homeostasis in humans.", "author" : [ { "dropping-particle" : "", "family" : "Han", "given" : "Joan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Qing-Rong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "MaryPat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levinn", "given" : "Rebecca L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Menzie", "given" : "Carolyn M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jefferson-George", "given" : "Kyra S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adler-Wailes", "given" : "Diane C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanford", "given" : "Ethan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lacbawan", "given" : "Felicitas L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uhl", "given" : "George R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rennert", "given" : "Owen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Jack a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The New England Journal of Medicine", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2008", "8", "28" ] ] }, "page" : "918-927", "title" : "Brain-derived neurotrophic factor and obesity in the WAGR syndrome", "type" : "article-journal", "volume" : "359" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gray et al. 2006; Han et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gray et al. 2006; Han et al. 2008).A 2007 meta-analysis of the effect of BDNF Val66Met (rs6265) including five studies estimated that individuals with the Met/Met or Met/Val genotypes have a 36% greater chance of developing an eating disorder than those with the Val/Val genotype. Though the pooled effect was positive, only two of the five studies had statistically significant results and one of the studies had a negative association ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.biopsych.2006.08.025", "ISSN" : "0006-3223", "PMID" : "17217930", "abstract" : "BACKGROUND: There is an increasing recognition that the pathophysiology of mental disorders could be the result of deregulation of synaptic plasticity with alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant, located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been extensively studied through linkage and association approaches in several psychiatric disorders. METHODS: We performed a meta-analysis restricted to individual case-control studies in different categories of mental disorders and BDNF Val66Met polymorphism. We included data from 39 case-control studies encompassing psychiatric phenotypes: eating disorders, substance-related disorders, mood disorders, and schizophrenia, among others. RESULTS: The association of Val66Met was confined to three diagnoses: substance-related disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met genotypes increase the risk for eating disorders up to 33%, while these same genotypes confer a 21% protective effect in substance-related disorders. The homozygous carriers Met/Met showed a 19% increased risk of schizophrenia with respect to the heterozygous state. CONCLUSIONS: The study confirms the association of Val66Met to substance-related disorders, eating disorders, and schizophrenia. It remains to be determined if other variants in tight linkage disequilibrium with Val66Met could configure an extended functional haplotype that would explain observed discrepancies in risk estimations across studies.", "author" : [ { "dropping-particle" : "", "family" : "Gratac\u00f2s", "given" : "M\u00f2nica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez", "given" : "Juan R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mercader", "given" : "Josep M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cid", "given" : "Rafael", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Urretavizcaya", "given" : "Mikel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estivill", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2007", "4", "1" ] ] }, "page" : "911-922", "title" : "Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gratac\u00f2s et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gratacòs et al. 2007). Since the meta-analysis, further studies have yielded inconclusive results. For Val66Met (rs6265) specifically, four out of five studies investigating the gene found no statistically significant relationship with AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.psyneuen.2006.11.003", "ISSN" : "0306-4530", "PMID" : "17197106", "abstract" : "Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.", "author" : [ { "dropping-particle" : "", "family" : "Dardennes", "given" : "Roland M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zizzari", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tolle", "given" : "Virginie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foulon", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kipman", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Romo", "given" : "Lucia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iancu-Gontard", "given" : "Dana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boni", "given" : "Claudette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sinet", "given" : "Pierre-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Th\u00e9r\u00e8se Bluet", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estour", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mouren", "given" : "Marie-Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guelfi", "given" : "Julien-Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rouillon", "given" : "Fr\u00e9d\u00e9ric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorwood", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Epelbaum", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychoneuroendocrinology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007", "2" ] ] }, "page" : "106-113", "title" : "Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and age of onset", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00787-013-0495-6", "ISBN" : "0078701304956", "ISSN" : "1435-165X", "PMID" : "24292283", "abstract" : "The brain-derived neurotrophic factor (BDNF) gene may influence eating behavior, body weight and cognitive impairments. We aimed to investigate whether BDNF genetic variability may affect anthropometric and psychological parameters in patients with anorexia or bulimia nervosa (AN, BN) and/or modulate the risk for the disorder. A total of 169 unrelated female patients and 312 healthy controls were genotyped for two common BDNF single-nucleotide polymorphisms (SNPs), Val66Met and C-270T, and several selected tag-SNPs. Associated personality characteristics and psychopathological symptoms were assessed by the EDI-2 and SCL-90R inventories, respectively. No single SNP or haplotype played a relevant role in the risk for AN or BN. The rs16917237 TT genotype was significantly associated with increased weight (74.63 \u00b1 16.58 vs. 57.93 \u00b1 13.02) and body mass index (28.94 \u00b1 6.22 vs. 22.23 \u00b1 4.77) in the BN group after correcting for multiple testing. Haplotype analyses using a sliding window approach with three adjacent SNPs produced four loci of interest. Locus 3 (rs10835210/rs16917237/C-270T) showed a broad impact on the measured psychopathological symptoms. Haplotypes CGC and CGT in this locus correlated with scores in all three scales of the SCL-90R inventory, both in AN and BN patients. In contrast, the results of the EDI-2 inventory were largely unaffected. These preliminary results suggest that variability in the BDNF gene locus may contribute to anthropometric characteristics and also psychopathological symptoms that are common but not exclusive of ED patients.", "author" : [ { "dropping-particle" : "", "family" : "Gamero-Villarroel", "given" : "Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordillo", "given" : "Inmaculada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrillo", "given" : "Juan Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Herr\u00e1iz", "given" : "Angustias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flores", "given" : "Isalud", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez", "given" : "Mercedes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monge", "given" : "Melchora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodr\u00edguez-L\u00f3pez", "given" : "Raquel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gervasini", "given" : "Guillermo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Child & Adolescent Psychiatry", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "11", "29" ] ] }, "title" : "BDNF genetic variability modulates psychopathological symptoms in patients with eating disorders", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/ajmg.b.32000", "ISSN" : "1552-485X", "PMID" : "22127997", "abstract" : "The Met66 allele of the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785-1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one-way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.", "author" : [ { "dropping-particle" : "", "family" : "Ando", "given" : "Tetsuya", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ishikawa", "given" : "Toshio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotta", "given" : "Mari", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Naruo", "given" : "Tetsuro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okabe", "given" : "Kenjiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakahara", "given" : "Toshihiro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takii", "given" : "Masato", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kawai", "given" : "Keisuke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mera", "given" : "Takashi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nakamoto", "given" : "Chiemi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takei", "given" : "Michiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamaguchi", "given" : "Chikara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nagata", "given" : "Toshihiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Okamoto", "given" : "Yuri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ookuma", "given" : "Kazuyoshi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koide", "given" : "Masanori", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yamanaka", "given" : "Takao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Murata", "given" : "Shiho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tamura", "given" : "Naho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiriike", "given" : "Nobuo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ichimaru", "given" : "Yuhei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komaki", "given" : "Gen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Medical Genetics", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "48-52", "title" : "No association of brain-derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese", "type" : "article-journal", "volume" : "159B" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.3109/15622975.2011.605470", "ISSN" : "1814-1412", "PMID" : "21936709", "abstract" : "OBJECTIVES: The Val66Met polymorphism (rs6265) of the BDNF gene is a non-synonymous polymorphism, previously associated with anorexia nervosa (AN). METHODS: We genotyped rs6265 in 235 patients with AN and 643 controls. Furthermore, we performed a systematic review of all case-control and family-based studies testing this SNP in AN, and combined the results in a meta-analysis. RESULTS: The results of the case-control study were non-significant. For the meta-analysis, nine studies were identified (ncases = 2,767; ncontrols = 3,322, ntrios = 53) and included. Primarily, the analyses indicated an association with OR of 1.11 (P = 0.024) in the allelic contrast, and OR of 1.14 (P = 0.025) for the dominant effect of the Met allele. However, additional analyses revealed that the first published study (from those included in the meta-analysis) overly influenced the pooled effect size (possibly due to a phenomenon known as a winner's curse). When this case-control study was replaced by a trio study (ntrios = 293) performed on a largely overlapping sample, the effect size became smaller and non-significant, both for the allelic contrast (OR = 1.07, P = 0.156) and the dominant effect (OR = 1.07, P = 0.319). The quality of included studies was good and there was no significant heterogeneity across the effect sizes. CONCLUSIONS: Our analyses indicate that the BDNF Val66Met variant is not associated with AN at detectable levels.", "author" : [ { "dropping-particle" : "", "family" : "Brandys", "given" : "Marek K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kas", "given" : "Martien J H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elburg", "given" : "Annemarie a", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ophoff", "given" : "Roel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slof-Op't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Middeldorp", "given" : "Christel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "Roger a H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The World Journal of Biological Psychiatry", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "441-451", "title" : "The Val66Met polymorphism of the BDNF gene in anorexia nervosa: new data and a meta-analysis", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dardennes et al. 2007; Ando et al. 2012; Brandys et al. 2013; Gamero-Villarroel et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dardennes et al. 2007; Ando et al. 2012; Brandys et al. 2013; Gamero-Villarroel et al. 2013) and the study with the positive outcome for Val66Met (rs6265) as well as rs2030324 was no longer significant after adjusting for multiple testing (p-values between 0.002 to 0.21 for genotypes and 0.00 to 0.039 for alleles) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.psychres.2012.09.005", "ISSN" : "1872-7123", "PMID" : "23107791", "abstract" : "In this research, we conducted a study of genes connected with the neurodevelopmental hypothesis of anorexia nervosa, using classical statistical and data-mining methods to establish a relationship with disease risk and algorithms to identify the best genetic predictors of anorexia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Dmitrzak-Weglarz", "given" : "Monika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moczko", "given" : "Jerzy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skibinska", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slopien", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tyszkiewicz", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pawlak", "given" : "Joanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zaremba", "given" : "Dorota", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Szczepankiewicz", "given" : "Aleksandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rajewski", "given" : "Andrzej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hauser", "given" : "Joanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatry Research", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "3", "30" ] ] }, "page" : "117-121", "publisher" : "Elsevier", "title" : "The study of candidate genes related to the neurodevelopmental hypothesis of anorexia nervosa: classical association study versus decision tree", "type" : "article-journal", "volume" : "206" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dmitrzak-Weglarz et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dmitrzak-Weglarz et al. 2013). Two studies published prior to the meta-analysis but not included found positive associations between the Met allele of the Val66Met BDNF polymorphism and restricting type AN and minimum BMI in a Spanish population ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/sj.mp.4001281", "ISSN" : "1359-4184", "PMID" : "12888803", "abstract" : "Several lines of evidence support a role for brain-derived neurotrophic factor (BDNF) alterations in the etiology of eating disorders (EDs). BDNF heterozygous knockout mice show alterations in eating behavior, increased body weight and adipocyte hypertrophy. BDNF also regulates the synaptic efficiency through the modulation of key neurotransmitter systems previously known to be involved in ED. These findings, together with the fact that this neurotrophin is expressed in the hypothalamus nuclei associated with weight regulation and feeding control, led us to propose BDNF as a candidate gene for ED. To investigate the possible involvement of this neurotrophin in eating behavior, we screened the BDNF gene in 95 ED patients and identified four sequence variants. Two of them, -374A/T and -256G/A, were found in two patients with anorexia nervosa (AN) and consisted of single-nucleotide mutations within the 5' untranslated region (5'UTR). The other two polymorphisms resulted in a C to T transition located at the 5'UTR of the BDNF gene and an amino-acid substitution within the BDNF precursor protein (Val66Met). We performed a case-control study for these two Single-nucleotide polymorphisms in a sample of 143 ED patients and 112 unrelated controls and found a strong association of restricting AN (ANR) with the Met allele of the Val66Met BDNF polymorphism (2p=0.002). There was also evidence for a significant effect of this sequence variant on the minimum body mass index (MBMI) (2p=0.006). These results suggest that the BDNF Met66 variant may be a susceptibility factor to ED, mainly to ANR and low MBMI.", "author" : [ { "dropping-particle" : "", "family" : "Ribas\u00e9s", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gratac\u00f2s", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Armengol", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cid", "given" : "R", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bad\u00eda", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solano", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vallejo", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fern\u00e1ndez", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estivill", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular Psychiatry", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2003", "8" ] ] }, "page" : "745-751", "title" : "Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Ribas\u00e9s et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Ribasés et al. 2003) and a positive association between the Met allele of the Val66Met BDNF polymorphism and restrictive type AN, and minimum BMI ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/sj.ejhg.5201351", "ISSN" : "1018-4813", "PMID" : "15657604", "abstract" : "Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.", "author" : [ { "dropping-particle" : "", "family" : "Ribas\u00e9s", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gratac\u00f2s", "given" : "M\u00f2nica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fern\u00e1ndez-Aranda", "given" : "Fernando", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bellodi", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boni", "given" : "Claudette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderluh", "given" : "Marija", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cristina Cavallini", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cellini", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bella", "given" : "Daniela", "non-dropping-particle" : "Di", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erzegovesi", "given" : "Stefano", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Foulon", "given" : "Christine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gabrovsek", "given" : "Mojca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gorwood", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holliday", "given" : "Jo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Xun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karwautz", "given" : "Andreas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kipman", "given" : "Am\u00e9lie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Komel", "given" : "Radovan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nacmias", "given" : "Benedetta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Remschmidt", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ricca", "given" : "Valdo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorbi", "given" : "Sandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tomori", "given" : "Martina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagner", "given" : "Gudrun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collier", "given" : "David a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estivill", "given" : "Xavier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Journal of Human Genetics", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2005", "4" ] ] }, "page" : "428-434", "title" : "Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Ribas\u00e9s et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Ribasés et al. 2005). One study found a positive result for BDNF (rs7934165A/270T) and AN (p=0.008) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1601-183X.2007.00301.x", "ISSN" : "1601-1848", "PMID" : "17376155", "abstract" : "Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.", "author" : [ { "dropping-particle" : "", "family" : "Mercader", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ribas\u00e9s", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gratac\u00f2s", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bay\u00e9s", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cid", "given" : "R", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bad\u00eda", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fern\u00e1ndez-Aranda", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estivill", "given" : "X", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genes, Brain and Behavior", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "11" ] ] }, "page" : "706-716", "title" : "Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mercader et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mercader et al. 2007). Addition BDNF SNPs that were found to not have an association include rs11030102, rs10835210, rs16917237, rs56164415, and rs11030119 with both AN and BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00787-013-0495-6", "ISBN" : "0078701304956", "ISSN" : "1435-165X", "PMID" : "24292283", "abstract" : "The brain-derived neurotrophic factor (BDNF) gene may influence eating behavior, body weight and cognitive impairments. We aimed to investigate whether BDNF genetic variability may affect anthropometric and psychological parameters in patients with anorexia or bulimia nervosa (AN, BN) and/or modulate the risk for the disorder. A total of 169 unrelated female patients and 312 healthy controls were genotyped for two common BDNF single-nucleotide polymorphisms (SNPs), Val66Met and C-270T, and several selected tag-SNPs. Associated personality characteristics and psychopathological symptoms were assessed by the EDI-2 and SCL-90R inventories, respectively. No single SNP or haplotype played a relevant role in the risk for AN or BN. The rs16917237 TT genotype was significantly associated with increased weight (74.63 \u00b1 16.58 vs. 57.93 \u00b1 13.02) and body mass index (28.94 \u00b1 6.22 vs. 22.23 \u00b1 4.77) in the BN group after correcting for multiple testing. Haplotype analyses using a sliding window approach with three adjacent SNPs produced four loci of interest. Locus 3 (rs10835210/rs16917237/C-270T) showed a broad impact on the measured psychopathological symptoms. Haplotypes CGC and CGT in this locus correlated with scores in all three scales of the SCL-90R inventory, both in AN and BN patients. In contrast, the results of the EDI-2 inventory were largely unaffected. These preliminary results suggest that variability in the BDNF gene locus may contribute to anthropometric characteristics and also psychopathological symptoms that are common but not exclusive of ED patients.", "author" : [ { "dropping-particle" : "", "family" : "Gamero-Villarroel", "given" : "Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gordillo", "given" : "Inmaculada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carrillo", "given" : "Juan Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garc\u00eda-Herr\u00e1iz", "given" : "Angustias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flores", "given" : "Isalud", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez", "given" : "Mercedes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monge", "given" : "Melchora", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodr\u00edguez-L\u00f3pez", "given" : "Raquel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gervasini", "given" : "Guillermo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Child & Adolescent Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "11", "29" ] ] }, "title" : "BDNF genetic variability modulates psychopathological symptoms in patients with eating disorders", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gamero-Villarroel et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gamero-Villarroel et al. 2013), and rs712442, rs11030107, rs7103873, rs11030123, rs17309930, rs2049048, and rs1491851 with AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1111/j.1601-183X.2010.00660.x", "ISSN" : "1601-183X", "PMID" : "20946355", "abstract" : "Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self-induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71-91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain-derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P-values < 0.05 from this initial study were then tested for replication in a meta-analysis with two additional independent ED case-control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C-allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08-1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28-2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16-1.64, P < 0.0003). The meta-analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "M C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Suchiman", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Middeldorp", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Houwing-Duistermaat", "given" : "J J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trier", "given" : "J", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Onkenhout", "given" : "E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vink", "given" : "J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beijsterveldt", "given" : "C E M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brandys", "given" : "M K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanders", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zipfel", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzog", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpertz-Dahlmann", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klampfl", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fleischhaker", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zeeck", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zwaan", "given" : "M", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpertz", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehrlich", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elburg", "given" : "a a", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "R a H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scherag", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "D I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "E F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genes, Brain, and Behavior", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2011", "3" ] ] }, "page" : "236-243", "title" : "Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting", "type" : "article-journal", "volume" : "10" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Slof-Op \u2019t Landt et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Slof-Op ’t Landt et al. 2011)Other Mechanisms: There are other proposed mechanisms that may have genetic links to eating disorders though they are less well studied. Cholecystokinin, a hormone which decreases appetite through receptors in the CNS as well as stimulating the digestion of lipids and proteins in the small intestine has had suggestive evidence linking it to AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.brainresrev.2009.10.007", "ISSN" : "1872-6321", "PMID" : "19931559", "abstract" : "Anorexia nervosa (AN) is a complex multi-factorial disease with high heritability. The psychological AN symptoms are poorly connected with specific molecular mechanisms. Here we review the molecular basis of AN with the focus on human genetic association studies; we put these in the experimental biological context with emphasis on molecular systems controlling food intake and body weight in a direct or indirect manner. We systematically searched for human genetic studies related to AN and grouped data into main categories/systems reflecting their major known roles: (1) Systems related to mental disorders (serotonin, brain-derived neurotrophic factor (BDNF), norepinephrine (NE), glutamate (NMDA) receptor and SK3 channel, KCCN3). (2) Hunger regulatory systems (leptin, AGRP, MSH, melanocortin 4 receptor (MC4R), NPY, ghrelin, cholecystokinin (CCK). (3) Feeding motivation- and reward-related systems (opioids, OPRD1, cannabinoids (anandamide (AEA), THC, CBR1), dopamine, DRD2, DRD3, DRD4, catecholamine-O-methyl transferase (COMT). (4) Systems regulating energy metabolism (uncoupling proteins 2 and 3 (UCP2 and UCP3). (5) Neuroendocrine systems with emphasis on sex hormones (estrogen receptor-beta (ESR2). (6) The immune system and inflammatory response (tumor necrosis factor-alpha (TNF-alpha)). Overall, we found that in total 175 association studies have been performed on AN cohorts on 128 different polymorphisms related to 43 genes. We review the strongest associations, identify some genes that have an important role in regulating BMI whose possible relationship to AN has not been investigated and discuss the potential targets for pharmacological interventions.", "author" : [ { "dropping-particle" : "", "family" : "Rask-Andersen", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olszewski", "given" : "Pawel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Allen S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f6th", "given" : "Helgi B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain Research Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "147-164", "publisher" : "Elsevier B.V.", "title" : "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rask-Andersen et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rask-Andersen et al. 2010). Glutamate receptor (NMDAr) also plays a role in eating behaviour through its action on the reward system for food consumption and is associated with the SK3 Channel which in the brain, regulates the ion flow through the NMDA receptor. Genes coding for SK3 and NMDAr have both been shown to be associated with AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.brainresrev.2009.10.007", "ISSN" : "1872-6321", "PMID" : "19931559", "abstract" : "Anorexia nervosa (AN) is a complex multi-factorial disease with high heritability. The psychological AN symptoms are poorly connected with specific molecular mechanisms. Here we review the molecular basis of AN with the focus on human genetic association studies; we put these in the experimental biological context with emphasis on molecular systems controlling food intake and body weight in a direct or indirect manner. We systematically searched for human genetic studies related to AN and grouped data into main categories/systems reflecting their major known roles: (1) Systems related to mental disorders (serotonin, brain-derived neurotrophic factor (BDNF), norepinephrine (NE), glutamate (NMDA) receptor and SK3 channel, KCCN3). (2) Hunger regulatory systems (leptin, AGRP, MSH, melanocortin 4 receptor (MC4R), NPY, ghrelin, cholecystokinin (CCK). (3) Feeding motivation- and reward-related systems (opioids, OPRD1, cannabinoids (anandamide (AEA), THC, CBR1), dopamine, DRD2, DRD3, DRD4, catecholamine-O-methyl transferase (COMT). (4) Systems regulating energy metabolism (uncoupling proteins 2 and 3 (UCP2 and UCP3). (5) Neuroendocrine systems with emphasis on sex hormones (estrogen receptor-beta (ESR2). (6) The immune system and inflammatory response (tumor necrosis factor-alpha (TNF-alpha)). Overall, we found that in total 175 association studies have been performed on AN cohorts on 128 different polymorphisms related to 43 genes. We review the strongest associations, identify some genes that have an important role in regulating BMI whose possible relationship to AN has not been investigated and discuss the potential targets for pharmacological interventions.", "author" : [ { "dropping-particle" : "", "family" : "Rask-Andersen", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olszewski", "given" : "Pawel K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Allen S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schi\u00f6th", "given" : "Helgi B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brain Research Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010", "3" ] ] }, "page" : "147-164", "publisher" : "Elsevier B.V.", "title" : "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rask-Andersen et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rask-Andersen et al. 2010).2.7.5 Summary Though there is an undeniable genetic component to the development of eating disorders, with heritability estimates from twin studies ranging from 0.28 to 0.76 for AN and 0.30 to 0.83 for BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-953X", "PMID" : "10698815", "abstract" : "OBJECTIVE: Lifetime rates of full and partial anorexia nervosa and bulimia nervosa were determined in first-degree relatives of diagnostically pure proband groups and relatives of matched, never-ill comparison subjects. METHOD: Rates of each eating disorder were obtained for 1,831 relatives of 504 probands on the basis of personal structured clinical interviews and family history. Best-estimate diagnoses based on all available information were rendered without knowledge of proband status and pedigree identity. Only definite and probable diagnoses were considered. RESULTS: Whereas anorexia nervosa was rare in families of the comparison subjects, full and partial syndromes of anorexia nervosa aggregated in female relatives of both anorexic and bulimic probands. For the full syndrome of anorexia nervosa, the relative risks were 11.3 and 12.3 in female relatives of anorexic and bulimic probands, respectively. Bulimia nervosa was more common than anorexia nervosa in female relatives of comparison subjects, but it, too, aggregated in the families of ill probands; the corresponding relative risks for bulimia nervosa were 4.2 and 4.4 for female relatives of anorexic and bulimic probands, respectively. When partial syndromes of anorexia nervosa and bulimia nervosa were considered, relative risks fell by one-half in each group of ill probands. CONCLUSIONS: Both anorexia nervosa and bulimia nervosa are familial. Their cross-transmission in families suggests a common, or shared, familial diathesis. The additional observation that familial aggregation and cross-transmission extend to milder phenotypes suggests the validity of their inclusion in a continuum of familial liability.", "author" : [ { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freeman", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lampert", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diamond", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2000", "3" ] ] }, "page" : "393-401", "title" : "Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes", "type" : "article-journal", "volume" : "157" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0193-953X", "PMID" : "11416922", "abstract" : "Data described earlier are clear in establishing a role for genes in the development of eating abnormalities. Estimates from the most rigorous studies suggest that more than 50% of the variance in eating disorders and disordered eating behaviors can be accounted for by genetic effects. These high estimates indicate a need for studies identifying the specific genes contributing to this large proportion of variance. Twin and family studies suggest that several heritable characteristics that are commonly comorbid with AN and BN may share genetic transmission with these disorders, including anxiety disorders or traits, body weight, and possibly major depression. Moreover, some developmental research suggests that the genes involved in ovarian hormones or the genes that these steroids affect also may be genetically linked to eating abnormalities. Molecular genetic research of these disorders is in its infant stages. However, promising areas for future research have already been identified (e.g., 5-HT2A receptor gene, UCP-2/UCP-3 gene, and estrogen receptor beta gene), and several large-scale linkage and association studies are underway. These studies likely will provide invaluable information regarding the appropriate phenotypes to be included in genetic studies and the genes with the most influence on the development of these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Klump", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychiatric Clinics of North America", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2001", "6" ] ] }, "page" : "215-225", "title" : "The evolving genetic foundations of eating disorders", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Strober et al. 2000; Klump et al. 2001)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Strober et al. 2000; Klump et al. 2001), and between 0.41 to 0.57 for BED ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/7854", "author" : [ { "dropping-particle" : "", "family" : "Thornton", "given" : "Laura M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mazzeo", "given" : "Suzanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Topics in Behavioral Neuroscience", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "141-156", "title" : "The heritability of eating disorders: Methods and current findings", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Thornton et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Thornton et al. 2011). Our review of genetic association studies found very little evidence supporting the role of functional variants in genes that may influence eating disorders. There was inconclusive evidence for genes related to serotonin (5-HT2A, 5-HTTLPR, 5-HT1B, 5-HT1DB, 5-HT2C, 5-HTR3B, 5-HT1D, 5-HT7), dopamine (DRD2, DRD3, DRD4, COMT), norepinephrine (NET), and peptide YY with studies finding a range of negative, positive, and no effect results. Genes associated with Neuropeptide Y, Leptin (LEPR), and ghrelin, had evidence indicating a lack of association with eating disorders while AGRP was found to have a possible association with AN, MC4R a possible association with BED, and BDNF with all eating disorders. The strongest evidence was for OPRD1 (opioid receptor) with AN. 3.0 Justification and Objectives As the prevalence of obesity continues to increase worldwide ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(10)62037-5", "ISSN" : "1474-547X", "PMID" : "21295846", "abstract" : "Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI.", "author" : [ { "dropping-particle" : "", "family" : "Finucane", "given" : "Mariel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Gretchen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowan", "given" : "Melanie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danaei", "given" : "Goodarz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "John K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paciorek", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Gitanjali M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutierrez", "given" : "Hialy R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bahalim", "given" : "Adil N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farzadfar", "given" : "Farshad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Leanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ezzati", "given" : "Majid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9765", "issued" : { "date-parts" : [ [ "2011", "2", "12" ] ] }, "page" : "557-567", "publisher" : "Elsevier Ltd", "title" : "National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9\u00b71 million participants.", "type" : "article-journal", "volume" : "377" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Finucane et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Finucane et al. 2011), there is a dire need to better understand the disease to curb the obesity epidemic and help prevent health complications ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.pop.2009.01.009", "ISSN" : "1558-299X", "PMID" : "19501243", "abstract" : "Obesity, especially visceral adiposity, is associated with morbidity and mortality through endocrine and mechanical processes. Clinical manifestations due to effects of obesity on the cardiovascular, respiratory, gastrointestinal, musculoskeletal, immune, and integumentary systems have been described. Further studies are needed to understand the pathologic processes underlying these clinical manifestations to improve disease prevention.", "author" : [ { "dropping-particle" : "", "family" : "Schelbert", "given" : "Kavitha Bhat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Prim Care Clin Office Pract", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "6" ] ] }, "page" : "271-285", "publisher" : "Elsevier Ltd", "title" : "Comorbidities of obesity", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Schelbert 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Schelbert 2009), decreases in life expectancy ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fontaine", "given" : "Kevin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Redden", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Chenxi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westfall", "given" : "Andrew O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Med Assoc", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "187-193", "title" : "Years of life lost due to obesity", "type" : "article-journal", "volume" : "289" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fontaine et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fontaine et al. 2003), and reduce the economic burden ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.beem.2013.01.002", "ISSN" : "1878-1594", "PMID" : "23731873", "abstract" : "Obesity has substantially increased in recent decades and is now one of the major global health problems. The large obesity-related health burden negatively impacts many relevant health outcomes (e.g. quality of life, disability, mortality) and leads to increased healthcare utilization. This excess service use is the main driver behind high healthcare costs of obese individuals. Findings indicate that costs rise curvilinearly with increasing body mass index, especially among the obese. As more individuals of a country's population become obese, a larger share of total annual national healthcare expenditure is spent on obesity and obesity-related health problems. In addition to escalating healthcare costs, obesity goes along with indirect costs through decreases in workforce productivity. The empirical evidence has shown beyond doubt that obesity negatively impacts individuals, healthcare systems, employers, and the economy as a whole. This article provides a brief overview of selected economic consequences associated with excess-weight.", "author" : [ { "dropping-particle" : "", "family" : "Lehnert", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonntag", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Konnopka", "given" : "Alexander", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riedel-Heller", "given" : "Steffi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6nig", "given" : "Hans-Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Best practice & research. Clinical endocrinology & metabolism", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2013", "4" ] ] }, "page" : "105-115", "title" : "Economic costs of overweight and obesity", "type" : "article-journal", "volume" : "27" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Lehnert et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Lehnert et al. 2013). Obesity treatments fall on spectrum of effectiveness. Lifestyle interventions are very limited in their success, pharmacotherapy options are successful in some cases, and bariatric surgeries can lead to significant weight loss. However, the more effective the treatment, the higher the risk for serious complications ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2012-3115", "ISSN" : "1945-7197", "PMID" : "23443815", "abstract" : "Obesity is a disease that is defined as the accumulation of excessive amounts of body fat and is associated with increased risk of serious illness, disability, and death. In clinical practice, obesity is best assessed by calculating body mass index and measuring waist circumference. Treatment options are determined based on the body mass index, waist circumference, and adverse health consequences the patient is experiencing or is at an increased risk for facing in the future. Today, overweight and obesity impacts the majority of patients we treat in our clinical practices. Although endocrinologists are uniquely positioned to treat one of the major consequences of our current obesity epidemic, type 2 diabetes, we also need to be positioned and prepared to effectively treat one of its major causes-obesity. Type 2 diabetes and obesity are very much intertwined. Treatment of each disease affects the other. For these reasons, endocrinologists need to be experts in the treatment of obesity as well as diabetes. They should keep up with advances in obesity treatment including lifestyle, pharmaceutical, and surgical strategies. These strategies offer opportunities for improving the overall treatment for our obese patients today and will continue to improve and expand over the next decade.", "author" : [ { "dropping-particle" : "", "family" : "Wyatt", "given" : "Holly R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "4" ] ] }, "page" : "1299-306", "title" : "Update on treatment strategies for obesity.", "type" : "article-journal", "volume" : "98" }, "uris" : [ "", "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1467-789X.2011.00981.x", "ISSN" : "1467-789X", "PMID" : "22288431", "abstract" : "The study aims to compare anti-obesity interventions in a single evidence synthesis framework. Electronic databases were searched for randomized controlled trials of orlistat, rimonabant or sibutramine reporting weight or body mass index (BMI) change from baseline at 3, 6 or 12 months. A mixed treatment comparison was used to combine direct and indirect trial evidence. Ninety-four studies involving 24,808 individuals were included; 83 trials included data on weight change and 41 on BMI change. All results are in comparison with placebo. The active drugs were all effective at reducing weight and BMI. At 3 months, orlistat reduced weight by -2.65 kg (95% credibility interval -4.00 kg, -1.31 kg). For sibutramine, 15 mg gave a greater reduction than 10 mg at 12 months, -6.35 kg versus -5.42 kg, respectively. Rimonabant reduced weight by -11.23 kg at 3 months and -4.55 kg at 12 months. Lifestyle advice alone also reduced weight at 6 and 12 months, but was less effective than the pharmacological interventions. In conclusion, modest weight reductions were seen for all pharmacological interventions. Those interventions which have now been withdrawn from use (sibutramine and rimonabant) seem to be the most effective, implying that there may be a place in clinical practice for similar drugs if side effects could be avoided.", "author" : [ { "dropping-particle" : "", "family" : "Gray", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dunkley", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warren", "given" : "F C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ara", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abrams", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khunti", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutton", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity reviews : an official journal of the International Association for the Study of Obesity", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "6" ] ] }, "page" : "483-98", "title" : "A systematic review and mixed treatment comparison of pharmacological interventions for the treatment of obesity.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "", "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gray et al. 2012; Wyatt 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gray et al. 2012; Wyatt 2013). Investigating methods of preventing obesity, rather than treating it may be the most viable solution ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(11)60815-5", "ISSN" : "1474-547X", "PMID" : "21872752", "abstract" : "The global obesity epidemic has been escalating for four decades, yet sustained prevention efforts have barely begun. An emerging science that uses quantitative models has provided key insights into the dynamics of this epidemic, and enabled researchers to combine evidence and to calculate the effect of behaviours, interventions, and policies at several levels--from individual to population. Forecasts suggest that high rates of obesity will affect future population health and economics. Energy gap models have quantified the association of changes in energy intake and expenditure with weight change, and have documented the effect of higher intake on obesity prevalence. Empirical evidence that shows interventions are effective is limited but expanding. We identify several cost-effective policies that governments should prioritise for implementation. Systems science provides a framework for organising the complexity of forces driving the obesity epidemic and has important implications for policy makers. Many parties (such as governments, international organisations, the private sector, and civil society) need to contribute complementary actions in a coordinated approach. Priority actions include policies to improve the food and built environments, cross-cutting actions (such as leadership, healthy public policies, and monitoring), and much greater funding for prevention programmes. Increased investment in population obesity monitoring would improve the accuracy of forecasts and evaluations. The integration of actions within existing systems into both health and non-health sectors (trade, agriculture, transport, urban planning, and development) can greatly increase the influence and sustainability of policies. We call for a sustained worldwide effort to monitor, prevent, and control obesity.", "author" : [ { "dropping-particle" : "", "family" : "Gortmaker", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swinburn", "given" : "Boyd A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carter", "given" : "Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mabry", "given" : "Patricia L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finegood", "given" : "Diane T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Terry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marsh", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moodie", "given" : "Marjory L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9793", "issued" : { "date-parts" : [ [ "2011", "8", "27" ] ] }, "page" : "838-847", "publisher" : "Elsevier Ltd", "title" : "Changing the future of obesity: science, policy, and action.", "type" : "article-journal", "volume" : "378" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gortmaker et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gortmaker et al. 2011). The moderate to high hereditability of obesity, estimated to be between 0.47 and 0.90 using twin studies and between 0.24 and 0.81 using family studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fendo.2012.00029", "ISSN" : "1664-2392", "PMID" : "22645519", "abstract" : "Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.", "author" : [ { "dropping-particle" : "", "family" : "Elks", "given" : "Cathy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "" } ], "container-title" : "Frontiers in Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "29", "title" : "Variability in the heritability of body mass index: a systematic review and meta-regression", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Elks et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Elks et al. 2012), the hereditability of eating characteristics such as energy consumption and dietary macronutrient distribution ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2013.05.039", "ISSN" : "1873-507X", "PMID" : "23748099", "abstract" : "BACKGROUND: Few twin studies have examined nutrition-related phenotypes among children, and none has investigated energy and macronutrient intakes. OBJECTIVE: The objective was to quantify genetic and environmental influences on variations in energy and macronutrient intakes among children aged 9 years. DESIGN: We conducted a nutrition study among children participating in the Quebec Newborn Twin Study, a population-based birth cohort of twins. We derived dietary data from two multiple-pass 24-hour dietary recalls with a parent and his or her child. The analysis employed a classic twin study design and used data from 379 twin pairs. RESULTS: Univariate analyses indicate that heritability for mean daily energy (kcal) and macronutrient (g) intakes was moderate, ranging from 0.34 (95% CI: 0.22, 0.46) to 0.42 (0.31, 0.53). Genetic effects also accounted for 0.28 (0.16, 0.40) of the variance in percent of energy from lipids, while only environmental (shared and unique) effects accounted for the variance in percent of energy from proteins and carbohydrates. The shared environment did not contribute to variations in daily intakes for most of the nutritional variables under study. Multivariate analyses suggest the presence of macronutrient-specific genetic influences for lipids and carbohydrates, estimated at 0.12 (0.04, 0.19) and 0.20 (0.11, 0.29) respectively. CONCLUSIONS: The unique environment (i.e., not shared by family members) has the largest influence on variances in daily energy and macronutrient intakes in 9-year-old children. This finding underscores the need to take obesogenic environments into account when planning dietary interventions for younger populations.", "author" : [ { "dropping-particle" : "", "family" : "Dubois", "given" : "Lise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diasparra", "given" : "Maikol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "B\u00e9dard", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontaine-Bisson", "given" : "B\u00e9n\u00e9dicte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P\u00e9russe", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tremblay", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boivin", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & Behavior", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "7", "2" ] ] }, "page" : "30-37", "publisher" : "Elsevier Inc.", "title" : "Gene-environment contributions to energy and macronutrient intakes in 9-year-old children: results from the Quebec Newborn Twin Study", "type" : "article-journal", "volume" : "119" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0002-9165", "PMID" : "15113724", "abstract" : "BACKGROUND: Uncompensated overnutrition promotes obesity, but the controls of children's eating behavior are poorly understood. Insights may be achieved by testing whether the eating patterns of children are associated with demographic variables or whether they aggregate among family members. OBJECTIVE: We tested whether children's total energy intake and macronutrient intake and their ability to compensate for earlier energy intake were associated with sociodemographic variables and anthropometric indexes. We also tested whether these behavioral traits aggregate among siblings. DESIGN: Thirty-two sibling pairs aged 3-7 y consumed a multi-item lunch preceded by a low-energy (12.55 kJ) or high-energy (627.60 kJ) preload drink. Mixed-models regression tested the associations between children's energy intake, demographic variables, and anthropometric measures. An intraclass correlation coefficient quantified the family correlation of the measures of children's eating. RESULTS: Children consumed significantly more total energy after consuming the low-energy preload ( +/- SD: 2237.39 +/- 1176.45 kJ) than after consuming the high-energy preload (1601.18 +/- 930.65 kJ). Compensation ability was unrelated to the children's age, sex, or ethnicity. Total energy and macronutrient intake, but not compensation propensity, were associated among siblings. CONCLUSIONS: The familial association of total energy and macronutrient intakes, independent of anthropometric measures, suggests genetic or home environmental influences specific to these behaviors. Short-term energy compensation, although very accurate within this sample, showed no significant familial correlation.", "author" : [ { "dropping-particle" : "", "family" : "Faith", "given" : "Myles S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keller", "given" : "Kathleen L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Susan L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietrobelli", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matz", "given" : "Patty E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Must", "given" : "Shoshanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jorge", "given" : "Marie Alexandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooperberg", "given" : "Jordana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heymsfield", "given" : "Steven B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2004", "5" ] ] }, "page" : "844-850", "title" : "Familial aggregation of energy intake in children", "type" : "article-journal", "volume" : "79" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3945/jn.108.087668.TABLE", "author" : [ { "dropping-particle" : "", "family" : "Hasselbalch", "given" : "Ann Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitmann", "given" : "Berit L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "Thorkild I A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Nutrition", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2406-2412", "title" : "Studies of twins indicate that genetics influence dietary intake", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "0031-9384", "PMID" : "9817574", "abstract" : "A sample of 66 monozyogtic twins reared apart (MZA) and 51 dizygotic twins reared apart (DZA), and 101 nontwin individuals (mostly spouses of the twins) who participated in the Minnesota Study of Twins Reared Apart (MISTRA) from 1979 to 1995 completed a self-report food frequency questionnaire. Intraclass-correlations and model-fitting analyses indicated that approximately 30% of the variance in the self-report of diet was attributable to genetic factors, with random environmental factors and measurement error responsible for the remaining variance. Spouse correlations were moderate. To investigate the effects of living together during marriage, the absolute differences between husband and wife on the dietary variables with years of marriage were correlated. None of the correlations were significant. Hierarchical multiple regression analyses also indicated that no convergence occurred during marriage. These results suggest that sharing a current family environment exerts minimal influence on individual differences in self-reported diet.", "author" : [ { "dropping-particle" : "", "family" : "Hur", "given" : "Y M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bouchard", "given" : "T J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eckert", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiology & Behavior", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "1998", "7" ] ] }, "page" : "629-636", "title" : "Genetic and environmental influences on self-reported diet: a reared-apart twin study", "type" : "article-journal", "volume" : "64" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/oby.2007.177", "ISSN" : "1930-7381", "PMID" : "17557986", "abstract" : "OBJECTIVE: Eating in the absence of hunger (EAH) may be a genetically influenced phenotype of overweight children, but evidence is limited. This research evaluated the heritability (h(2)) of EAH and its association with overweight among Hispanic children 5 to 18 years old. Genetic and environmental associations of EAH with overweight, fat mass, and key hormonal regulators of food intake were also evaluated. RESEARCH METHODS AND PROCEDURES: A family design was used to study 801 children from 300 Hispanic families. Weighed food intakes were used to measure EAH after an ad libitum dinner providing 50% of estimated energy needs. Fasting ghrelin, amylin, insulin, and leptin were measured by immunoassays. Measured heights, weights, and fat mass (using DXA) were obtained. Total energy expenditure (TEE) was measured by room respiration calorimetry. RESULTS: On average, children consumed 41% of TEE at the dinner meal, followed by an additional 19% of TEE in the absence of hunger. Overweight children consumed 6.5% more energy at dinner (p < 0.001) and 14% more energy in the absence of hunger (p < 0.001) than non-overweight children. Significant heritabilities were seen for EAH (h(2) = 0.51) and dinner intake (h(2) = 0.52) and for fasting levels of ghrelin (h(2) = 0.67), amylin (h(2) = 0.37), insulin (h(2) = 0.37), and leptin (h(2) = 0.34). Genetic correlations were seen between eating behavior and fasting hormones, suggesting common underlying genes affecting their expression. DISCUSSION: This research provides new evidence that overweight Hispanic children exhibit elevated levels of hyperphagic eating behaviors that are influenced by genetic endowment.", "author" : [ { "dropping-particle" : "", "family" : "Fisher", "given" : "Jennifer O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Guowen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaramillo", "given" : "Sandra J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cole", "given" : "Shelly a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Comuzzie", "given" : "Anthony G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butte", "given" : "Nancy F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-5", "issue" : "6", "issued" : { "date-parts" : [ [ "2007", "6" ] ] }, "page" : "1484-1495", "title" : "Heritability of hyperphagic eating behavior and appetite-related hormones among Hispanic children", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hur et al. 1998; Faith et al. 2004; Fisher et al. 2007; Hasselbalch et al. 2008; Dubois et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hur et al. 1998; Faith et al. 2004; Fisher et al. 2007; Hasselbalch et al. 2008; Dubois et al. 2013), and the identification of common variants located in or near approximately 70 loci that are associated with obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677921", "ISSN" : "1875-5488", "PMID" : "22043164", "abstract" : "Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of \"deep phenotyping\" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "154-168", "title" : "Molecular basis of obesity: current status and future prospects.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011b) suggest that understanding the underlying genetic architecture of obesity may be an important step in determining how to prevent obesity. Researchers are investigating ways in which genetics may be causing weight increase by testing the association of obesity predisposing SNPs with eating behaviours among other endophenotypes (e.g. energy expenditure). The strongest evidence currently involves total energy intake ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cecil", "given" : "Joanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavendale", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watt", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hetherington", "given" : "Marion M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "N Engl J Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2558-2566", "title" : "An obesity-associated FTO gene variant and increased energy intake in children", "type" : "article-journal", "volume" : "359" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1938-3207", "PMID" : "18842783", "abstract" : "BACKGROUND: A region of chromosome 16 containing the fat mass-and obesity-associated gene (FTO) is reproducibly associated with fat mass and body mass index (BMI), risk of obesity, and adiposity. OBJECTIVES: We aimed to assess the possibility that appetite plays a role in the association between FTO and BMI. DESIGN: Detailed dietary report information from the Avon Longitudinal Study of Parents and Children allowed the exploration of relations between FTO variation and dietary intake. Analyses were performed to investigate possible associations between variation at the FTO locus and the intake of a range of micronutrients and macronutrients, with adjustment for the bias often found within dietary report data when factors related to BMI are assessed. To test the hypothesis that FTO may be influencing appetite directly, rather than indirectly via BMI and altered intake requirements, we also assessed associations between FTO and dietary intake independent of BMI. RESULTS: Relations between a single-nucleotide polymorphism characterizing the FTO signal (rs9939609) and dietary variables were found and can be summarized by the effect of each additional allele (per-allele effects) on total energy and total fat (P < 0.001 for both). These associations were attenuated, but they persisted specifically for fat and energy consumption after adjustment for BMI [total daily fat consumption: approximately 1.5 g/d (P = 0.02 for the per-allele difference); total daily energy consumption: approximately 25 kJ/d (P = 0.03 for the per-allele difference)]. CONCLUSION: These associations suggest that persons carrying minor variants at rs9939609 were consuming more fat and total energy than were those not carrying such variants. They also suggest that this difference was not simply dependent on having higher average BMIs among the former group.", "author" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emmett", "given" : "Pauline 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" : "Rogers", "given" : "Imogen", "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" : "Davey Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "971-978", "title" : "The fat mass- and obesity-associated locus and dietary intake in children", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/oby.2008.318", "ISSN" : "1930-7381", "PMID" : "18551109", "abstract" : "The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the \"at risk\" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rance", "given" : "Kellie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnstone", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "1961-1965", "title" : "Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1055/s-0028-1087176", "ISSN" : "1439-3646", "PMID" : "19053021", "abstract" : "Polymorphisms in the FTO (fat mass- and obesity-associated) gene are associated with obesity. The mechanisms how genetic variation in this gene influences body weight are unknown. Body weight is determined by energy intake/storage and energy expenditure. In this study, we investigated whether genetic variation in FTO influences energy expenditure or food intake in carefully phenotyped subjects. In 380 German subjects, insulin sensitivity was measured by a hyperinsulinemic euglycemic clamp. Lean body mass and body fat were quantified using the bioimpedance method. Indirect calorimetry was used to estimate the metabolic rate. Food intake was assessed using food diaries (mean 11+/-1 d) in 151 subjects participating in a lifestyle intervention program to prevent diabetes. All subjects were genotyped for the FTO single nucleotide polymorphism (SNP) rs8050136. The risk allele of SNP rs8050136 was associated with higher body fat-related parameters (all p< or =0.04, additive inheritance model). Energy expenditure was not affected by the SNP. However, the risk allele of rs8050136 was significantly associated with higher energy intake (p=0.01, dominant inheritance model) during dietary restriction. Our data suggest that the increased body weight in carriers of the risk allele of FTO SNP rs8050136 is a consequence of increased food intake, but not of impaired energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Haupt", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thamer", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staiger", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tschritter", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirchhoff", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Machicao", "given" : "F", "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" : "Stefan", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fritsche", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Exp Clin Endocrinol Diabetes", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "194-197", "title" : "Variation in the FTO gene influences food intake but not energy expenditure", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cecil et al. 2008; Speakman et al. 2008; Timpson et al. 2008; Haupt et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cecil et al. 2008; Speakman et al. 2008; Timpson et al. 2008; Haupt et al. 2009), though some SNPs have also been found to be associated with macronutrient intakes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.2009.27781.INTRODUCTION", "author" : [ { "dropping-particle" : "", "family" : "Bauer", "given" : "Florianne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elbers", "given" : "Clara C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "Roger A H", "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" : "Onland-moret", "given" : "N Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Vliet-ostaptchouk", "given" : "Jana V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van Der", "family" : "Schouw", "given" : "Yvonne T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "951-959", "title" : "Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference 1 \u2013 3", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/aje/kwt028", "ISSN" : "1476-6256", "PMID" : "23820787", "abstract" : "Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (\u03b2meta = 0.2244 (standard error, 0.0548); P = 4 \u00d7 10(-5)) and inversely associated with percentage of calories derived from carbohydrate (\u03b2meta = -0.2796 (standard error, 0.0709); P = 8 \u00d7 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2), 95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.", "author" : [ { "dropping-particle" : "", "family" : "Park", "given" : "Sungshim Lani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheng", "given" : "Iona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pendergrass", "given" : "Sarah a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kucharska-Newton", "given" : "Anna M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Unhee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ambite", "given" : "Jose Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caberto", "given" : "Christian P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monroe", "given" : "Kristine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schumacher", "given" : "Fredrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hindorff", "given" : "Lucia a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oetjens", "given" : "Matthew T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goodloe", "given" : "Robert J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Love", "given" : "Shelly-Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henderson", "given" : "Brian E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kolonel", "given" : "Laurence N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haiman", "given" : "Christopher a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Dana C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heiss", "given" : "Gerardo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ritchie", "given" : "Marylyn D", "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" : "Lo\u00efc", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Epidemiol", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "9", "1" ] ] }, "page" : "780-790", "title" : "Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study", "type" : "article-journal", "volume" : "178" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3945/ajcn.112.052183", "ISSN" : "1938-3207", "PMID" : "23636237", "abstract" : "BACKGROUND: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. OBJECTIVE: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. DESIGN: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 \u00d7 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. RESULTS: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (\u03b2 \u00b1 SE: 0.25 \u00b1 0.04%; P = 1.68 \u00d7 10(-8)) and lower fat (\u03b2 \u00b1 SE: -0.21 \u00b1 0.04%; P = 1.57 \u00d7 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (\u03b2 \u00b1 SE: 0.10 \u00b1 0.02%; P = 9.96 \u00d7 10(-10)), independent of BMI (after adjustment for BMI, \u03b2 \u00b1 SE: 0.08 \u00b1 0.02%; P = 3.15 \u00d7 10(-7)). CONCLUSION: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ngwa", "given" : "Julius S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rooij", "given" : "Frank J a", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wojczynski", "given" : "Mary K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frazier-Wood", "given" : "Alexis C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Houston", "given" : "Denise K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemaitre", "given" : "Rozenn N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mikkil\u00e4", "given" : "Vera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renstrom", "given" : "Frida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chu", "given" : "Audrey Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira Otto", "given" : "Marcia C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhurandhar", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feitosa", "given" : "Mary F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Ingegerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohman", "given" : "Kurt K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manichaikul", "given" : "Ani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "Nicola M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mozaffarian", "given" : "Dariush", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viikari", "given" : "Jorma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Zheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandinelli", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yongmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyytik\u00e4inen", "given" : "Leo-Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitriou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "Goran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00e4h\u00f6nen", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ordovas", "given" : "Jose M", "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" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalafati", "given" : "Ioanna-Panagiota", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raitakari", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franco", "given" : "Oscar H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrack", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Semba", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnett", "given" : "Donna K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid 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" : "Kritchevsky", "given" : "Stephen B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtim\u00e4ki", "given" : "Terho", "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" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cupples", "given" : "L Adrienne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nettleton", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "1395-1402", "title" : "Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bauer et al. 2009; Park et al. 2013; Tanaka et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bauer et al. 2009; Park et al. 2013; Tanaka et al. 2013) or amount of food consumed from specific food groups ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mccaffery et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mccaffery et al. 2012). Studies have also shown associations between obesity predisposing SNPs and how people eat such as the number of eating episodes, the amount of disinhibition when eating, snacking habits, and satiety ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00109-013-1027-z", "ISBN" : "0010901310", "ISSN" : "1432-1440", "PMID" : "23640704", "abstract" : "We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (\u03b2 = 0.180 [0.022-0.339], P value = 0.0258 and \u03b2 = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (\u03b2 = 0.151 [-0.006 to 0.309], P value = 0.0591 and \u03b2 = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.", "author" : [ { "dropping-particle" : "", "family" : "Robiou-du-Pont", "given" : "S\u00e9bastien", "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" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "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" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Mol Med", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "5", "3" ] ] }, "title" : "Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/ijo.2008.279", "ISSN" : "1476-5497", "PMID" : "19153581", "abstract" : "Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P=0.01) and Swiss obese adults (P=0.04) as well as in adolescents from the Finnish general population (P=0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P=0.02) and in obese children with a higher prevalence of eating large amounts of food (P=0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-of-function mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.", "author" : [ { "dropping-particle" : "", "family" : "Stutzmann", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Calvacanti-Proen\u00e7a", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pigeyre", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "A-L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weill", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potoczna", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laitinen", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00e4rvelin", "given" : "M-R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Obes", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2009", "3" ] ] }, "page" : "373-378", "title" : "Common genetic variation near MC4R is associated with eating behaviour patterns in European populations", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1210/jc.2008-0472", "ISSN" : "0021-972X", "PMID" : "18583465", "abstract" : "CONTEXT: Polymorphisms within the FTO gene have consistently been associated with obesity across multiple populations. However, to date, it is not known whether the association between genetic variation in FTO and obesity is mediated through effects on energy intake or energy expenditure. OBJECTIVE: Our objective was to examine the association between alleles of FTO known to increase obesity risk and measures of habitual appetitive behavior. METHODS: The intronic FTO single nucleotide polymorphism (rs9939609) was genotyped in 3337 United Kingdom children in whom measures of habitual appetitive behavior had been assessed using two scales (Satiety Responsiveness and Enjoyment of Food) from the Child Eating Behaviour Questionnaire, a psychometric tool that has been validated against objective measures of food intake. Associations of FTO genotype with indices of adiposity and appetite were assessed by ANOVA. RESULTS: As expected, the A allele was associated with increased adiposity in this cohort and in an independent case-control replication study of United Kingdom children of similar age. AA homozygotes had significantly reduced Satiety Responsiveness scores (P = 0.008, ANOVA). Mediation analysis indicated that the association of the AA genotype with increased adiposity was explained in part through effects on Satiety Responsiveness. CONCLUSIONS: We have used a unique dataset to examine the relationship between a validated measure of children's habitual appetitive behavior and FTO obesity risk genotype and conclude that the commonest known risk allele for obesity is likely to exert at least some of its effects by influencing appetite.", "author" : [ { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carnell", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haworth", "given" : "Claire M a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Clin Endocrinol Metab", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2008", "9" ] ] }, "page" : "3640-3", "title" : "Obesity associated genetic variation in FTO is associated with diminished satiety", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wardle et al. 2008; Stutzmann et al. 2009; Mccaffery et al. 2012; Robiou-du-Pont et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wardle et al. 2008; Stutzmann et al. 2009; Mccaffery et al. 2012; Robiou-du-Pont et al. 2013). Though there is sufficient evidence to conclude that eating behaviours at least partially mediate the relationship between the obesity predisposing SNPs and measures of obesity, the limited access to genotypic and phenotypic data in large populations as well as small effect sizes require a further investigation of these relationships to confirm current findings as well as to look at other eating patterns. Eating disorders, including AN, BN, and BED are extreme eating patterns that are also worthy of investigation. They are heritable diseases with hereditability estimates of 0.28 to 0.78 for AN, 0.30 to 0.83 for BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1375/183242705774310114", "ISSN" : "1832-4274", "PMID" : "16212836", "abstract" : "Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "467-482", "title" : "Eating disorders: from twin studies to candidate genes and beyond", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Slof-Op \u2019t Landt et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Slof-Op ’t Landt et al. 2005), and 0.41 to 0.57 for BED ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/7854", "author" : [ { "dropping-particle" : "", "family" : "Thornton", "given" : "Laura M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mazzeo", "given" : "Suzanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Topics in Behavioral Neuroscience", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "141-156", "title" : "The heritability of eating disorders: Methods and current findings", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Thornton et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Thornton et al. 2011). Despite the moderate to high heritability of the diseases, there is little evidence supporting the role of functional mutations in genes that may be increasing risk for the eating disorders. Because eating disorders are heritable there is reason to believe that historically, characteristics of the diseases would have offered a competitive advantage for survival. Theorizing about potential evolutionary advantages of symptoms of eating disorders with the support of modern epidemiological evidence may help future gene identification efforts. With adequate sample sizes GWAS should be able to identify genes predisposing to eating disorders and the evolutionary theories may help provide strong biological evidence strengthening the findings of GWAS. Understanding the genetic architecture of eating disorders, particularly BN and BED which involve excessive food consumption, may help to identify new genes associated with obesity or disordered eating behaviours as well as determining biological pathways through which genes are regulating feeding behaviour.The objectives of this thesis are: To investigate the association of obesity predisposing SNPs and a gene score with nutrient consumption parameters including the intake of total energy, total fat, saturated fat, trans fat, monounsaturated fat, polyunsaturated fat, carbohydrates, and protein intake in a population of European ancestry.To look at eating disorders from an evolutionary perspective using current epidemiological evidence to help in future gene identification efforts for eating disorders.4.0 The Association of Obesity SNPs with Food Consumption Patterns 4.1 Introduction The rise of obesity in the past three decades has reached worldwide epidemic proportions ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(10)62037-5", "ISSN" : "1474-547X", "PMID" : "21295846", "abstract" : "Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI.", "author" : [ { "dropping-particle" : "", "family" : "Finucane", "given" : "Mariel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Gretchen A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowan", "given" : "Melanie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danaei", "given" : "Goodarz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "John K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paciorek", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Gitanjali M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutierrez", "given" : "Hialy R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bahalim", "given" : "Adil N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farzadfar", "given" : "Farshad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Leanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ezzati", "given" : "Majid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9765", "issued" : { "date-parts" : [ [ "2011", "2", "12" ] ] }, "page" : "557-567", "publisher" : "Elsevier Ltd", "title" : "National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9\u00b71 million participants.", "type" : "article-journal", "volume" : "377" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Finucane et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Finucane et al. 2011). Obesity is associated with numerous psychosocial and health-related complications including type 2 diabetes mellitus, gallbladder disease, osteoarthritis, coronary heart disease, some types of cancer, and decreased life expectancy ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Must", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spadano", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coakley", "given" : "E H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Field", "given" : "A E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colditz", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dietz", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Med Assoc", "id" : "ITEM-1", "issue" : "16", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "1523-1529", "title" : "The disease burden associated with overweight and obesity", "type" : "article-journal", "volume" : "282" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Calle", "given" : "Eugenia E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodriquez", "given" : "Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker-Thurmond", "given" : "Kimberly", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thun", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "New Engl J Med", "id" : "ITEM-2", "issue" : "17", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "1625-1638", "title" : "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults", "type" : "article-journal", "volume" : "348" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fontaine", "given" : "Kevin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Redden", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Chenxi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Westfall", "given" : "Andrew O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Med Assoc", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "187-193", "title" : "Years of life lost due to obesity", "type" : "article-journal", "volume" : "289" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Must et al. 1999; Calle et al. 2003; Fontaine et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Must et al. 1999; Calle et al. 2003; Fontaine et al. 2003). The treatment options offered to obese patients vary based on the degree of obesity and associated co-morbidities as well as the potential side effects of the therapeutic options. For those with moderate forms of obesity, lifestyle interventions including food restriction and increased energy expenditure through physical activity are recommended. As the degree of obesity increases or in the presence of co-morbidities, pharmacotherapy options which work to decrease appetite such as sibutramine or decrease fat absorption such as orlistat may be offered and for the most obese patients, surgical interventions may be considered ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2012-3115", "ISSN" : "1945-7197", "PMID" : "23443815", "abstract" : "Obesity is a disease that is defined as the accumulation of excessive amounts of body fat and is associated with increased risk of serious illness, disability, and death. In clinical practice, obesity is best assessed by calculating body mass index and measuring waist circumference. Treatment options are determined based on the body mass index, waist circumference, and adverse health consequences the patient is experiencing or is at an increased risk for facing in the future. Today, overweight and obesity impacts the majority of patients we treat in our clinical practices. Although endocrinologists are uniquely positioned to treat one of the major consequences of our current obesity epidemic, type 2 diabetes, we also need to be positioned and prepared to effectively treat one of its major causes-obesity. Type 2 diabetes and obesity are very much intertwined. Treatment of each disease affects the other. For these reasons, endocrinologists need to be experts in the treatment of obesity as well as diabetes. They should keep up with advances in obesity treatment including lifestyle, pharmaceutical, and surgical strategies. These strategies offer opportunities for improving the overall treatment for our obese patients today and will continue to improve and expand over the next decade.", "author" : [ { "dropping-particle" : "", "family" : "Wyatt", "given" : "Holly R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of clinical endocrinology and metabolism", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "4" ] ] }, "page" : "1299-306", "title" : "Update on treatment strategies for obesity.", "type" : "article-journal", "volume" : "98" }, "uris" : [ "", "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1111/j.1467-789X.2011.00981.x", "ISSN" : "1467-789X", "PMID" : "22288431", "abstract" : "The study aims to compare anti-obesity interventions in a single evidence synthesis framework. Electronic databases were searched for randomized controlled trials of orlistat, rimonabant or sibutramine reporting weight or body mass index (BMI) change from baseline at 3, 6 or 12 months. A mixed treatment comparison was used to combine direct and indirect trial evidence. Ninety-four studies involving 24,808 individuals were included; 83 trials included data on weight change and 41 on BMI change. All results are in comparison with placebo. The active drugs were all effective at reducing weight and BMI. At 3 months, orlistat reduced weight by -2.65 kg (95% credibility interval -4.00 kg, -1.31 kg). For sibutramine, 15 mg gave a greater reduction than 10 mg at 12 months, -6.35 kg versus -5.42 kg, respectively. Rimonabant reduced weight by -11.23 kg at 3 months and -4.55 kg at 12 months. Lifestyle advice alone also reduced weight at 6 and 12 months, but was less effective than the pharmacological interventions. In conclusion, modest weight reductions were seen for all pharmacological interventions. Those interventions which have now been withdrawn from use (sibutramine and rimonabant) seem to be the most effective, implying that there may be a place in clinical practice for similar drugs if side effects could be avoided.", "author" : [ { "dropping-particle" : "", "family" : "Gray", "given" : "L J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dunkley", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warren", "given" : "F C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ara", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abrams", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davies", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khunti", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sutton", "given" : "a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity reviews : an official journal of the International Association for the Study of Obesity", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2012", "6" ] ] }, "page" : "483-98", "title" : "A systematic review and mixed treatment comparison of pharmacological interventions for the treatment of obesity.", "type" : "article-journal", "volume" : "13" }, "uris" : [ "", "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gray et al. 2012; Wyatt 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gray et al. 2012; Wyatt 2013). Though pharmacotherapy options have yielded successful results, they are associated with complications such as gastrointestinal problems with orlistat or cardiovascular risk with sibutramine ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gray", "given" : "Juliette", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yeo", "given" : "Giles S H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cox", "given" : "James J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morton", "given" : "Jenny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adlam", "given" : "Anna-lynne R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keogh", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanovski", "given" : "Jack A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "El", "family" : "Gharbawy", "given" : "Areeg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Joan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tung", "given" : "Y C Loraine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hodges", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raymond", "given" : "F Lucy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rahilly", "given" : "Stephen O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "3366-3371", "title" : "Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gray et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gray et al. 2008). Bariatric surgery is associated with significant weight loss ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ncpendmet0563", "ISSN" : "1745-8374", "PMID" : "17643128", "abstract" : "Obesity is very prevalent. Most treatments fail owing to hard-wired survival mechanisms, linking stress and appetite, which have become grossly maladaptive in the industrial era. Antiobesity (bariatric) surgery is a seemingly drastic, efficacious therapy for this serious disease of energy surfeit. Technical progress during the last two decades has greatly improved its safety. The surgical principles of gastric restriction and/or gastrointestinal diversion have remained largely unchanged over 40 years, although mechanisms of action have been elucidated concomitant with advances in knowledge of the molecular biology of energy balance and appetite regulation. Results of bariatric surgery in large case-series followed for at least 10 years consistently demonstrate amelioration of components of the insulin-resistance metabolic syndrome and other comorbidities, significantly improving quality of life. Furthermore, bariatric surgery has convincingly been demonstrated to reduce mortality compared with nonoperative methods. This surgery requires substantial preoperative and postoperative evaluation, teaching, and monitoring to optimize outcomes. In the absence of effective societal changes to restore a healthy energy balance, bariatric surgery is an important tool for treating a very serious disease.", "author" : [ { "dropping-particle" : "", "family" : "Kral", "given" : "John G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "N\u00e4slund", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature clinical practice. Endocrinology & metabolism", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8" ] ] }, "page" : "574-83", "title" : "Surgical treatment of obesity.", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kral and N\u00e4slund 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kral and N?slund 2007). However the most effective techniques involve rerouting the digestive tract. This can lead to malabsorption which can cause nutritional deficiencies if an adequate diet and supplementation regime is not maintained as well as post-operative complications including hemorrhage, staple-line dehiscence, thromboembolism, and death ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3238/arztebl.2011.0341", "ISSN" : "1866-0452", "PMID" : "21655459", "abstract" : "BACKGROUND: Bariatric surgery has increased in numbers, but the treatment of morbid obesity in Germany still needs improvement. The new interdisciplinary S3-guideline provides information on the appropriate indications, procedures, techniques, and follow-up care.\n\nMETHODS: Systematic review of the literature, classification of the evidence, graded recommendations, and interdisciplinary consensus-building.\n\nRESULTS: Bariatric surgery is a component of the multimodal treatment of obesity, which consists of multidisciplinary evaluation and diagnosis, conservative and surgical treatments, and lifelong follow-up care. The current guideline extends the BMI-based spectrum of indications that was previously proposed (BMI greater than 40 kg/m(2), or greater than 35 kg/m(2)with secondary diseases) by eliminating age limits, as well as most of the contraindications. A prerequisite for surgery is that a structured, conservative weight-loss program has failed or is considered to be futile. Type 2 diabetes is now considered an independent indication under clinical study conditions for patients whose BMI is less than 35 kg/m(2) (metabolic surgery). The standard laparoscopic techniques are gastric banding, gastric bypass, sleeve gastrectomy, and biliopancreatic diversion. The choice of procedure is based on knowledge of the results, long-term effects, complications, and individual circumstances. Structured lifelong follow-up should be provided and should, in particular, prevent metabolic deficiencies.\n\nCONCLUSION: The guideline contains recommendations based on the scientific evidence and on a consensus of experts from multiple disciplines about the indications for bariatric surgery, the choice of procedure, techniques, and follow-up care. It should be broadly implemented to improve patient care in this field.", "author" : [ { "dropping-particle" : "", "family" : "Runkel", "given" : "Norbert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colombo-Benkmann", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "H\u00fcttl", "given" : "Thomas P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tigges", "given" : "Harald", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mann", "given" : "Oliver", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sauerland", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Deutsches \u00c4rzteblatt international", "id" : "ITEM-1", "issue" : "20", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "341-6", "title" : "Bariatric surgery.", "type" : "article-journal", "volume" : "108" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Runkel et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Runkel et al. 2011). Despite the availability of diverse treatment options, there is evidence of only a modest effect of lifestyle interventions and pharmacotherapy and surgical options are associated with numerous complications, suggesting that preventing opposed to treating obesity may be the best strategy for curbing the obesity epidemic ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/S0140-6736(11)60815-5", "ISSN" : "1474-547X", "PMID" : "21872752", "abstract" : "The global obesity epidemic has been escalating for four decades, yet sustained prevention efforts have barely begun. An emerging science that uses quantitative models has provided key insights into the dynamics of this epidemic, and enabled researchers to combine evidence and to calculate the effect of behaviours, interventions, and policies at several levels--from individual to population. Forecasts suggest that high rates of obesity will affect future population health and economics. Energy gap models have quantified the association of changes in energy intake and expenditure with weight change, and have documented the effect of higher intake on obesity prevalence. Empirical evidence that shows interventions are effective is limited but expanding. We identify several cost-effective policies that governments should prioritise for implementation. Systems science provides a framework for organising the complexity of forces driving the obesity epidemic and has important implications for policy makers. Many parties (such as governments, international organisations, the private sector, and civil society) need to contribute complementary actions in a coordinated approach. Priority actions include policies to improve the food and built environments, cross-cutting actions (such as leadership, healthy public policies, and monitoring), and much greater funding for prevention programmes. Increased investment in population obesity monitoring would improve the accuracy of forecasts and evaluations. The integration of actions within existing systems into both health and non-health sectors (trade, agriculture, transport, urban planning, and development) can greatly increase the influence and sustainability of policies. We call for a sustained worldwide effort to monitor, prevent, and control obesity.", "author" : [ { "dropping-particle" : "", "family" : "Gortmaker", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swinburn", "given" : "Boyd A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carter", "given" : "Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mabry", "given" : "Patricia L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finegood", "given" : "Diane T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huang", "given" : "Terry", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marsh", "given" : "Tim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moodie", "given" : "Marjory L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-1", "issue" : "9793", "issued" : { "date-parts" : [ [ "2011", "8", "27" ] ] }, "page" : "838-847", "publisher" : "Elsevier Ltd", "title" : "Changing the future of obesity: science, policy, and action.", "type" : "article-journal", "volume" : "378" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gortmaker et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gortmaker et al. 2011).An excessive consumption of calories is the main risk factor for obesity with environmental and societal factors encouraging calorie consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0090-0036", "PMID" : "11818300", "abstract" : "OBJECTIVES: Because larger food portions could be contributing to the increasing prevalence of overweight and obesity, this study was designed to weigh samples of marketplace foods, identify historical changes in the sizes of those foods, and compare current portions with federal standards.\n\nMETHODS: We obtained information about current portions from manufacturers or from direct weighing; we obtained information about past portions from manufacturers or contemporary publications.\n\nRESULTS: Marketplace food portions have increased in size and now exceed federal standards. Portion sizes began to grow in the 1970s, rose sharply in the 1980s, and have continued in parallel with increasing body weights.\n\nCONCLUSIONS: Because energy content increases with portion size, educational and other public health efforts to address obesity should focus on the need for people to consume smaller portions.", "author" : [ { "dropping-particle" : "", "family" : "Young", "given" : "Lisa R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nestle", "given" : "Marion", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of public health", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "3" ] ] }, "page" : "246-9", "title" : "The contribution of expanding portion sizes to the US obesity epidemic.", "type" : "article-journal", "volume" : "92" }, "uris" : [ "", "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Young and Nestle 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Young and Nestle 2002). The current “obesogenic” environment is characterized by calorically dense food being inexpensive, abundant, served in large portions ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0090-0036", "PMID" : "11818300", "abstract" : "OBJECTIVES: Because larger food portions could be contributing to the increasing prevalence of overweight and obesity, this study was designed to weigh samples of marketplace foods, identify historical changes in the sizes of those foods, and compare current portions with federal standards.\n\nMETHODS: We obtained information about current portions from manufacturers or from direct weighing; we obtained information about past portions from manufacturers or contemporary publications.\n\nRESULTS: Marketplace food portions have increased in size and now exceed federal standards. Portion sizes began to grow in the 1970s, rose sharply in the 1980s, and have continued in parallel with increasing body weights.\n\nCONCLUSIONS: Because energy content increases with portion size, educational and other public health efforts to address obesity should focus on the need for people to consume smaller portions.", "author" : [ { "dropping-particle" : "", "family" : "Young", "given" : "Lisa R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nestle", "given" : "Marion", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of public health", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "3" ] ] }, "page" : "246-9", "title" : "The contribution of expanding portion sizes to the US obesity epidemic.", "type" : "article-journal", "volume" : "92" }, "uris" : [ "", "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Young and Nestle 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Young and Nestle 2002), and heavily marketed while demands for physical activity decrease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.psc.2011.08.005", "ISSN" : "1558-3147", "PMID" : "22098799", "abstract" : "The obesity epidemic in the United States has proven difficult to reverse. We have not been successful in helping people sustain the eating and physical activity patterns that are needed to maintain a healthy body weight. There is growing recognition that we will not be able to sustain healthy lifestyles until we are able to address the environment and culture that currently support unhealthy lifestyles. Addressing obesity requires an understanding of energy balance. From an energy balance approach it should be easier to prevent obesity than to reverse it. Further, from an energy balance point of view, it may not be possible to solve the problem by focusing on food alone. Currently, energy requirements of much of the population may be below the level of energy intake than can reasonably be maintained over time. Many initiatives are underway to revise how we build our communities, the ways we produce and market our foods, and the ways we inadvertently promote sedentary behavior. Efforts are underway to prevent obesity in schools, worksites, and communities. It is probably too early to evaluate these efforts, but there have been no large-scale successes in preventing obesity to date. There is reason to be optimistic about dealing with obesity. We have successfully addressed many previous threats to public health. It was probably inconceivable in the 1950s to think that major public health initiatives could have such a dramatic effect on reducing the prevalence of smoking in the United States. Yet, this serious problem was addressed via a combination of strategies involving public health, economics, political advocacy, behavioral change, and environmental change. Similarly, Americans have been persuaded to use seat belts and recycle, addressing two other challenges to public health. But, there is also reason to be pessimistic. Certainly, we can learn from our previous efforts for social change, but we must realize that our challenge with obesity may be greater. In the other examples cited, we had clear goals in mind. Our goals were to stop smoking, increase the use of seatbelts, and increase recycling. The difficulty of achieving these goals should not be minimized, but they were clear and simple goals. In the case of obesity, there is no clear agreement about goals. Moreover, experts do not agree on which strategies should be implemented on a widespread basis to achieve the behavioral changes in the population needed to reverse the high prevalence rates o\u2026", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Nia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Catenacci", "given" : "Victoria a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wyatt", "given" : "Holly R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "James O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Psychiatric Clinics of North America", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "717-732", "publisher" : "Elsevier Inc.", "title" : "Obesity: overview of an epidemic", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/S0140-6736(11)60813-1", "ISSN" : "1474-547X", "PMID" : "21872749", "abstract" : "The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers.", "author" : [ { "dropping-particle" : "", "family" : "Swinburn", "given" : "Boyd a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sacks", "given" : "Gary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Kevin D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Klim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finegood", "given" : "Diane T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moodie", "given" : "Marjory L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gortmaker", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-2", "issue" : "9793", "issued" : { "date-parts" : [ [ "2011", "8", "27" ] ] }, "page" : "804-814", "publisher" : "Elsevier Ltd", "title" : "The global obesity pandemic: shaped by global drivers and local environments", "type" : "article-journal", "volume" : "378" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mitchell et al. 2011; Swinburn et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mitchell et al. 2011; Swinburn et al. 2011). Though the environment is an important contributor to obesity, the inter-individual differences in obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fendo.2012.00029", "ISSN" : "1664-2392", "PMID" : "22645519", "abstract" : "Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.", "author" : [ { "dropping-particle" : "", "family" : "Elks", "given" : "Cathy E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoed", "given" : "Marcel", "non-dropping-particle" : "den", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sharp", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "" } ], "container-title" : "Frontiers in Endocrinology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012", "1" ] ] }, "page" : "29", "title" : "Variability in the heritability of body mass index: a systematic review and meta-regression", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Elks et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Elks et al. 2012) and food behaviors such as energy consumption, macronutrient consumption distribution, food preferences, and satiety responsiveness in the presence of the obesogenic environment can in part be explained by genetic factors ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.physbeh.2006.04.016", "ISSN" : "0031-9384", "PMID" : "16750228", "abstract" : "BACKGROUND: There is persisting interest in the idea that taste preferences are heritable characteristics, but few twin studies have found evidence for a significant genetic component. Small sample sizes and idiosyncratic selection of foods may have contributed to the negative results. We hypothesized that using a larger twin sample and empirical groupings of food types, would give stronger evidence for the heritability of food preferences. OBJECTIVE: We examined the heritability of preferences for four food groups in a sample of young twins. DESIGN: We administered a food preference questionnaire with 95 foods to 214 mothers of same-sex twin pairs (103 monozygotic and 111 dizygotic pairs) aged 4 to 5. 18 foods were excluded because they had been tried by fewer than 25% of the children. Foods were grouped into 'Vegetables', 'Fruits', 'Desserts' and 'Meat and Fish' on the basis of a factor analysis of the preference data. Genetic analyses were carried out on mean liking across these four groups, using model fitting techniques. RESULTS: Over all 77 foods, MZ correlations were higher than DZ correlations for 72 of them, with a higher mean MZ correlation (r = 0.76) than DZ correlation (r = 0.56). Using model fitting techniques with the factor scores, significant heritability estimates were obtained for all four food groups. Heritability was modest for dessert foods (0.20), moderate for vegetables (0.37) and fruits (0.51), and high for liking for protein foods (0.78). Shared environmental effects were strong for desserts, fruits and vegetables, while non-shared environmental influences were low for all four food groups. CONCLUSIONS: These results provide strong evidence for modest heritability of food preferences when using empirically-derived groupings of foods.", "author" : [ { "dropping-particle" : "", "family" : "Breen", "given" : "Fiona M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Physiol Behav", "id" : "ITEM-1", "issue" : "4-5", "issued" : { "date-parts" : [ [ "2006", "7", "30" ] ] }, "page" : "443-447", "title" : "Heritability of food preferences in young children.", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/oby.20592", "ISSN" : "1930-739X", "PMID" : "23929626", "abstract" : "OBJECTIVE: Many confirmed genetic loci for obesity are expressed in regions of the brain that regulate energy intake and reward-seeking behavior. Whether these loci contribute to the development of specific eating behaviors has not been investigated. The relationship between a genetic susceptibility to obesity and cognitive restraint, uncontrolled and emotional eating was examined. METHODS: Eating behavior and body mass index (BMI) were determined by questionnaires for 1471 men and 2381 women from two US cohorts. Genotypes were extracted from genome-wide scans and a genetic-risk score (GRS) derived from 32 obesity-loci was calculated. RESULTS: The GRS was positively associated with emotional and uncontrolled eating (P<0.002). In exploratory analysis, BMI-increasing variants of MTCH2, TNNI3K, and ZC3H4 were positively associated with emotional eating and those of TNNI3K and ZC3H4 were positively associated with uncontrolled eating. The BMI-increasing variant of FTO was positively and those of LRP1B and TFAP2B were inversely associated with cognitive restraint. These associations for single SNPs were independent of BMI but were not significant after multiple-testing correction. CONCLUSIONS: An overall genetic susceptibility to obesity may also extend to eating behaviors. The link between specific loci and obesity may be mediated by eating behavior but larger studies are warranted to confirm these results.", "author" : [ { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimm", "given" : "Eric B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curhan", "given" : "Gary C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "135-141", "title" : "Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3945/jn.108.087668.TABLE", "author" : [ { "dropping-particle" : "", "family" : "Hasselbalch", "given" : "Ann Louise", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heitmann", "given" : "Berit L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kyvik", "given" : "Kirsten O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "Thorkild I A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Nutrition", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2406-2412", "title" : "Studies of twins indicate that genetics influence dietary intake", "type" : "article-journal", "volume" : "138" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.3945/ajcn.111.023671.Am", "author" : [ { "dropping-particle" : "", "family" : "Llewellyn", "given" : "Clare H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Jaarsveld", "given" : "Cornelia H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Abigail", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Inherited behavioral susceptibility to adiposity in infancy : a multivariate genetic analysis of appetite and weight in the Gemini birth cohort 1 \u2013 3", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Breen et al. 2006; Hasselbalch et al. 2008; Llewellyn et al. 2012; Cornelis et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Breen et al. 2006; Hasselbalch et al. 2008; Llewellyn et al. 2012; Cornelis et al. 2014). In addition, heritability studies in twins evidenced a shared genetic component between obesity and food behaviors ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1938-3207", "PMID" : "18689360", "abstract" : "BACKGROUND: The relation between body weight and energy-dense foods remains unclear. OBJECTIVE: We estimated the effects of genetic and environmental factors on cognitive and emotional aspects of dieting behavior, body mass index (BMI), and responses to fatty foods and on their relations. DESIGN: A total of 1326 adult twin persons (aged 17-82 y; 17% M and 83% F) from the United Kingdom and Finland completed the revised version of the Three-Factor Eating Questionnaire (TFEQ-R18) and reported the liking and use-frequency of 4 sweet-and-fatty and salty-and-fatty food items (6 items in the United Kingdom and 5 items in Finland). Genetic modeling was done by using linear structural equations. RESULTS: Heritability estimates were calculated separately for the countries and sexes; they were 26-63% for cognitive restraint, 45-69% for uncontrolled eating, and 9-45% for emotional eating, respectively. Of the variation in liking and use-frequency of fatty foods, 24-54% was attributed to interindividual genetic differences. No significant correlations were observed between BMI and fatty food use or liking. However, BMI was positively (mostly genetically) correlated (genetic r = 0.16-0.51) with all of the dieting behaviors, and they correlated with fatty food use and liking ratings. Uncontrolled eating was both genetically and environmentally associated with liking for salty-and-fatty foods (genetic and environmental r = 0.16), and emotional eating was genetically associated with liking for sweet-and-fatty foods (genetic r = 0.31). CONCLUSIONS: The relation between BMI and diet appears to be mediated through dieting behaviors. Dietary counseling should focus on unhealthy dieting behaviors rather than only on direct advice on food use.", "author" : [ { "dropping-particle" : "", "family" : "Keskitalo", "given" : "Kaisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuorila", "given" : "Hely", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Tim D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cherkas", "given" : "Lynn F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knaapila", "given" : "Antti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silventoinen", "given" : "Karri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Perola", "given" : "Markus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "263-271", "title" : "The Three-Factor Eating Questionnaire, body mass index, and responses to sweet and salty fatty foods: a twin study of genetic and environmental associations", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3945/ajcn.111.023671.Am", "author" : [ { "dropping-particle" : "", "family" : "Llewellyn", "given" : "Clare H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Jaarsveld", "given" : "Cornelia H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Abigail", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Inherited behavioral susceptibility to adiposity in infancy : a multivariate genetic analysis of appetite and weight in the Gemini birth cohort 1 \u2013 3", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keskitalo et al. 2008b; Llewellyn et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keskitalo et al. 2008b; Llewellyn et al. 2012). This suggests that the genetic architecture of food behaviors and obesity may be at least partially overlapping.Monogenic forms of obesity include both syndromic types in which obesity occurs in conjunction with other symptoms and non-syndromic types in which obesity is the main clinical feature. Both types of monogenic obesity are characterized by severe hyperphagia ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677921", "ISSN" : "1875-5488", "PMID" : "22043164", "abstract" : "Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of \"deep phenotyping\" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Curr Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "154-168", "title" : "Molecular basis of obesity: current status and future prospects.", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011b)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011b). GWAS and candidate gene studies have identified close to 70 loci associated with obesity-related traits, nine of which (BDNF, NTRK2, LEPR, SH2B1, PCSK1, POMC, MC4R, TUB, SDCCAG8) overlap with monogenic forms of syndromic and non-snydromic obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677895", "ISSN" : "1875-5488", "PMID" : "22043165", "abstract" : "Candidate gene and genome-wide association studies have led to the discovery of nine loci involved in Mendelian forms of obesity and 58 loci contributing to polygenic obesity. These loci explain a small fraction of the heritability for obesity and many genes remain to be discovered. However, efforts in obesity gene identification greatly modified our understanding of this disorder. In this review, we propose an overlook of major lessons learned from 15 years of research in the field of genetics and obesity. We comment on the existence of the genetic continuum between monogenic and polygenic forms of obesity that pinpoints the role of genes involved in the central regulation of food intake and genetic predisposition to obesity. We explain how the identification of novel obesity predisposing genes has clarified unsuspected biological pathways involved in the control of energy balance that have helped to understand past human history and to explore causality in epidemiology. We provide evidence that obesity predisposing genes interact with the environment and influence the response to treatment relevant to disease prediction.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "169-179", "title" : "Genetics of obesity: What have we Learned?", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ng.274", "ISSN" : "1546-1718", "PMID" : "19079260", "abstract" : "Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.", "author" : [ { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudbjartsson", "given" : "Daniel F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sulem", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Helgadottir", "given" : "Anna", "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" : "Thorlacius", "given" : "Steinunn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsdottir", "given" : "Ingileif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsdottir", "given" : "Thorbjorg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olafsdottir", "given" : "Elinborg J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olafsdottir", "given" : "Gudridur H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Thorvaldur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Frosti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jorgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aben", "given" : "Katja K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verbeek", "given" : "Andr\u00e9 L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roeleveld", "given" : "Nel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kampman", "given" : "Ellen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanek", "given" : "Lisa R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Lewis C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tryggvadottir", "given" : "Laufey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rafnar", "given" : "Thorunn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Diane M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gulcher", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiemeney", "given" : "Lambertus a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "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" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "page" : "18-24", "title" : "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Thorleifsson et al. 2009; Choquet and Meyre 2011a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Thorleifsson et al. 2009; Choquet and Meyre 2011a). To date, only a limited number of obesity-predisposing SNPs (FTO, MC4R, BDNF, SH2B1, NEGR1, MTCH2) have been reliably associated with food-related traits ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.2009.27781.INTRODUCTION", "author" : [ { "dropping-particle" : "", "family" : "Bauer", "given" : "Florianne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elbers", "given" : "Clara C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Adan", "given" : "Roger A H", "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" : "Onland-moret", "given" : "N Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Vliet-ostaptchouk", "given" : "Jana V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijmenga", "given" : "Cisca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van Der", "family" : "Schouw", "given" : "Yvonne T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "951-959", "title" : "Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference 1 \u2013 3", "type" : "article-journal", "volume" : "90" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cecil", "given" : "Joanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavendale", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watt", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hetherington", "given" : "Marion M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "N Engl J Med", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2558-2566", "title" : "An obesity-associated FTO gene variant and increased energy intake in children", "type" : "article-journal", "volume" : "359" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1007/s00109-013-1027-z", "ISBN" : "0010901310", "ISSN" : "1432-1440", "PMID" : "23640704", "abstract" : "We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (\u03b2 = 0.180 [0.022-0.339], P value = 0.0258 and \u03b2 = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (\u03b2 = 0.151 [-0.006 to 0.309], P value = 0.0591 and \u03b2 = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.", "author" : [ { "dropping-particle" : "", "family" : "Robiou-du-Pont", "given" : "S\u00e9bastien", "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" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "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" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Mol Med", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2013", "5", "3" ] ] }, "title" : "Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1038/ijo.2010.219", "ISSN" : "1476-5497", "PMID" : "20975729", "abstract" : "We examined the association between the FTO rs9939609 polymorphism and serum leptin concentrations in adolescents. The FTO rs9939609 polymorphism was genotyped, and fasting serum leptin and insulin were measured in 655 European adolescents (365 females) aged 14.6 \u00b1 1.2 years. We measured weight, height, triceps and subscapular skinfolds and waist circumference, and body fat percentage was calculated. Sex, pubertal status, center, physical activity (accelerometry), total or central adiposity and serum insulin concentrations were entered as confounders in the analyses. The minor A allele of the FTO rs9939609 was significantly associated with higher serum leptin concentrations independently of potential confounders including adiposity (+3.9 ng ml(-1) per risk allele (95% confidence interval: 2.0, 5.9); adjusted P < 0.001). These findings could link the FTO gene with serum leptin and consequently with the control of energy balance. Leptin could be a possible intermediary contributing to the association between the FTO rs9939609 polymorphism and adiposity.", "author" : [ { "dropping-particle" : "", "family" : "Stutzmann", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pigeyre", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "A-l", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheehy", "given" : "Ann M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaddis", "given" : "Nathan C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "Jonathan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malim", "given" : "Michael H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Lappalainen", "given" : "Tiina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindstr\u00f6m", "given" : "Jaana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paananen", "given" : "Jussi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karhunen", "given" : "Leila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tuomilehto", "given" : "Jaakko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uusitupa", "given" : "Matti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ren", "given" : "Decheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhou", "given" : "Yingjiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morris", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Minghua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Zhiqin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rui", "given" : "Liangyou", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Labayen", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruiz", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ortega", "given" : "F B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dallongeville", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dalongeville", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jim\u00e9nez-Pav\u00f3n", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castillo", "given" : "M J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henauw", "given" : "S", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonz\u00e1lez-Gross", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bueno", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Molnar", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kafatos", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "D\u00edaz", "given" : "L E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meirhaeghe", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreno", "given" : "L a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "M\u00fcnzberg", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bj\u00f6rnholm", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bates", "given" : "S H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Myers", "given" : "M G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nassir", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kosoy", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Garcia", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ochs-Balcom", "given" : "H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tylavsky", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manson", "given" : "J E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shigeta", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robbins", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seldin", "given" : "M F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wardle", "given" : "Jane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carnell", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haworth", "given" : "Claire Ma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plomin", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McAllister", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "V", "family" : "Dhurandhar", "given" : "Nikhil", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keith", "given" : "Scott W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aronne", "given" : "Louis J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barger", "given" : "Jamie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baskin", "given" : "Monica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benca", "given" : "Ruth M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biggio", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boggiano", "given" : "Mary M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eisenmann", "given" : "Joe C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elobeid", "given" : "Mai", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fontaine", "given" : "Kevin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gluckman", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hanlon", "given" : "Erin C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katzmarzyk", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pietrobelli", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Redden", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruden", "given" : "Douglas M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wang", "given" : "Chenxi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waterland", "given" : "Robert a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wright", "given" : "Suzanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Allison", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wee", "given" : "Christina C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Phillips", "given" : "Russell S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Legedza", "given" : "Anna T R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Davis", "given" : "Roger B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soukup", "given" : "Jane R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colditz", "given" : "Graham a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hamel", "given" : "Mary Beth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lq", "given" : "Hfolqh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shfwdqf", "given" : "L I H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wkh", "given" : "L Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huvkrz", "given" : "Xwkru Rxjodv", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Do", "given" : "D G H Q H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ixoo", "given" : "Lqnv", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dqg", "given" : "W H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vhuylfhv", "given" : "Uhodwhg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dqg", "given" : "Rehvlw", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iurp", "given" : "Pruwdolw", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lq", "given" : "Fdqfhu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vwxglhg", "given" : "D Survshfwlyho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ri", "given" : "Frkruw", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xjhqld", "given" : "Dooh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lpehuo", "given" : "Duphq Donhu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olqn", "given" : "Grfxphqw", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lqioxhqfh", "given" : "Evwudfw", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fhvv", "given" : "R I H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhljkw", "given" : "E R G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wkh", "given" : "R Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ri", "given" : "Ulvn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iurp", "given" : "Ghdwk", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kdv", "given" : "Fdqfhu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ehhq", "given" : "Q R W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fkdudfwhul", "given" : "Ixoo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iuhh", "given" : "Zhuh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fdqfhu", "given" : "R I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hquroophqw", "given" : "D W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wkhuh", "given" : "L Q", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghdwkv", "given" : "Zhuh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fdqfhu", "given" : "Iurp", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hduv", "given" : "Gxulqj", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Iroorz", "given" : "R I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Must", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spadano", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coakley", "given" : "EH", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Field", "given" : "AE", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "WH", "given" : "Dietz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finucane", "given" : "Mariel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Gretchen a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cowan", "given" : "Melanie J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Danaei", "given" : "Goodarz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lin", "given" : "John K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paciorek", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Gitanjali M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gutierrez", "given" : "Hialy R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lu", "given" : "Yuan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bahalim", "given" : "Adil N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farzadfar", "given" : "Farshad", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riley", "given" : "Leanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ezzati", "given" : "Majid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-5", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1", "12" ] ] }, "page" : "1523-1529", "publisher" : "Elsevier Ltd", "title" : "The disease burden associated with overweight and obesity", "type" : "article-journal", "volume" : "282" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1007/s12263-013-0352-8", "ISSN" : "1555-8932", "PMID" : "23861046", "abstract" : "Gene-environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malm\u00f6 Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 \u00d7 10(-34)), fat mass (P = 6.3 \u00d7 10(-28)) and fat-free mass (P = 1.3 \u00d7 10(-24)). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 \u00d7 10(-4)). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet.", "author" : [ { "dropping-particle" : "", "family" : "Rukh", "given" : "Gull", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedblad", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wirf\u00e4lt", "given" : "Elisabet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ericson", "given" : "Ulrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genes & Nutrition", "id" : "ITEM-6", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "7", "17" ] ] }, "page" : "535-547", "title" : "Genetic susceptibility to obesity and diet intakes: association and interaction analyses in the Malm\u00f6 Diet and Cancer Study", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cecil et al. 2008; Bauer et al. 2009; Stutzmann et al. 2011; Mccaffery et al. 2012; Robiou-du-Pont et al. 2013; Rukh et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cecil et al. 2008; Bauer et al. 2009; Stutzmann et al. 2011; Mccaffery et al. 2012; Robiou-du-Pont et al. 2013; Rukh et al. 2013).Though an obesity genotype score consisting of 13 risk alleles was associated with higher body mass index (BMI), it was unexpectedly associated with lower total energy intake and higher intake of fiber in 26,107 Northern European subjects, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12263-013-0352-8", "ISSN" : "1555-8932", "PMID" : "23861046", "abstract" : "Gene-environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malm\u00f6 Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 \u00d7 10(-34)), fat mass (P = 6.3 \u00d7 10(-28)) and fat-free mass (P = 1.3 \u00d7 10(-24)). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 \u00d7 10(-4)). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet.", "author" : [ { "dropping-particle" : "", "family" : "Rukh", "given" : "Gull", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedblad", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wirf\u00e4lt", "given" : "Elisabet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ericson", "given" : "Ulrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genes & Nutrition", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "7", "17" ] ] }, "page" : "535-547", "title" : "Genetic susceptibility to obesity and diet intakes: association and interaction analyses in the Malm\u00f6 Diet and Cancer Study", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rukh et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rukh et al. 2013) . A genotype score consisting of 24 risk alleles was not associated with snacking behavior in 7,502 European subjects ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00109-013-1027-z", "ISBN" : "0010901310", "ISSN" : "1432-1440", "PMID" : "23640704", "abstract" : "We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (\u03b2 = 0.180 [0.022-0.339], P value = 0.0258 and \u03b2 = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (\u03b2 = 0.151 [-0.006 to 0.309], P value = 0.0591 and \u03b2 = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.", "author" : [ { "dropping-particle" : "", "family" : "Robiou-du-Pont", "given" : "S\u00e9bastien", "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" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "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" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Mol Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "5", "3" ] ] }, "title" : "Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Robiou-du-Pont et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Robiou-du-Pont et al. 2013). A recent two-stage genome-wide association meta-analysis for macronutrient intake in more than 70,000 European subjects identified FTO and a new locus (FGF21) not previously associated with obesity as significant contributors to protein and carbohydrate / lipid intake, respectively ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/hmg/ddt032", "ISSN" : "1460-2083", "PMID" : "23372041", "abstract" : "Dietary intake of macronutrients (carbohydrate, protein, and fat) has been associated with risk of chronic conditions such as obesity and diabetes. Family studies have reported a moderate contribution of genetics to variation in macronutrient intake. In a genome-wide meta-analysis of a population-based discovery cohort (n = 33 533), rs838133 in FGF21 (19q13.33), rs197273 near TRAF family member-associated NF-kappa-B activator (TANK) (2p24.2), and rs10163409 in FTO (16q12.2) were among the top associations (P < 10(-5)) for percentage of total caloric intake from protein and carbohydrate. rs838133 was replicated in silico in an independent sample from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) Nutrition Working Group (n = 38 360) and attained genome-wide significance in combined analysis (Pjoint = 7.9 \u00d7 10(-9)). A cytokine involved in cellular metabolism, FGF21 is a potential susceptibility gene for obesity and type 2 diabetes. Our results highlight the potential of genetic variation for determining dietary macronutrient intake.", "author" : [ { "dropping-particle" : "", "family" : "Chu", "given" : "Audrey Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Workalemahu", "given" : "Tsegaselassie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Paynter", "given" : "Nina P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Lynda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Giulianini", "given" : "Franco", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ngwa", "given" : "Julius S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Qibin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curhan", "given" : "Gary C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimm", "given" : "Eric B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pasquale", "given" : "Louis R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ridker", "given" : "Paul M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Hum Mol Genet", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2013", "5", "1" ] ] }, "page" : "1895-1902", "title" : "Novel locus including FGF21 is associated with dietary macronutrient intake", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3945/ajcn.112.052183", "ISSN" : "1938-3207", "PMID" : "23636237", "abstract" : "BACKGROUND: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. OBJECTIVE: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. DESIGN: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 \u00d7 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. RESULTS: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (\u03b2 \u00b1 SE: 0.25 \u00b1 0.04%; P = 1.68 \u00d7 10(-8)) and lower fat (\u03b2 \u00b1 SE: -0.21 \u00b1 0.04%; P = 1.57 \u00d7 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (\u03b2 \u00b1 SE: 0.10 \u00b1 0.02%; P = 9.96 \u00d7 10(-10)), independent of BMI (after adjustment for BMI, \u03b2 \u00b1 SE: 0.08 \u00b1 0.02%; P = 3.15 \u00d7 10(-7)). CONCLUSION: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).", "author" : [ { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ngwa", "given" : "Julius S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rooij", "given" : "Frank J a", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wojczynski", "given" : "Mary K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frazier-Wood", "given" : "Alexis C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Houston", "given" : "Denise K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kanoni", "given" : "Stavroula", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lemaitre", "given" : "Rozenn N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mikkil\u00e4", "given" : "Vera", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Renstrom", "given" : "Frida", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chu", "given" : "Audrey Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oliveira Otto", "given" : "Marcia C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dhurandhar", "given" : "Emily J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feitosa", "given" : "Mary F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johansson", "given" : "Ingegerd", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lohman", "given" : "Kurt K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Manichaikul", "given" : "Ani", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McKeown", "given" : "Nicola M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mozaffarian", "given" : "Dariush", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singleton", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stirrups", "given" : "Kathleen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Viikari", "given" : "Jorma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ye", "given" : "Zheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bandinelli", "given" : "Stefania", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Forouhi", "given" : "Nita G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Yongmei", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyytik\u00e4inen", "given" : "Leo-Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "North", "given" : "Kari E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dimitriou", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hallmans", "given" : "Goran", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00e4h\u00f6nen", "given" : "Mika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Langenberg", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ordovas", "given" : "Jose M", "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" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalafati", "given" : "Ioanna-Panagiota", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raitakari", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franco", "given" : "Oscar H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emilsson", "given" : "Valur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schrack", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Semba", "given" : "Richard D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siscovick", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnett", "given" : "Donna K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borecki", "given" : "Ingrid 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" : "Kritchevsky", "given" : "Stephen B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtim\u00e4ki", "given" : "Terho", "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" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rotter", "given" : "Jerome I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "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" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dedoussis", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cupples", "given" : "L Adrienne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nettleton", "given" : "Jennifer a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "1395-1402", "title" : "Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake", "type" : "article-journal", "volume" : "97" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Chu et al. 2013; Tanaka et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Chu et al. 2013; Tanaka et al. 2013). Collectively, these data suggest that the genetic predisposition to polygenic obesity is at best selectively related to food intake and food behavior meaning that other possible mechanisms involved in genetic predisposition to obesity should be explored.The positive association between increased energy intake and BMI is well established ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1301/nr.2004.jul.S98", "author" : [ { "dropping-particle" : "", "family" : "Prentice", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jebb", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2004" ] ] }, "title" : "Energy Intake / Physical Activity Interactions in the Homeostasis of Body Weight Regulation", "type" : "article-journal", "volume" : "62" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Prentice and Jebb 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Prentice and Jebb 2004), however some questions still remain such as if increased energy intake is the cause of increased BMI or a consequence of it. Higher total energy intake has been associated with subsequent weight gain in children in longitudinal studies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Berkey", "given" : "Catherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rockett", "given" : "Helaine R H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Field", "given" : "Alison E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillman", "given" : "Matthew W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frazier", "given" : "Lindsay", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Camargo", "given" : "Carlos A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Colditz", "given" : "Graham A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatrics", "id" : "ITEM-1", "issue" : "56", "issued" : { "date-parts" : [ [ "2000" ] ] }, "title" : "Activity , Dietary Intake , and Weight Changes in a Longitudinal Study of Preadolescent and Adolescent Boys and Girls Lindsay Frazier , Carlos A . Camargo , Jr , MD and Graham A . Colditz The online version of this article , along with updated information", "type" : "article-journal", "volume" : "105" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Berkey et al. 2000)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Berkey et al. 2000) but the association between total energy intake and weight gain across time is controversial in adults ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "LM", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "TI", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schroll", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Int J Obes Relat Metab Disord", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "1995" ] ] }, "page" : "909-915", "title" : "Influence of dietary factors on weight change assessed by multivariate graphical models", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISBN" : "2005513946", "author" : [ { "dropping-particle" : "", "family" : "Halkjaer", "given" : "Jytte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tjonneland", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thomsen", "given" : "Birthe L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Overvad", "given" : "Kim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sorensen", "given" : "Thorkild IA", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "789-797", "title" : "Intake of macronutrients as predictors of 5-y changes in waist", "type" : "article-journal", "volume" : "84" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(J\u00f8rgensen et al. 1995; Halkjaer et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(J?rgensen et al. 1995; Halkjaer et al. 2006). This complex pattern of association may relate to the fact that increased BMI results in higher basal metabolic rates and higher energy requirements ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2012.109", "ISSN" : "1476-5497", "PMID" : "22825659", "abstract" : "OBJECTIVE: We investigated to what extent changes in metabolic rate and composition of weight loss explained the less-than-expected weight loss in obese men and women during a diet-plus-exercise intervention.\n\nDESIGN: In all, 16 obese men and women (41 \u00b1 9 years; body mass index (BMI) 39 \u00b1 6 kg\u2009m(-2)) were investigated in energy balance before, after and twice during a 12-week very-low-energy diet(565-650 kcal per day) plus exercise (aerobic plus resistance training) intervention. The relative energy deficit (EDef) from baseline requirements was severe (74%-87%). Body composition was measured by deuterium dilution and dual energy X-ray absorptiometry, and resting metabolic rate (RMR) was measured by indirect calorimetry. Fat mass (FM) and fat-free mass (FFM) were converted into energy equivalents using constants 9.45 kcal per g FM and 1.13 kcal per g FFM. Predicted weight loss was calculated from the EDef using the '7700 kcal\u2009kg(-1) rule'.\n\nRESULTS: Changes in weight (-18.6 \u00b1 5.0 kg), FM (-15.5 \u00b1 4.3 kg) and FFM (-3.1 \u00b1 1.9 kg) did not differ between genders. Measured weight loss was on average 67% of the predicted value, but ranged from 39% to 94%. Relative EDef was correlated with the decrease in RMR (R=0.70, P<0.01), and the decrease in RMR correlated with the difference between actual and expected weight loss (R=0.51, P<0.01). Changes in metabolic rate explained on average 67% of the less-than-expected weight loss, and variability in the proportion of weight lost as FM accounted for a further 5%. On average, after adjustment for changes in metabolic rate and body composition of weight lost, actual weight loss reached 90% of the predicted values.\n\nCONCLUSION: Although weight loss was 33% lower than predicted at baseline from standard energy equivalents, the majority of this differential was explained by physiological variables. Although lower-than-expected weight loss is often attributed to incomplete adherence to prescribed interventions, the influence of baseline calculation errors and metabolic downregulation should not be discounted.", "author" : [ { "dropping-particle" : "", "family" : "Byrne", "given" : "N M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schutz", "given" : "Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hills", "given" : "a P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of obesity (2005)", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2012", "11" ] ] }, "page" : "1472-8", "publisher" : "Nature Publishing Group", "title" : "Does metabolic compensation explain the majority of less-than-expected weight loss in obese adults during a short-term severe diet and exercise intervention?", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Byrne et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Byrne et al. 2012). This question also applies to genetic variants associated both with food-related traits and obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00109-013-1027-z", "ISBN" : "0010901310", "ISSN" : "1432-1440", "PMID" : "23640704", "abstract" : "We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (\u03b2 = 0.180 [0.022-0.339], P value = 0.0258 and \u03b2 = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (\u03b2 = 0.151 [-0.006 to 0.309], P value = 0.0591 and \u03b2 = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.", "author" : [ { "dropping-particle" : "", "family" : "Robiou-du-Pont", "given" : "S\u00e9bastien", "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" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "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" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Mol Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "5", "3" ] ] }, "title" : "Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Robiou-du-Pont et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Robiou-du-Pont et al. 2013). To gain more insight into the role of obesity predisposing SNPs on energy intake and macronutrient distribution, we investigated the association between 14 obesity predisposing SNPs as well as a genotype score on overall energy intake, macronutrients, different types of fat, using a validated FFQ in 1,850 Canadian subjects of European ancestry. 4.2 Methods4.2.1 ParticipantsThe EpiDREAM study included a total of 24,872 individuals from 191 centres in 21 countries who were screened for eligibility to enter in the DREAM clinical trial ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/1741826711409327", "ISSN" : "2047-4881", "PMID" : "21551215", "abstract" : "AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death. METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22). CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dagenais", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Probstfield", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freeman", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaw", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanas", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avezum", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budaj", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jung", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "H C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur J Prev Cardiol", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "755-764", "title" : "Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Anand et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Anand et al. 2012). All individuals who were deemed to be at risk for dysglycemia defined by family history, ethnicity and abdominal obesity, between the ages of 18 to 85 years, were screened using a 75 gram oral glucose tolerance test (OGTT) from July 2001 to August 2, 2003. Detailed methods and description of the study cohort have been described earlier ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1177/1741826711409327", "ISSN" : "2047-4881", "PMID" : "21551215", "abstract" : "AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death. METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22). CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.", "author" : [ { "dropping-particle" : "", "family" : "Anand", "given" : "S S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dagenais", "given" : "G R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mohan", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diaz", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Probstfield", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Freeman", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaw", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanas", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Avezum", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budaj", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jung", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Desai", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosch", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gerstein", "given" : "H C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eur J Prev Cardiol", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "755-764", "title" : "Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study.", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Anand et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Anand et al. 2012). We included in the present study 1,850 Canadian subjects of European ancestry having both FFQ and genotypic information available at baseline (Figure 2). All non-Canadians with FFQ data were removed because country specific FFQs were used, limiting the comparability of participants across countries. We excluded participants with >5% of FFQ data not filled out or those with implausible dietary intakes. Self-reported white European ethnicity has been validated using the Eigensoft software (). Samples that failed to cluster with individuals of European ancestry were removed. The EpiDREAM study has been approved by local ethics committee and informed consent was obtained from each subject before participating in the study, in accordance with the Declaration of Helsinki. 762005133975Figure 2. EpiDREAM Participant Flow Chart 00Figure 2. EpiDREAM Participant Flow Chart 4.2.2 PhenotypingHeight (m) and weight (kg) were measured in clinical centers by a trained medical staff. Standing height was measured to the nearest 0.1 cm with the participant looking straight ahead in bare feet and with his/her back against a wall. Weight was measured to the nearest 0.1 kg in light clothing. BMI was calculated as weight in kilograms (kg) divided by height in meters (m) squared.Diet was measured using a validated semiquantitative FFQ previously developed for the SHARE (Study of Health Assessment and Risk Evaluation) study. Pearson correlation coefficients between the diet records and FFQ in the European population ranged from 0.30 for polyunsaturated fat to 0.65 for saturated fat ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1053/jada.2003.50578", "ISSN" : "0002-8223", "PMID" : "12963948", "abstract" : "We developed three ethnic food frequency questionnaires (FFQs) to characterize the diets of South Asian, Chinese, and European immigrants. FFQs were developed from foods reported in the diet records and recalls of 29 South Asians, 25 Chinese, and 20 Europeans participating in a pilot study from 1995-1996 in Hamilton, Ontario, Canada. The FFQ and a seven-day diet record were then administered to 342 South Asians, 317 Chinese, and 346 Europeans participating in the Study of Health Assessment and Risk in Ethnic groups (SHARE) in three Canadian centers from 1996-1998. For FFQ validation, a subset of these participants completed a second seven-day diet record and second FFQ 8 to 10 months later. The FFQ generally underestimated macronutrient and overestimated micronutrient intake compared with the records. Consumption of most macronutrients was lower among South Asians. Energy-adjusted deattenuated correlation coefficients between the records and second FFQ ranged from 0.32 to 0.73 (South Asians), 0.17 to 0.84 (Chinese), and 0.30 to 0.83 (Europeans). The FFQs generally performed well and will be used to investigate diet-disease relations in SHARE. Lower correlations for dietary fats among Chinese persons (0.17 to 0.31) may be improved with more direct questions on the FFQ regarding brand, type, and amount of oil consumed in stirfry servings.", "author" : [ { "dropping-particle" : "", "family" : "Kelemen", "given" : "Linda E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anand", "given" : "Sonia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vuksan", "given" : "Vladimir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yi", "given" : "Qilong", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Teo", "given" : "Koon K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devanesen", "given" : "Sudarshan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yusuf", "given" : "Salim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Am Diet Assoc", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "1178-1184", "title" : "Development and evaluation of cultural food frequency questionnaires for South Asians, Chinese, and Europeans in North America.", "type" : "article-journal", "volume" : "103" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kelemen et al. 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kelemen et al. 2003). 4.2.3 GenotypingBuffy coats for DNA extraction have been collected from all willing participants of the EpiDREAM study. DNA has been extracted by the Gentra System. Genotyping was performed using the Illumina CVD bead chip microarray ITMAT Broad Care (IBC) array ADDIN 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" : { "previouslyFormattedCitation" : "(Keating et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keating et al. 2008). Genotyping was performed at the McGill University and Genome Quebec Innovation Centre using the Illumina Bead Studio genotyping module, version 3.2. Marker with a missing call rate of greater than 10% and individuals with a 3% or greater call rate were removed, as well as marker with a minor allele frequency of less than 0.00001. We selected 14 SNPs that display genome-wide significant association (P<5×10-8) for BMI and?/?or binary obesity status in the literature and were genotyped on the versions 1 and 2 of the IBC 50K SNP array. The 14 SNPs are: rs1514176 (TNN13K), rs6235 (PCSK1), rs6232 (PCSK1), rs2206734 (CDKAL1), rs2272903 (TFAP2B), rs1211166 (NTRK2), rs6265 (BDNF), rs1401635 (BDNF), rs997295 (MAP2K5), rs7203521 (FTO), rs9939609 (FTO), rs1805081 (NPC1), rs2075650 (TOMM40/APOE/APOC1), rs11671664 (GIPR). The 14 SNPs showed no deviation from Hardy-Weinberg equilibrium (HWE) (all left5959475Table 2: Genotypic Information for Obesity Predisposing SNPs00Table 2: Genotypic Information for Obesity Predisposing SNPsP > 0.06, Table 2. The call rate for each of the 14 SNPs was 100%.GeneSNPRisk AlleleMajor AlleleMinor AlleleGenotype CountGenotyping Call Rate (%)HWE p-valueTNN13Krs1514176GAG650 893 3071000.9922PCSK1rs6235CGC1018 693 1391000.1639PCSK1rs6232GAG1660 187 31000.3389CDKAL1rs2206734CCT1179 606 651000.2314TFAP2Brs2272903GGA1494 341 151000.3535NTRK2rs1211166AAG1212 565 731000.4828BDNFrs6265GGA1213 577 601000.3903BDNFrs1401635CGC932 748 1701000.2611MAP2K5rs997295TTG670 885 2951000.9230FTOrs7203521AAG746 828 2761000.0637FTOrs9939609ATA639 871 3401000.1543NPC1rs1805081AAG662 891 2971000.9227TOMM40/APOE/APOC1rs2075650AAG1400 413 371000.3140GIRP rs11671664GAA1478 351 211000.97494.2.4 Statistical methodsStatistical analyses were performed using SPSS ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "IBM Corp", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "number" : "20.0", "publisher" : "IBM Corp", "publisher-place" : "Armonk, NY", "title" : "IBM SPSS Statistics for Windows", "type" : "article" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(IBM Corp 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(IBM Corp 2011). The overlap of information between nutrition measures was assessed using Pearson correlation. For each of the 14SNPs, the previously identified obesity risk allele was used as the risk allele. Single SNP analyses were performed under the additive model. A genotype score was calculated by summing the alleles predisposing to obesity for the 14 SNPs so that the score ranged from 0 to 28. We used a unweighted score as Janssen et al ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/GIM.0b013e31812eece0", "ISSN" : "1098-3600", "author" : [ { "dropping-particle" : "", "family" : "Janssens", "given" : "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" : "Genet Med", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2007", "8" ] ] }, "page" : "528-535", "title" : "The impact of genotype frequencies on the clinical validity of genomic profiling for predicting common chronic diseases", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "(2007)", "previouslyFormattedCitation" : "(Janssens et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(2007). previously showed that weighting had no major impact on the score. We constructed multivariate linear regression models to determine the effect of each of the 14 SNPS and the genotype score on BMI in addition to food consumption parameters. The regression models were adjusted for sex, age and BMI. To determine the effect of the relative intake of nutrients independent of caloric intake, nutrient intakes were adjusted for caloric intake by regression analysis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-9262", "PMID" : "8484372", "author" : [ { "dropping-particle" : "", "family" : "Willett", "given" : "Walter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stampfer", "given" : "Meir J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Epidemiol", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "1986", "4", "1" ] ] }, "page" : "17-27", "title" : "Re: \"Total energy intake: implications for epidemiologic analyses\".", "type" : "article-journal", "volume" : "124" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Willett and Stampfer 1986)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Willett and Stampfer 1986). Two-tailed P-values are presented in this manuscript and P < 0.05 were considered as nominally significant. After applying a Bonferroni’s correction for multiple testing, a p <1.754x10-4 (0.05/285 tests) was considered as significant. QUANTO ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Gauderman", "given" : "Jim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morrison", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2001" ] ] }, "publisher" : "Department of Preventive Medicine, University of Southern California", "publisher-place" : "Los Angeles, California", "title" : "QUANTO", "type" : "article" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Gauderman and Morrison 2001)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Gauderman and Morrison 2001), was used to measure the power of finding an association between individual SNPs and BMI for varying allelic frequencies and beta-coefficients (Figure 3) .AB184152566670Figure 3. Statistical power for detecting associations between individual SNPs and BMI according to allele frequency and beta-coefficients with a sample size of 1,850 participants. A – Power for testing associations according to risk allele frequency and beta-coefficient, assuming a two-sided P-value of 0.05 unadjusted for multiple testing. B – Power for resting associations according to risk allele frequency and beta-coefficient, assuming a two-sided P-value of 1.754x10-4 after adjustment for multiple testing. 00Figure 3. Statistical power for detecting associations between individual SNPs and BMI according to allele frequency and beta-coefficients with a sample size of 1,850 participants. A – Power for testing associations according to risk allele frequency and beta-coefficient, assuming a two-sided P-value of 0.05 unadjusted for multiple testing. B – Power for resting associations according to risk allele frequency and beta-coefficient, assuming a two-sided P-value of 1.754x10-4 after adjustment for multiple testing. 4.3 Results left6620510Table 3: EpiDREAM Participant Characteristics00Table 3: EpiDREAM Participant CharacteristicsTable 3 describes the characteristics of the 1,850 study participants. The different nutrient components (total energy, total fat, saturated fat, monounsaturated fat (MUFA), polyunsaturated fat (PUFA), trans-fat, carbohydrates and protein) were all significantly correlated with each other in the study (Pearson correlation coefficient range 0.311 to 0.986; Table 4). The correlation between carbohydrates and total fat and fat subcomponents was more modest, as well as the correlation between trans-fat and all other nutrient components. BMI was significantly associated with total energy intake as well as all energy-adjusted nutrients (Table 5). All (n=1850)Males (n=643, 34.8%)Females (n=1207, 65.2%)Age53.07 (+/- 10.579)55.20 (+/- 10.850)51.93 (+/- 10.256)BMI (kg/m2)30.83 (+/-6.441)30.37 (+/- 5.172)31.07 (+/- 7.014)Total energy (kcal)1891.75 (+/- 657.076)2103.13 (+/- 691.026)1779.15 (+/- 609.286)Total fat (g/day)64.90 (+/- 27.354)72.19 (+/- 30.655)61.02 (+/- 24.257)Saturated fat (g/day)22.24 (+/- 10.278)24.92 (+/- 11.531)20.82 (+/- 9.237)Monounsaturated fat (g/day)24.82 (+/- 11.031)27.90 (+/- 12.405)23.19 (+/- 9.845)Polyunsaturated fat (g/day)9.86 (+/- 4.477)10.85 (+/-4.979)9.33 (+/- 4.091)Trans fat (g/day)0.63 (+/- 0.739)0.71 (+/- 0.805)0.591 (+/- 0.699)Carbohydrates (g/day)241.84 (+/- 91.252)263.48 (+/- 95.074)230.31 (+/- 87.016)Protein (g/day)82.636 (+/- 31.146)89.11 (+/- 32.606)79.19 (+/- 29.783)EnergyTotal FatSaturated FatMonounsaturated FatPolyunsaturated FatTrans FatCarbohydratesProteinEnergy0.8780.8190.8440.8190.4160.910.882Total Fat0.9510.9860.9180.5230.6520.844Saturated Fat0.9120.7690.4630.5930.787Monounsaturated Fat0.9360.530.6050.816Polyunsaturated Fat0.5730.6310.774Trans Fat0.3120.311Carbohydrates0.711Protein-68580208915Table 4: Pearson Correlations for Unadjusted Nutrient Intakes00Table 4: Pearson Correlations for Unadjusted Nutrient IntakesAll correlations significant at the 0.01 level (two-tailed) left2419350Table 5: Association of Energy and Energy Adjusted Nutrients with BMI 00Table 5: Association of Energy and Energy Adjusted Nutrients with BMI Association with BMIBetaSEp-valueEnergy0.0012.340E-040.002Total Fat0.0570.0123.000E-06Saturated Fat0.0800.0270.003Monounsaturated Fat0.1170.0271.700E-05Polyunsaturated Fat0.2430.0604.900E-05Trans Fat0.6030.2390.012Carbohydrates-0.0110.0040.006Protein0.0370.0103.640E-044.3.1 Association of obesity predisposing SNPs and genotype score with BMITwo out of 14 SNPs showed a directionally consistent and nominally significant association with BMI: rs9939609 SNP in FTO (beta = 0.72 ± 0.21, P = 0.001) and rs1514176 in TNNI3K (beta = 0.57 ± 0.21, P = 0.008) (Table 6). The genotype score was also positively associated with BMI (beta / per additional risk allele = 0.14 ± 0.06, P = 0.03). Further adjustment for total energy intake did not modify the association between rs9939609 and rs1514176 SNPs in FTO and TNNI3K or the genotype score and BMI (Table 5).Gene/SNPTNN13K - rs1514176PCSK1 - rs6235PCSK1 - rs6232CDKAL1 - rs2206734TFAP2B - rs2272903NTRK2 - rs1211166BDNF - rs6265BDNF - rs1401635MAP2K5 - rs997295FTO - rs7203521FTO - rs9939609NPC1 - rs1805081TOMM40/APOE/APOC1 - rs2075650GIRP - rs11671664Gene ScoreBMIbeta0.571-0.228-0.0650.2460.0030.033-0.0550.302-0.0710.0890.7170.053-0.3600.3360.140SE0.2150.2370.4810.2690.3560.2660.2730.2290.2160.2140.2100.2160.3090.3430.064p-value0.0080.3360.8930.3600.9930.9000.8420.1870.7440.6780.0010.8060.2440.3280.030BMI adjusted for total energy intakebeta0.552-0.256-0.0380.2400.0280.035-0.0890.264-0.0610.1080.7210.041-0.3700.3080.132SE0.2150.2360.4800.2680.3550.2660.2730.2290.2150.2140.2100.2160.3090.3430.064p-value0.0100.2780.9370.3710.9370.8950.7430.2500.7760.6130.0010.8480.2310.3680.039Total Energy Intakebeta0.0180.028-0.0160.012-0.0150.0010.0220.026-0.007-0.011-0.0010.0100.0040.0250.007SE0.0120.0130.0260.0150.0190.0140.0150.0120.0120.0120.0110.0120.0170.0190.003p-value0.1150.0280.5500.4110.4310.9320.1380.0340.5700.3310.9220.4070.8270.1800.039Total Fatbeta0.011-0.0100.0000.002-0.004-0.0100.0180.017-0.007-0.011-0.0010.002-0.0010.0150.001SE0.0070.0070.0150.0080.0110.0080.0090.0070.0070.0070.0070.0070.0100.0110.002p-value0.1020.1970.9930.7690.7150.2220.0320.0200.2810.0910.8810.7760.8920.1770.662Saturated Fatbeta0.013-0.0140.010-0.002-0.011-0.0140.0160.0160.001-0.015-0.007-0.005-0.0040.008-0.001SE0.0090.0100.0200.0110.0150.0110.0110.0090.0090.0090.0090.0090.0130.0140.003p-value0.1490.1550.6130.8280.4450.2120.1640.0830.9230.0960.3970.6040.7570.5490.689MUFAbeta0.013-0.0120.0010.002-0.004-0.0080.0210.017-0.014-0.0130.0040.0050.0020.0200.001SE0.0080.0090.0180.0100.0130.0100.0100.0080.0080.0080.0080.0080.0110.0130.002p-value0.1070.1870.9450.8740.7420.3950.0360.0460.0800.0900.5710.5650.8590.1070.540PUFAbeta0.017-0.008-0.0120.0080.008-0.0100.0290.024-0.020-0.0070.0100.0070.0000.0130.004SE0.0080.0090.0190.0110.0140.0100.0110.0090.0080.0080.0080.0080.0120.0130.003p-value0.0500.4030.5230.4230.5650.3230.0070.0080.0170.3860.2230.3920.9700.3460.126Trans Fatbeta0.068-0.0150.0930.0030.034-0.0900.0220.0900.004-0.003-0.009-0.013-0.042-0.0520.005SE0.0310.0340.0690.0390.0510.0380.0390.0330.0310.0310.0300.0310.0450.0490.009p-value0.0290.6710.1780.9330.5050.0190.5760.0060.8890.9290.7580.6780.3420.2890.558Carbohydratesbeta-0.0090.0100.0020.004-0.0020.002-0.009-0.0040.0050.002-0.001-0.005-0.006-0.001-0.001SE0.0050.0060.0120.0070.0090.0070.0070.0060.0050.0050.0050.0050.0080.0090.002p-value0.1130.0790.8600.5770.7970.7580.1920.4710.3500.6630.9210.3370.4580.8660.679Proteinbeta-0.0050.002-0.0040.0010.0010.0040.001-0.004-0.0110.0050.0050.005-0.0010.0020.000SE0.0060.0070.0130.0080.0100.0070.0080.0060.0060.0060.0060.0060.0090.0100.002p-value0.4330.7820.7810.9440.9280.6050.8730.5500.0660.3630.3710.4170.8650.8750.948right155575Table 6: The Association of Obesity Predisposing SNPs with BMI and Energy Adjusted Nutrients020000Table 6: The Association of Obesity Predisposing SNPs with BMI and Energy Adjusted Nutrients4.3.2 Association of obesity predisposing SNPs and genotype score with dietary intake parameters Six out of the 14 SNPs and the genotype score displayed nominally significant associations with at least one energy adjusted dietary intake parameter: rs1514176 (TNN13K) with trans-fat (beta = 0.068 ± 0.031, p = 0.029), rs6235 (PCSK1) with total energy (beta = 0.028 ± 0.013, p = 0.028), rs1211166 (NTRK2) with trans-fat (beta = -0.09 ± 0.038, p = 0.019), rs6265 (BDNF) with total fat (beta = 0.018 ± 0.009, p = 0.032), MUFA (beta = 0.021 ± 0.01, p = 0.036), and PUFA (beta = 0.029 ± 0.011, p = 0.007), rs1401635 (BDNF) with total energy (beta = 0.026 ± 0.012, p = 0.034), total fat (beta = 0.017 ± 0.007, p = 0.020), MUFA (beta = 0.017 ± 0.008, p = 0.046), PUFA (beta = 0.024 ± 0.009, p = 0.008), and trans fat (beta = 0.090 ± 0.033, p = 0.006), rs997295 (MAP2K5) with PUFA (beta = -0.020 ± 0.008, p = 0.017), and the genotype score with total energy (beta/ additional risk allele = 0.007 ± 0.003, p = 0.039). Further adjustment for BMI did not significantly modify any of the relationships (Table 6). 4.4 Discussion This study confirms the association of BMI with total energy intake, macronutrient intake, and the subcomponents of fat as well as the association of rs9939609 (FTO) and rs1514176 (TNN13K), and genotype score with BMI in a North American population of European ancestry. Six of the 14 SNPs as well as the genotype score were nominally associated with at least one of the dietary intake parameters. Of particular interest was the association between two separate SNPs located in or near BDNF (rs6265 and rs1401635), with total fat, MUFA, and PUFA intake with rs1401635 also being associated with total energy and trans-fat intake. The study also found an association between rs6235 (PCSK1) and the genotype score and total energy intake. After applying the Bonferroni correction to adjust for the 285 tests conducted for analysis a p-value <1.754x10-4 was considered significant. After adjustment, only the association between total fat, MUFA, and PUFA intake with BMI remained significant. Because our results are otherwise nominally significant, at least some of them are likely false positive results. However, the literature supports most of our results, though the more novel discoveries require further replication. We replicated findings of the association of FTO ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng2048", "ISSN" : "1061-4036", "PMID" : "17496892", "abstract" : "We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.", "author" : [ { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gallina", "given" : "Sophie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6rner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlsson", "given" : "Lena M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiess", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vatin", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delplanque", "given" : "J\u00e9rome", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vaillant", "given" : "Emmanuel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruiz", "given" : "Juan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weill", "given" : "Jacques", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levy-Marchal", "given" : "Claire", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potoczna", "given" : "Natascha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stunff", "given" : "Catherine", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bougn\u00e8res", "given" : "Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cauchi", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ch\u00e8vre", "given" : "Jean-Claude", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Genet", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2007", "6" ] ] }, "page" : "724-726", "title" : "Variation in FTO contributes to childhood obesity and severe adult obesity", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1126/science.1141634", "ISSN" : "1095-9203", "PMID" : "17434869", "abstract" : "Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetes-susceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.", "author" : [ { "dropping-particle" : "", "family" : "Frayling", "given" : "Timothy M", "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" : "Freathy", "given" : "Rachel M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "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" : "Elliott", "given" : "Katherine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lango", "given" : "Hana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Nigel W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shields", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harries", "given" : "Lorna W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barrett", "given" : "Jeffrey C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellard", "given" : "Sian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groves", "given" : "Christopher J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Knight", "given" : "Bridget", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patch", "given" : "Ann-Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ness", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lawlor", "given" : "Debbie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "Susan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ben-Shlomo", "given" : "Yoav", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sovio", "given" : "Ulla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melzer", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "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" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karpe", "given" : "Fredrik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Owen", "given" : "Katharine R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cardon", "given" : "Lon R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitman", "given" : "Graham a", "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" : "Morris", "given" : "Andrew D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "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" : "" } ], "container-title" : "Science", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2007", "5", "11" ] ] }, "page" : "889-894", "title" : "A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity", "type" : "article-journal", "volume" : "316" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/ng.287", "ISSN" : "1546-1718", "PMID" : "19079261", "abstract" : "Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.", "author" : [ { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speliotes", "given" : "Elizabeth K", "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" : "Li", "given" : "Shengxu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heid", "given" : "Iris M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berndt", "given" : "Sonja I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lamina", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lettre", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Noha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyon", "given" : "Helen N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papadakis", "given" : "Konstantinos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Leonie C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bingham", "given" : "Sheila a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Morris", "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" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Connell", "given" : "John M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dennison", "given" : "Elaine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estrada", "given" : "Karol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillson", "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" : "Hackett", "given" : "Rachel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadley", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Alistair S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Havulinna", "given" : "Aki S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Kevin B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousilahti", "given" : "Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jovanovic", "given" : "Zorica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuokkanen", "given" : "Mikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laitinen", "given" : "Jaana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakatta", "given" : "Edward G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luben", "given" : "Robert N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McArdle", "given" : "Wendy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meitinger", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulas", "given" : "Antonella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munroe", "given" : "Patricia B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ness", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Northstone", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purmann", "given" : "Carolin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ridderstr\u00e5le", "given" : "Martin", "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" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder S", "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" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sims", "given" : "Matthew a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stephens", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Suzanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tung", "given" : "Y C Loraine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "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" : "Vimaleswaran", "given" : "Karani S", "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" : "Wallace", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "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" : "Nicholas", "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" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chanock", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guralnik", "given" : "Jack 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" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Ken K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouwehand", "given" : "Willem H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samani", "given" : "Nilesh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "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" : "Uda", "given" : "Manuela", "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" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panagiotis", "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 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayes", "given" : "Richard B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strachan", "given" : "David P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H-Erich", "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" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Genetics", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "page" : "25-34", "title" : "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Dina et al. 2007; Frayling et al. 2007; Willer et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Dina et al. 2007; Frayling et al. 2007; Willer et al. 2009), and TNNI3K ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.287", "ISSN" : "1546-1718", "PMID" : "19079261", "abstract" : "Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.", "author" : [ { "dropping-particle" : "", "family" : "Willer", "given" : "Cristen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Speliotes", "given" : "Elizabeth K", "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" : "Li", "given" : "Shengxu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lindgren", "given" : "Cecilia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heid", "given" : "Iris M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berndt", "given" : "Sonja I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Amanda L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Anne U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lamina", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lettre", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lim", "given" : "Noha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lyon", "given" : "Helen N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McCarroll", "given" : "Steven a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papadakis", "given" : "Konstantinos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Qi", "given" : "Lu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Randall", "given" : "Joshua C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roccasecca", "given" : "Rosa Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sanna", "given" : "Serena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scheet", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weedon", "given" : "Michael N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jing Hua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Leonie C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokopenko", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Soranzo", "given" : "Nicole", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tanaka", "given" : "Toshiko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Almgren", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bennett", "given" : "Amanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergman", "given" : "Richard N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bingham", "given" : "Sheila a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bonnycastle", "given" : "Lori L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Morris", "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" : "Chines", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coin", "given" : "Lachlan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Collins", "given" : "Francis S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Connell", "given" : "John M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cooper", "given" : "Cyrus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dennison", "given" : "Elaine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deodhar", "given" : "Parimal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdos", "given" : "Michael R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Estrada", "given" : "Karol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gianniny", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gieger", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillson", "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" : "Hackett", "given" : "Rachel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hadley", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Alistair S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Havulinna", "given" : "Aki S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hofman", "given" : "Albert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isomaa", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Kevin B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Toby", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jousilahti", "given" : "Pekka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jovanovic", "given" : "Zorica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khaw", "given" : "Kay-Tee", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuokkanen", "given" : "Mikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuusisto", "given" : "Johanna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laitinen", "given" : "Jaana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lakatta", "given" : "Edward G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luan", "given" : "Jian'an", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luben", "given" : "Robert N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangino", "given" : "Massimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McArdle", "given" : "Wendy L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meitinger", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mulas", "given" : "Antonella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munroe", "given" : "Patricia B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narisu", "given" : "Narisu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ness", "given" : "Andrew R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Northstone", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Purmann", "given" : "Carolin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rees", "given" : "Matthew G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ridderstr\u00e5le", "given" : "Martin", "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" : "Ruokonen", "given" : "Aimo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandhu", "given" : "Manjinder S", "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" : "Laura J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scuteri", "given" : "Angelo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silander", "given" : "Kaisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sims", "given" : "Matthew a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Song", "given" : "Kijoung", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stephens", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stevens", "given" : "Suzanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stringham", "given" : "Heather M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tung", "given" : "Y C Loraine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valle", "given" : "Timo T", "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" : "Vimaleswaran", "given" : "Karani S", "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" : "Wallace", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watanabe", "given" : "Richard M", "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" : "Nicholas", "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" : "Zeggini", "given" : "Eleftheria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhai", "given" : "Guangju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zillikens", "given" : "M Carola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altshuler", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caulfield", "given" : "Mark J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chanock", "given" : "Stephen J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrucci", "given" : "Luigi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guralnik", "given" : "Jack 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" : "Hu", "given" : "Frank B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laakso", "given" : "Markku", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mooser", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ong", "given" : "Ken K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouwehand", "given" : "Willem H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salomaa", "given" : "Veikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Samani", "given" : "Nilesh J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Spector", "given" : "Timothy D", "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" : "Uda", "given" : "Manuela", "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" : "Wareham", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deloukas", "given" : "Panagiotis", "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 C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hayes", "given" : "Richard B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Peltonen", "given" : "Leena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schlessinger", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strachan", "given" : "David P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H-Erich", "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" : "Abecasis", "given" : "Gon\u00e7alo R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "page" : "25-34", "title" : "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/ijo.2011.202", "ISSN" : "1476-5497", "PMID" : "22041983", "abstract" : "Obesity is a risk factor for multiple disorders such as diabetes and cardiovascular disease. Recently, a genome-wide association study for body mass index (BMI) was conducted in 249 796 individuals of European ancestry by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. They identified 14 known obesity susceptibility loci and 18 new loci associated with BMI at the genome-wide significance level (P<5 \u00d7 10\u207b\u2078). Because the prevalence and severity of obesity vary among ethnic groups, it is worthy to investigate these results in another ethnic population. We examined the BMI association of 19 single-nucleotide polymorphisms (SNPs) out of the 32 in 8842 individuals from the Korean Association Resource data, and found 12 SNPs to be associated with BMI in the Korean population. Eight loci, rs10968576 (BDNF), rs3817334 (MTCH2), rs1558902 (FTO), rs571312 (MC4R), rs543874 (SEC16B), rs987237 (TFAP2B), rs2867125 (TMEM18) and rs7138803 (FAIM2), were previously known obesity susceptibility loci, and the remaining four loci, rs1514175 (TNNI3K), rs206936 (NUDT3), rs4771122 (MTIF3) and rs2241423 (MAP2K5), were newly identified as BMI loci by the GIANT study. Further, all 12 SNPs showed the same direction of effect on BMI between the two ethnic groups, suggesting a similar genetic architecture governing the obesity.", "author" : [ { "dropping-particle" : "", "family" : "Hong", "given" : "K W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oh", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-2", "issue" : "8", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "1127-30", "title" : "Recapitulation of genome-wide association studies on body mass index in the Korean population.", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/oby.20592", "ISSN" : "1930-739X", "PMID" : "23929626", "abstract" : "OBJECTIVE: Many confirmed genetic loci for obesity are expressed in regions of the brain that regulate energy intake and reward-seeking behavior. Whether these loci contribute to the development of specific eating behaviors has not been investigated. The relationship between a genetic susceptibility to obesity and cognitive restraint, uncontrolled and emotional eating was examined. METHODS: Eating behavior and body mass index (BMI) were determined by questionnaires for 1471 men and 2381 women from two US cohorts. Genotypes were extracted from genome-wide scans and a genetic-risk score (GRS) derived from 32 obesity-loci was calculated. RESULTS: The GRS was positively associated with emotional and uncontrolled eating (P<0.002). In exploratory analysis, BMI-increasing variants of MTCH2, TNNI3K, and ZC3H4 were positively associated with emotional eating and those of TNNI3K and ZC3H4 were positively associated with uncontrolled eating. The BMI-increasing variant of FTO was positively and those of LRP1B and TFAP2B were inversely associated with cognitive restraint. These associations for single SNPs were independent of BMI but were not significant after multiple-testing correction. CONCLUSIONS: An overall genetic susceptibility to obesity may also extend to eating behaviors. The link between specific loci and obesity may be mediated by eating behavior but larger studies are warranted to confirm these results.", "author" : [ { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimm", "given" : "Eric B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curhan", "given" : "Gary C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-4", "issue" : "5", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "135-141", "title" : "Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Willer et al. 2009; Hong and Oh 2012; Mccaffery et al. 2012; Cornelis et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Willer et al. 2009; Hong and Oh 2012; Mccaffery et al. 2012; Cornelis et al. 2014) with BMI. The lack of association of other SNPs with BMI reflects the modest power of the study, supported by the nominal association of the 14 SNP genotype score with BMI. Though we did not find a significant association between either BDNF SNPs with BMI in the current study, the association between BDNF and obesity is well established with BDNF being linked to both monogenic hyperphagic obesity (Gray Diabetes 2006) and polygenic human obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.274", "ISSN" : "1546-1718", "PMID" : "19079260", "abstract" : "Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.", "author" : [ { "dropping-particle" : "", "family" : "Thorleifsson", "given" : "Gudmar", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walters", "given" : "G Bragi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudbjartsson", "given" : "Daniel F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steinthorsdottir", "given" : "Valgerdur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sulem", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Helgadottir", "given" : "Anna", "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" : "Thorlacius", "given" : "Steinunn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsdottir", "given" : "Ingileif", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsdottir", "given" : "Thorbjorg", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olafsdottir", "given" : "Elinborg J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Olafsdottir", "given" : "Gudridur H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Thorvaldur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jonsson", "given" : "Frosti", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jorgensen", "given" : "Torben", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lauritzen", "given" : "Torsten", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aben", "given" : "Katja K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verbeek", "given" : "Andr\u00e9 L M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roeleveld", "given" : "Nel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kampman", "given" : "Ellen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yanek", "given" : "Lisa R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Lewis C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tryggvadottir", "given" : "Laufey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rafnar", "given" : "Thorunn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Diane M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gulcher", "given" : "Jeffrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiemeney", "given" : "Lambertus a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Oluf", "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" : "" } ], "container-title" : "Nature genetics", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2009", "1" ] ] }, "page" : "18-24", "title" : "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity", "type" : "article-journal", "volume" : "41" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Thorleifsson et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Thorleifsson et al. 2009). In mouse models, heterozygous BDNF+/- are hyperphagic and gain significant weight in young adulthood compared to wild type mice ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0027-8424", "PMID" : "10611369", "abstract" : "Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the central nervous system. However, the role of endogenous BDNF in the development and function of these neurons has not been established in vivo because of the early postnatal lethality of BDNF null mice. In the present study, we use heterozygous BDNF(+/-) mice that have a normal life span and show that these animals develop enhanced intermale aggressiveness and hyperphagia accompanied by significant weight gain in early adulthood; these behavioral abnormalities are known to correlate with 5-HT dysfunction. Forebrain 5-HT levels and fiber density in BDNF(+/-) mice are normal at an early age but undergo premature age-associated decrements. However, young adult BDNF(+/-) mice show a blunted c-fos induction by the specific serotonin releaser-uptake inhibitor dexfenfluramine and alterations in the expression of several 5-HT receptors in the cortex, hippocampus, and hypothalamus. The heightened aggressiveness can be ameliorated by the selective serotonin reuptake inhibitor fluoxetine. Our results indicate that endogenous BDNF is critical for the normal development and function of central 5-HT neurons and for the elaboration of behaviors that depend on these nerve cells. Therefore, BDNF(+/-) mice may provide a useful model to study human psychiatric disorders attributed to dysfunction of serotonergic neurons.", "author" : [ { "dropping-particle" : "", "family" : "Lyons", "given" : "W E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mamounas", "given" : "L a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ricaurte", "given" : "G a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coppola", "given" : "V", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reid", "given" : "S W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bora", "given" : "S H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wihler", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koliatsos", "given" : "V E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tessarollo", "given" : "L", "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" : "26", "issued" : { "date-parts" : [ [ "1999", "12", "21" ] ] }, "page" : "15239-44", "title" : "Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities.", "type" : "article-journal", "volume" : "96" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Lyons et al. 1999)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Lyons et al. 1999). Mice which have BDNF eliminated from the brain after birth similarly display hyperphagia, consuming 74% more food and experiencing a 80-150% increase in body weight compared to controls ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/mend.15.10.0706", "ISSN" : "0888-8809", "PMID" : "11579207", "abstract" : "Brain-derived neurotrophic factor has been associated previously with the regulation of food intake. To help elucidate the role of this neurotrophin in weight regulation, we have generated conditional mutants in which brain-derived neurotrophic factor has been eliminated from the brain after birth through the use of the cre-loxP recombination system. Brain-derived neurotrophic factor conditional mutants were hyperactive after exposure to stressors and had higher levels of anxiety when evaluated in the light/dark exploration test. They also had mature onset obesity characterized by a dramatic 80-150% increase in body weight, increased linear growth, and elevated serum levels of leptin, insulin, glucose, and cholesterol. In addition, the mutants had an abnormal starvation response and elevated basal levels of POMC, an anorexigenic factor and the precursor for alpha-MSH. Our results demonstrate that brain derived neurotrophic factor has an essential maintenance function in the regulation of anxiety-related behavior and in food intake through central mediators in both the basal and fasted state.", "author" : [ { "dropping-particle" : "", "family" : "Rios", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fan", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fekete", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bates", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuehn", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lechan", "given" : "R M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jaenisch", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular endocrinology (Baltimore, Md.)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2001", "10" ] ] }, "page" : "1748-57", "title" : "Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity.", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rios et al. 2001)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rios et al. 2001). Additionally, BDNF (rs925946) has previously been found to be associated with food related behaviours, such as increased snacking ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00109-013-1027-z", "ISBN" : "0010901310", "ISSN" : "1432-1440", "PMID" : "23640704", "abstract" : "We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (\u03b2 = 0.180 [0.022-0.339], P value = 0.0258 and \u03b2 = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (\u03b2 = 0.151 [-0.006 to 0.309], P value = 0.0591 and \u03b2 = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.", "author" : [ { "dropping-particle" : "", "family" : "Robiou-du-Pont", "given" : "S\u00e9bastien", "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" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "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" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Mol Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "5", "3" ] ] }, "title" : "Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Robiou-du-Pont et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Robiou-du-Pont et al. 2013) and increased energy consumption (rs10767664 and rs6265) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mccaffery et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mccaffery et al. 2012). No previous studies have found an association between BDNF risk variants and fat consumption, however an association between BDNF and an increased number of servings of both dairy products and products from the meat, eggs, nuts, and beans food group was found ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.111.026955.The", "author" : [ { "dropping-particle" : "", "family" : "Mccaffery", "given" : "Jeanne M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papandonatos", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peter", "given" : "Inga", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Huggins", "given" : "Gordon S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raynor", "given" : "Hollie A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Delahanty", "given" : "Linda M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cheskin", "given" : "Lawrence J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balasubramanyam", "given" : "Ashok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wagenknecht", "given" : "Lynne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wing", "given" : "Rena R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subgroup", "given" : "Genetic", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1477-1486", "title" : "Obesity susceptibility loci and dietary intake in the Look AHEAD Trial", "type" : "article-journal", "volume" : "95" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mccaffery et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mccaffery et al. 2012). Dairy products as well as meat, eggs, and nuts, can be higher sources of fat in the diet therefore potentially supporting a link between BDNF risk variants and higher fat consumption. Additional evidence of a link between BDNF and fat consumption comes from mice models in which young BDNF mutants experienced premature development of hyperphagia when fed a high fat diet but not when fed a balanced diet ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fox", "given" : "Edward A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Byerly", "given" : "Mardi S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "994-1004", "title" : "Physiological Regulation of Appetite A mechanism underlying mature-onset obesity : evidence from the hyperphagic phenotype of brain-derived neurotrophic factor mutants", "type" : "article-journal", "volume" : "47907" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fox and Byerly 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fox and Byerly 2004). In this study, two BDNF variants were associated with total fat, MUFA, and PUFA consumption reducing the likelihood that the relationship is a spurious result. Similarly to BDNF, PCSK1, is linked to both monogenic hyperphagic obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1210/jc.2007-0687", "ISSN" : "0021-972X", "PMID" : "17595246", "abstract" : "CONTEXT: Congenital deficiency of the neuroendocrine-specific enzyme prohormone convertase (PC) 1/3 leads to a syndrome characterized by obesity, small intestinal dysfunction, and dysregulation of glucose homeostasis in humans. To date, only two unrelated subjects with this disorder have been reported. Research DESIGN AND METHODS: We now report a third proband, a 6-yr-old boy, offspring of a consanguineous union of parents of North African origin, who was homozygous for a novel missense mutation Ser307Leu. We characterized the functional properties of the mutant PC1/3 and characterized the clinical phenotype of the patient. RESULTS: In vitro this mutation markedly impairs the catalytic activity of the convertase. However, in contrast to other previously described naturally occurring mutations, intracellular trafficking of this mutant enzyme appeared normal. The Ser307Leu mutant retained some autocatalytic activity, even though it was completely inactive on other substrates. As with the previous two patients, this child had obesity and persistent diarrhea, however, there was no history of reactive hypoglycemia. The patient showed markedly increased food intake at an ad libitum test meal, confirming that hyperphagia makes a major contribution to the obesity seen in this syndrome. CONCLUSION: This case extends the clinical and molecular spectrum of human congenital PC1/3 deficiency.", "author" : [ { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Volders", "given" : "Karolien", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stanhope", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heuschkel", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "White", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lank", "given" : "Emma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Keogh", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Creemers", "given" : "John W M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Journal of Clinical Endocrinology and Metabolism", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2007", "9" ] ] }, "page" : "3369-3373", "title" : "Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3", "type" : "article-journal", "volume" : "92" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Farooqi et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Farooqi et al. 2007) and polygenic forms of obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.177", "ISSN" : "1546-1718", "PMID" : "18604207", "abstract" : "Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.", "author" : [ { "dropping-particle" : "", "family" : "Benzinou", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Creemers", "given" : "John W M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choquet", "given" : "Helene", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lobbens", "given" : "Stephane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dina", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guerardel", "given" : "Audrey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boutin", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jouret", "given" : "Beatrice", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heude", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tichet", "given" : "Jean", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Potoczna", "given" : "Natascha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stunff", "given" : "Catherine", "non-dropping-particle" : "Le", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Czernichow", "given" : "Sebastien", "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" : "Borch-Johnsen", "given" : "Knut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Andersen", "given" : "Gitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiess", "given" : "Wieland", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "K\u00f6rner", "given" : "Antje", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kovacs", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobson", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlsson", "given" : "Lena M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walley", "given" : "Andrew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "J\u00f8rgensen", "given" : "Torben", "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" : "Meyre", "given" : "David", "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" : "8", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "943-945", "title" : "Common nonsynonymous variants in PCSK1 confer risk of obesity", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Benzinou et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Benzinou et al. 2008). To the author’s knowledge, this study is the first to find an association between PCSK1 and increased energy consumption. Evidence from the monogenic form of obesity involving PCSK1 supports a hypothetical relationship. In the monogenic form of obesity, a total PCSK1 deficiency causes a prohormone convertase 1/3 deficiency leading to extreme hyperphagia because of an inability to cleave prohormones related to metabolism such as pro-insulin or pro-POMC ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/db11-0305", "ISSN" : "1939-327X", "PMID" : "22210313", "abstract" : "Null mutations in the PCSK1 gene, encoding the proprotein convertase 1/3 (PC1/3), cause recessive monogenic early onset obesity. Frequent coding variants that modestly impair PC1/3 function mildly increase the risk for common obesity. The aim of this study was to determine the contribution of rare functional PCSK1 mutations to obesity. PCSK1 exons were sequenced in 845 nonconsanguineous extremely obese Europeans. Eight novel nonsynonymous PCSK1 mutations were identified, all heterozygous. Seven mutations had a deleterious effect on either the maturation or the enzymatic activity of PC1/3 in cell lines. Of interest, five of these novel mutations, one of the previously described frequent variants (N221D), and the mutation found in an obese mouse model (N222D), affect residues at or near the structural calcium binding site Ca-1. The prevalence of the newly identified mutations was assessed in 6,233 obese and 6,274 lean European adults and children, which showed that carriers of any of these mutations causing partial PCSK1 deficiency had an 8.7-fold higher risk to be obese than wild-type carriers. These results provide the first evidence of an increased risk of obesity in heterozygous carriers of mutations in the PCSK1 gene. Furthermore, mutations causing partial PCSK1 deficiency are present in 0.83% of extreme obesity phenotypes.", "author" : [ { "dropping-particle" : "", "family" : "Creemers", "given" : "John W M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stijnen", "given" : "Pieter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vatin", "given" : "Vincent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pigeyre", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beckers", "given" : "Sigri", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulemans", "given" : "Sandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Than", "given" : "Manuel E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yengo", "given" : "Lo\u00efc", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tauber", "given" : "Maith\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balkau", "given" : "Beverley", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hul", "given" : "Wim", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaal", "given" : "Luc", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pattou", "given" : "Fran\u00e7ois", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Froguel", "given" : "Philippe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "2" ] ] }, "page" : "383-90", "title" : "Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity.", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.ymgme.2013.04.005", "ISBN" : "9566970396143", "ISSN" : "1096-7206", "PMID" : "23800642", "abstract" : "Non-synonymous mutations affecting both alleles of PCSK1 (proprotein convertase 1/3) are associated with obesity and impaired prohormone processing. We report a proband who was compound heterozygous for a maternally inherited frameshift mutation and a paternally inherited 474kb deletion that encompasses PCSK1, representing a novel genetic mechanism underlying this phenotype. Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation.", "author" : [ { "dropping-particle" : "", "family" : "Frank", "given" : "Graeme R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fox", "given" : "Joyce", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Candela", "given" : "Ninfa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jovanovic", "given" : "Zorica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bochukova", "given" : "Elena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Jeremiah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Papenhausen", "given" : "Peter R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Molecular genetics and metabolism", "id" : "ITEM-2", "issue" : "1-2", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "191-4", "publisher" : "The Authors", "title" : "Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency.", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Creemers et al. 2012; Frank et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Creemers et al. 2012; Frank et al. 2013). It is conceivable that other functional variants in PCSK1 could similarly decrease prohormone convertase 1/3 levels, leading to overeating and a milder form of obesity as seen in polygenic forms of obesity. The reduced effect of the functional variants compared to total PCSK1 deficiency may be part of the reason no previous studies have detected a relationship as the effect size is small. Mice models also support the role of prohormone convertase in obesity with a study finding that mice with a novel allele of mouse prohormone convertase (PC1, N222D) experienced increased energy intake and elevated body weight compared to wild type littermates. The mutation is semi-dominant as mice heterozygous for the trait experienced a more mild increase in energy consumption and obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/hmg/ddl111", "ISSN" : "0964-6906", "PMID" : "16644867", "abstract" : "Prohormone convertase 1 (PC1) mutations lead to obesity in humans. However, Pc1 knockout mice do not become obese; in fact, they are runted due to a defect in growth-hormone releasing hormone processing, leading to the speculation that PC1 subserves different functions between mouse and human. Here, we report a novel allele of mouse Pc1 (N222D) that leads to obesity, abnormal proinsulin processing and multiple endocrinological defects. Increased energy intake and a more efficient metabolism contribute to the obesity in Pc1(N222D/N222D) mice. Defective proinsulin processing leads to glucose intolerance, but neither insulin resistance nor diabetes develop despite obesity. The obesity is associated with impaired autocatalytic activation of mature PC1 and reduced hypothalamic alpha-MSH. This is the first characterization of Pc1 mutation in a model organism that mimics human PC1 deficiency.", "author" : [ { "dropping-particle" : "", "family" : "Lloyd", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bohan", "given" : "Sandy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gekakis", "given" : "Nicholas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Human molecular genetics", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2006", "6", "1" ] ] }, "page" : "1884-1893", "title" : "Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Lloyd et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Lloyd et al. 2006). The current evidence associating a genotype score with dietary intake parameters is inconclusive. Both ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/oby.20592", "ISSN" : "1930-739X", "PMID" : "23929626", "abstract" : "OBJECTIVE: Many confirmed genetic loci for obesity are expressed in regions of the brain that regulate energy intake and reward-seeking behavior. Whether these loci contribute to the development of specific eating behaviors has not been investigated. The relationship between a genetic susceptibility to obesity and cognitive restraint, uncontrolled and emotional eating was examined. METHODS: Eating behavior and body mass index (BMI) were determined by questionnaires for 1471 men and 2381 women from two US cohorts. Genotypes were extracted from genome-wide scans and a genetic-risk score (GRS) derived from 32 obesity-loci was calculated. RESULTS: The GRS was positively associated with emotional and uncontrolled eating (P<0.002). In exploratory analysis, BMI-increasing variants of MTCH2, TNNI3K, and ZC3H4 were positively associated with emotional eating and those of TNNI3K and ZC3H4 were positively associated with uncontrolled eating. The BMI-increasing variant of FTO was positively and those of LRP1B and TFAP2B were inversely associated with cognitive restraint. These associations for single SNPs were independent of BMI but were not significant after multiple-testing correction. CONCLUSIONS: An overall genetic susceptibility to obesity may also extend to eating behaviors. The link between specific loci and obesity may be mediated by eating behavior but larger studies are warranted to confirm these results.", "author" : [ { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimm", "given" : "Eric B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curhan", "given" : "Gary C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "135-141", "title" : "Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cornelis et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cornelis et al. 2014) and ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12263-013-0352-8", "ISSN" : "1555-8932", "PMID" : "23861046", "abstract" : "Gene-environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malm\u00f6 Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 \u00d7 10(-34)), fat mass (P = 6.3 \u00d7 10(-28)) and fat-free mass (P = 1.3 \u00d7 10(-24)). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 \u00d7 10(-4)). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet.", "author" : [ { "dropping-particle" : "", "family" : "Rukh", "given" : "Gull", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedblad", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wirf\u00e4lt", "given" : "Elisabet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ericson", "given" : "Ulrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genes & Nutrition", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "7", "17" ] ] }, "page" : "535-547", "title" : "Genetic susceptibility to obesity and diet intakes: association and interaction analyses in the Malm\u00f6 Diet and Cancer Study", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rukh et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rukh et al. 2013) found that a higher genotype risk score is associated with high BMI, however while ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/oby.20592", "ISSN" : "1930-739X", "PMID" : "23929626", "abstract" : "OBJECTIVE: Many confirmed genetic loci for obesity are expressed in regions of the brain that regulate energy intake and reward-seeking behavior. Whether these loci contribute to the development of specific eating behaviors has not been investigated. The relationship between a genetic susceptibility to obesity and cognitive restraint, uncontrolled and emotional eating was examined. METHODS: Eating behavior and body mass index (BMI) were determined by questionnaires for 1471 men and 2381 women from two US cohorts. Genotypes were extracted from genome-wide scans and a genetic-risk score (GRS) derived from 32 obesity-loci was calculated. RESULTS: The GRS was positively associated with emotional and uncontrolled eating (P<0.002). In exploratory analysis, BMI-increasing variants of MTCH2, TNNI3K, and ZC3H4 were positively associated with emotional eating and those of TNNI3K and ZC3H4 were positively associated with uncontrolled eating. The BMI-increasing variant of FTO was positively and those of LRP1B and TFAP2B were inversely associated with cognitive restraint. These associations for single SNPs were independent of BMI but were not significant after multiple-testing correction. CONCLUSIONS: An overall genetic susceptibility to obesity may also extend to eating behaviors. The link between specific loci and obesity may be mediated by eating behavior but larger studies are warranted to confirm these results.", "author" : [ { "dropping-particle" : "", "family" : "Cornelis", "given" : "Marilyn C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rimm", "given" : "Eric B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Curhan", "given" : "Gary C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraft", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "David 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" : "Dam", "given" : "Rob M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2014", "5" ] ] }, "page" : "135-141", "title" : "Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cornelis et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cornelis et al. 2014) found that the genotype risk score had a positive association with emotional and uncontrolled eating, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s12263-013-0352-8", "ISSN" : "1555-8932", "PMID" : "23861046", "abstract" : "Gene-environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malm\u00f6 Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 \u00d7 10(-34)), fat mass (P = 6.3 \u00d7 10(-28)) and fat-free mass (P = 1.3 \u00d7 10(-24)). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 \u00d7 10(-4)). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet.", "author" : [ { "dropping-particle" : "", "family" : "Rukh", "given" : "Gull", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonestedt", "given" : "Emily", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Melander", "given" : "Olle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hedblad", "given" : "Bo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wirf\u00e4lt", "given" : "Elisabet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ericson", "given" : "Ulrika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Orho-Melander", "given" : "Marju", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Genes & Nutrition", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "2013", "7", "17" ] ] }, "page" : "535-547", "title" : "Genetic susceptibility to obesity and diet intakes: association and interaction analyses in the Malm\u00f6 Diet and Cancer Study", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rukh et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rukh et al. 2013) and ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00109-013-1027-z", "ISBN" : "0010901310", "ISSN" : "1432-1440", "PMID" : "23640704", "abstract" : "We investigated the effect of 24 obesity-predisposing single nucleotide polymorphisms (SNPs), separately and in combination, on snacking behavior in three European populations. The 24 SNPs were genotyped in 7,502 subjects (1,868 snackers and 5,634 non-snackers). We tested the hypothesis that obesity risk variants or a genetic risk score increases snacking using a logistic regression adjusted for sex, age, and body mass index. The obesity genetic risk score was not associated with snacking (odds ratio (OR) = 1.00 [0.98-1.02], P value = 0.48). The obesity risk variants of two SNPs (rs925946 and rs7498665) close to the BDNF and SH2B1 genes showed nominal evidence of association with increased snacking (OR = 1.09 [1.01-1.17], P value = 0.0348 and OR = 1.11 [1.04-1.19], P value = 0.00703, respectively) but did not survive Bonferroni corrections for multiple testing. The associations of rs925946 and rs7498665 obesity risk variants with increased BMI (\u03b2 = 0.180 [0.022-0.339], P value = 0.0258 and \u03b2 = 0.166 [0.019-0.313], P value = 0.0271, respectively) were slightly attenuated after adjusting for snacking (\u03b2 = 0.151 [-0.006 to 0.309], P value = 0.0591 and \u03b2 = 0.152 [0.006-0.297], P value = 0.0413). Our data suggest that genetic predisposition to obesity does not significantly contribute to snacking behavior. The nominal associations of rs925946 and rs7498665 obesity risk variants near the BDNF and SH2B1 genes with increased snacking deserve further investigation.", "author" : [ { "dropping-particle" : "", "family" : "Robiou-du-Pont", "given" : "S\u00e9bastien", "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" : "Lobbens", "given" : "St\u00e9phane", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Durand", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horber", "given" : "Fritz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lantieri", "given" : "Olivier", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marre", "given" : "Michel", "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" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Mol Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013", "5", "3" ] ] }, "title" : "Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Robiou-du-Pont et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Robiou-du-Pont et al. 2013) found that an increased risk score was associated with a decrease in energy consumption and had no association with snacking respectively. In our study we found that the genotype score was positively associated with both BMI and total energy consumption. One possible explanation for the discrepancy between studies is that while monogenic forms of obesity are always associated with increased energy consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2174/138920211795677895", "ISSN" : "1875-5488", "PMID" : "22043165", "abstract" : "Candidate gene and genome-wide association studies have led to the discovery of nine loci involved in Mendelian forms of obesity and 58 loci contributing to polygenic obesity. These loci explain a small fraction of the heritability for obesity and many genes remain to be discovered. However, efforts in obesity gene identification greatly modified our understanding of this disorder. In this review, we propose an overlook of major lessons learned from 15 years of research in the field of genetics and obesity. We comment on the existence of the genetic continuum between monogenic and polygenic forms of obesity that pinpoints the role of genes involved in the central regulation of food intake and genetic predisposition to obesity. We explain how the identification of novel obesity predisposing genes has clarified unsuspected biological pathways involved in the control of energy balance that have helped to understand past human history and to explore causality in epidemiology. We provide evidence that obesity predisposing genes interact with the environment and influence the response to treatment relevant to disease prediction.", "author" : [ { "dropping-particle" : "", "family" : "Choquet", "given" : "H\u00e9l\u00e8ne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Genomics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "5" ] ] }, "page" : "169-179", "title" : "Genetics of obesity: What have we Learned?", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Choquet and Meyre 2011a)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Choquet and Meyre 2011a), the association of obesity predisposing SNPs may modulate BMI through other mechanisms than food intake. For example, rs9939609 (FTO) has consistently been shown to interact with high energy or high saturated fat diets to lead to obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2337/dc10-0948", "ISSN" : "1935-5548", "PMID" : "21266646", "abstract" : "Variation in the fat mass and obesity-associated (FTO) gene is associated with obesity. The extent to which separate and combined effects of physical activity and caloric intake modify this association remains unclear.", "author" : [ { "dropping-particle" : "", "family" : "Ahmad", "given" : "Tariq", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "I-Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Par\u00e9", "given" : "Guillaume", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chasman", "given" : "Daniel I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rose", "given" : "Lynda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ridker", "given" : "Paul M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mora", "given" : "Samia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Diabetes Care", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2011", "3" ] ] }, "page" : "675-680", "title" : "Lifestyle interaction with fat mass and obesity-associated (FTO) genotype and risk of obesity in apparently healthy U.S. women.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.3945/jn.111.143826.level", "author" : [ { "dropping-particle" : "", "family" : "Corella", "given" : "Dolores", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Arnett", "given" : "Donna K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tucker", "given" : "Katherine L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kabagambe", "given" : "Edmond K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tsai", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parnell", "given" : "Laurence D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lai", "given" : "Chao-qiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Yu-chi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warodomwichit", "given" : "Daruneewan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hopkins", "given" : "Paul N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Nutr", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "2219-2225", "title" : "A high intake of saturated fatty acids strengthens the association between the fatt mass and and obesity-associated gene and BMI", "type" : "article-journal", "volume" : "141" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1017/S0007114511003424", "ISSN" : "1475-2662", "PMID" : "21798115", "abstract" : "The rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene has been widely associated with childhood obesity in several European cohorts. This association appears to be dependent on dietary macronutrients. Therefore, the aim of the present study was to evaluate whether dietary fatty acid intake distribution could interact with this FTO genetic variation and obesity in a Spanish case-control study of children and adolescents. A total of 354 Spanish children and adolescents aged 6-18 years (49 % males) were genotyped for the rs9939609 variant of the FTO gene. Anthropometric parameters were taken and energy intake was measured. We observed an interaction between the consumption of SFA (percentage of total energy) and PUFA:SFA ratio and obesity risk linked to the rs9939609 SNP of the FTO gene. In the study population of the present study, the risk allele carriers consuming more than 12\u00b76 % SFA (of total energy) had an increased obesity risk compared with TT carriers. In a similar way, A allele carriers with an intake ratio lower than 0\u00b743 PUFA:SFA presented a higher obesity risk than TT subjects. In summary, the present study reports for the first time the influence of dietary fatty acid distribution on the effect of the rs9939609 polymorphism of the FTO gene on children and adolescents' obesity risk.", "author" : [ { "dropping-particle" : "", "family" : "Moleres", "given" : "Adriana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ochoa", "given" : "M Carmen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rendo-Urteaga", "given" : "Tara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez-Gonz\u00e1lez", "given" : "M Angel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Azcona San Juli\u00e1n", "given" : "M Cristina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mart\u00ednez", "given" : "J Alfredo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marti", "given" : "Amelia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Brit J Nutr", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "2" ] ] }, "page" : "533-538", "title" : "Dietary fatty acid distribution modifies obesity risk linked to the rs9939609 polymorphism of the fat mass and obesity-associated gene in a Spanish case-control study of children.", "type" : "article-journal", "volume" : "107" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.3945/jn.111.153460.risk", "author" : [ { "dropping-particle" : "", "family" : "Phillips", "given" : "Catherine M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kesse-Guyot", "given" : "Emmanuelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mcmanus", "given" : "Ross", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hercberg", "given" : "Serge", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lairon", "given" : "Denis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Planells", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roche", "given" : "Helen M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Nutr", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "824-831", "title" : "High dietary saturated fat intake accentuates obesity risk associated with the fatt mas and obesity-associated gene in adults", "type" : "article-journal", "volume" : "142" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Ahmad et al. 2011; Corella et al. 2011; Moleres et al. 2012; Phillips et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Ahmad et al. 2011; Corella et al. 2011; Moleres et al. 2012; Phillips et al. 2012). PPARG which encodes peroxisome proliferator-activated receptor y (PPARy), a nuclear receptor involved in fatty acid sensing and the regulation of adipocyte differentiation, lipid metabolism, fat storage, and insulin sensitivity is associated with obesity and BMI and suggests that lipid metabolism may be an important component of obesity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3109/09540261.2012.685056", "ISSN" : "1369-1627", "PMID" : "22724641", "abstract" : "The prevalence of childhood obesity is increasing in many countries and confers risks for early type 2 diabetes, cardiovascular disease and metabolic syndrome. In the presence of potent 'obesogenic' environments not all children become obese, indicating the presence of susceptibility and resistance. Taking an energy balance approach, susceptibility could be mediated through a failure of appetite regulation leading to increased energy intake or via diminished energy expenditure. Evidence shows that heritability estimates for BMI and body fat are paralleled by similar coefficients for energy intake and preferences for dietary fat. Twin studies implicate weak satiety and enhanced food responsiveness as factors determining an increase in BMI. Single gene mutations, for example in the leptin receptor gene, that lead to extreme obesity appear to operate through appetite regulating mechanisms and the phenotypic response involves overconsumption and a failure to inhibit eating. Investigations of robustly characterized common gene variants of fat mass and obesity associated (FTO), peroxisome proliferator-activated receptor (PPARG) and melanocortin 4 receptor (MC4R) which contribute to variance in BMI also influence the variance in appetite factors such as measured energy intake, satiety responsiveness and the intake of palatable energy-dense food. A review of the evidence suggests that susceptibility to childhood obesity involving specific allelic variants of certain genes is mediated primarily through food consumption (appetite regulation) rather than through a decrease in activity-related energy expenditure. This conclusion has implications for early detection of susceptibility, and for prevention and management of childhood obesity.", "author" : [ { "dropping-particle" : "", "family" : "Cecil", "given" : "Joanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dalton", "given" : "Michelle", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finlayson", "given" : "Graham", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blundell", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hetherington", "given" : "Marion", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International review of psychiatry (Abingdon, England)", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "6" ] ] }, "page" : "200-10", "title" : "Obesity and eating behaviour in children and adolescents: contribution of common gene polymorphisms.", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cecil et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cecil et al. 2012). Various SNPs located in or near MC4R, a gene involved in monogenic forms of obesity, have been found to be associated with basal metabolic rate (rs11872992), respiratory quotient, fat oxidation, total energy expenditure, insulin resistance, and leptin (SNP – 1385), and total activity levels (SNP – 1704) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3945/ajcn.2009.28514.1", "author" : [ { "dropping-particle" : "", "family" : "Cole", "given" : "Shelley A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Butte", "given" : "Nancy F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Voruganti", "given" : "V Saroja", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cai", "given" : "Guowen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haack", "given" : "Karin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Jack W Kent", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blangero", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Comuzzie", "given" : "Anthony G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mcpherson", "given" : "John D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gibbs", "given" : "Richard A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "title" : "Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cole et al. 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cole et al. 2010). Some obesity SNPs likely work through mechanisms other than increased energy consumption. For example olfactomedin 4 (OLFM4) and homebox protein (HOXB5) are associated with common early-onset obesity. OLFM4 plays a role in immunity function against Helicobacter pylori infection with increased weight being associated with more bacteria and homebox protein (HOXB5), coded for by the HOXB5 gene, is proposed to play a role in gut function with transcription factors increasing after fat loss ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ng.2247", "ISSN" : "1546-1718", "PMID" : "22484627", "abstract" : "Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (\u226595th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 \u00d7 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 \u00d7 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 \u00d7 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).", "author" : [ { "dropping-particle" : "", "family" : "Bradfield", "given" : "Jonathan P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taal", "given" : "H Rob", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scherag", "given" : "Andr\u00e9", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lecoeur", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Warrington", "given" : "Nicole M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hypponen", "given" : "Elina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holst", "given" : "Claus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valcarcel", "given" : "Beatriz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thiering", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Salem", "given" : "Rany M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schumacher", "given" : "Fredrick R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cousminer", "given" : "Diana L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sleiman", "given" : "Patrick M a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Jianhua", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berkowitz", "given" : "Robert I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vimaleswaran", "given" : "Karani S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarick", "given" : "Ivonne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pennell", "given" : "Craig E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "David M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "St Pourcain", "given" : "Beate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berry", "given" : "Diane J", "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" : "Hofman", "given" : "Albert", "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" : "Andr\u00e9 G", "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" : "Valk", "given" : "Ralf J P", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jongste", "given" : "Johan C", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Postma", "given" : "Dirkje S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gauderman", "given" : "W James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hassanein", "given" : "Mohamed T", "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" : "Boreham", "given" : "Colin a G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Neville", "given" : "Charlotte E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moreno", "given" : "Luis a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pouta", "given" : "Anneli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hartikainen", "given" : "Anna-Liisa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Li", "given" : "Mingyao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raitakari", "given" : "Olli", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lehtim\u00e4ki", "given" : "Terho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eriksson", "given" : "Johan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palotie", "given" : "Aarno", "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" : "Deloukas", "given" : "Panos", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McMahon", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ring", "given" : "Susan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kemp", "given" : "John P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buxton", "given" : "Jessica L", "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" : "Bustamante", "given" : "Mariona", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guxens", "given" : "M\u00f2nica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hirschhorn", "given" : "Joel N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gillman", "given" : "Matthew W", "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" : "Bisgaard", "given" : "Hans", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gilliland", "given" : "Frank D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heinrich", "given" : "Joachim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wheeler", "given" : "Eleanor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barroso", "given" : "In\u00eas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meirhaeghe", "given" : "Aline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "S\u00f8rensen", "given" : "Thorkild I a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Power", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Lyle J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Widen", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I Sadaf", "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" : "Meyre", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jarvelin", "given" : "Marjo-Riitta", "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" : "Smith", "given" : "George Davey", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hakonarson", "given" : "Hakon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grant", "given" : "Struan F a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nature Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "page" : "526-231", "title" : "A genome-wide association meta-analysis identifies new childhood obesity loci", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Bradfield et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Bradfield et al. 2012). However, there is also substantial evidence that some SNPs, in particular FTO are associated with energy consumption independently of BMI ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Cecil", "given" : "Joanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tavendale", "given" : "Roger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watt", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hetherington", "given" : "Marion M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Palmer", "given" : "Colin N A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "N Engl J Med", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "2558-2566", "title" : "An obesity-associated FTO gene variant and increased energy intake in children", "type" : "article-journal", "volume" : "359" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1055/s-0028-1087176", "ISSN" : "1439-3646", "PMID" : "19053021", "abstract" : "Polymorphisms in the FTO (fat mass- and obesity-associated) gene are associated with obesity. The mechanisms how genetic variation in this gene influences body weight are unknown. Body weight is determined by energy intake/storage and energy expenditure. In this study, we investigated whether genetic variation in FTO influences energy expenditure or food intake in carefully phenotyped subjects. In 380 German subjects, insulin sensitivity was measured by a hyperinsulinemic euglycemic clamp. Lean body mass and body fat were quantified using the bioimpedance method. Indirect calorimetry was used to estimate the metabolic rate. Food intake was assessed using food diaries (mean 11+/-1 d) in 151 subjects participating in a lifestyle intervention program to prevent diabetes. All subjects were genotyped for the FTO single nucleotide polymorphism (SNP) rs8050136. The risk allele of SNP rs8050136 was associated with higher body fat-related parameters (all p< or =0.04, additive inheritance model). Energy expenditure was not affected by the SNP. However, the risk allele of rs8050136 was significantly associated with higher energy intake (p=0.01, dominant inheritance model) during dietary restriction. Our data suggest that the increased body weight in carriers of the risk allele of FTO SNP rs8050136 is a consequence of increased food intake, but not of impaired energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Haupt", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thamer", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Staiger", "given" : "H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tschritter", "given" : "O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kirchhoff", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Machicao", "given" : "F", "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" : "Stefan", "given" : "N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fritsche", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Exp Clin Endocrinol Diabetes", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2009", "4" ] ] }, "page" : "194-197", "title" : "Variation in the FTO gene influences food intake but not energy expenditure", "type" : "article-journal", "volume" : "117" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1038/oby.2008.318", "ISSN" : "1930-7381", "PMID" : "18551109", "abstract" : "The FTO gene has significant polymorphic variation associated with obesity, but its function is unknown. We screened a population of 150 whites (103F/47M) resident in NE Scotland, United Kingdom, for variants of the FTO gene and linked these to phenotypic variation in their energy expenditure (basal metabolic rate (BMR) and maximal oxygen consumption VO(2)max) and energy intake. There was no significant association between the FTO genotype and BMR or VO(2)max. The FTO genotype was significantly associated (P = 0.024) with variation in energy intake, with average daily intake being 9.0 MJ for the wild-type TT genotype and 10.2 and 9.5 MJ for the \"at risk\" AT and AA genotypes, respectively. Adjusting intake for BMR did not remove the significance (P = 0.043). FTO genotype probably affects obesity via effects on food intake rather than energy expenditure.", "author" : [ { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rance", "given" : "Kellie a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnstone", "given" : "Alexandra M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2008", "8" ] ] }, "page" : "1961-1965", "title" : "Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "ISSN" : "1938-3207", "PMID" : "18842783", "abstract" : "BACKGROUND: A region of chromosome 16 containing the fat mass-and obesity-associated gene (FTO) is reproducibly associated with fat mass and body mass index (BMI), risk of obesity, and adiposity. OBJECTIVES: We aimed to assess the possibility that appetite plays a role in the association between FTO and BMI. DESIGN: Detailed dietary report information from the Avon Longitudinal Study of Parents and Children allowed the exploration of relations between FTO variation and dietary intake. Analyses were performed to investigate possible associations between variation at the FTO locus and the intake of a range of micronutrients and macronutrients, with adjustment for the bias often found within dietary report data when factors related to BMI are assessed. To test the hypothesis that FTO may be influencing appetite directly, rather than indirectly via BMI and altered intake requirements, we also assessed associations between FTO and dietary intake independent of BMI. RESULTS: Relations between a single-nucleotide polymorphism characterizing the FTO signal (rs9939609) and dietary variables were found and can be summarized by the effect of each additional allele (per-allele effects) on total energy and total fat (P < 0.001 for both). These associations were attenuated, but they persisted specifically for fat and energy consumption after adjustment for BMI [total daily fat consumption: approximately 1.5 g/d (P = 0.02 for the per-allele difference); total daily energy consumption: approximately 25 kJ/d (P = 0.03 for the per-allele difference)]. CONCLUSION: These associations suggest that persons carrying minor variants at rs9939609 were consuming more fat and total energy than were those not carrying such variants. They also suggest that this difference was not simply dependent on having higher average BMIs among the former group.", "author" : [ { "dropping-particle" : "", "family" : "Timpson", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emmett", "given" : "Pauline 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" : "Rogers", "given" : "Imogen", "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" : "Davey Smith", "given" : "George", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Am J Clin Nutr", "id" : "ITEM-4", "issue" : "4", "issued" : { "date-parts" : [ [ "2008", "10" ] ] }, "page" : "971-978", "title" : "The fat mass- and obesity-associated locus and dietary intake in children", "type" : "article-journal", "volume" : "88" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Cecil et al. 2008; Speakman et al. 2008; Timpson et al. 2008; Haupt et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Cecil et al. 2008; Speakman et al. 2008; Timpson et al. 2008; Haupt et al. 2009). Our study found an association between rs1401635 (BDFN), rs1401625 (PCSK1) and the genotype score and total energy consumption supporting the view that obesity predisposing SNPs are causally involved in the regulation of energy intake. Currently, excessive energy intake is considered the primary risk factor for obesity, far more so than decreased physical activity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1242/dmm.010553", "ISSN" : "1754-8411", "PMID" : "22915015", "abstract" : "Work on obesity is evolving, and obesity is a consequence of our evolutionary history. In the space of 50 years, we have become an obese species. The reasons why can be addressed at a number of different levels. These include separating between whether the primary cause lies on the food intake or energy expenditure side of the energy balance equation, and determining how genetic and environmental effects contribute to weight variation between individuals. Opinion on whether increased food intake or decreased energy expenditure drives the obesity epidemic is still divided, but recent evidence favours the idea that food intake, rather than altered expenditure, is most important. There is more of a consensus that genetics explains most (probably around 65%) of weight variation between individuals. Recent advances in genome-wide association studies have identified many polymorphisms that are linked to obesity, yet much of the genetic variance remains unexplained. Finding the causes of this unexplained variation will be an impetus of genetic and epigenetic research on obesity over the next decade. Many environmental factors - including gut microbiota, stress and endocrine disruptors - have been linked to the risk of developing obesity. A better understanding of gene-by-environment interactions will also be key to understanding obesity in the years to come.", "author" : [ { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Disease models & mechanisms", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2012", "9" ] ] }, "page" : "569-73", "title" : "Fat: an evolving issue.", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Speakman and O\u2019Rahilly 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Speakman and O’Rahilly 2012). People who are genetically predisposed to obesity, either from rare and severe monogenic forms or from common polygenic variants with an accumulation of variants with individual modest effect on disease risk, are much more vulnerable to the effects of the “obesogenic” environment in which food is inexpensive, abundant, served in large portions, and heavily marketed ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.psc.2011.08.005", "ISSN" : "1558-3147", "PMID" : "22098799", "abstract" : "The obesity epidemic in the United States has proven difficult to reverse. We have not been successful in helping people sustain the eating and physical activity patterns that are needed to maintain a healthy body weight. There is growing recognition that we will not be able to sustain healthy lifestyles until we are able to address the environment and culture that currently support unhealthy lifestyles. Addressing obesity requires an understanding of energy balance. From an energy balance approach it should be easier to prevent obesity than to reverse it. Further, from an energy balance point of view, it may not be possible to solve the problem by focusing on food alone. Currently, energy requirements of much of the population may be below the level of energy intake than can reasonably be maintained over time. Many initiatives are underway to revise how we build our communities, the ways we produce and market our foods, and the ways we inadvertently promote sedentary behavior. Efforts are underway to prevent obesity in schools, worksites, and communities. It is probably too early to evaluate these efforts, but there have been no large-scale successes in preventing obesity to date. There is reason to be optimistic about dealing with obesity. We have successfully addressed many previous threats to public health. It was probably inconceivable in the 1950s to think that major public health initiatives could have such a dramatic effect on reducing the prevalence of smoking in the United States. Yet, this serious problem was addressed via a combination of strategies involving public health, economics, political advocacy, behavioral change, and environmental change. Similarly, Americans have been persuaded to use seat belts and recycle, addressing two other challenges to public health. But, there is also reason to be pessimistic. Certainly, we can learn from our previous efforts for social change, but we must realize that our challenge with obesity may be greater. In the other examples cited, we had clear goals in mind. Our goals were to stop smoking, increase the use of seatbelts, and increase recycling. The difficulty of achieving these goals should not be minimized, but they were clear and simple goals. In the case of obesity, there is no clear agreement about goals. Moreover, experts do not agree on which strategies should be implemented on a widespread basis to achieve the behavioral changes in the population needed to reverse the high prevalence rates o\u2026", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Nia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Catenacci", "given" : "Victoria a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wyatt", "given" : "Holly R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "James O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Psychiatric Clinics of North America", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "717-732", "publisher" : "Elsevier Inc.", "title" : "Obesity: overview of an epidemic", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Mitchell et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Mitchell et al. 2011). With the knowledge from this study and previous research, we can conclude that because many people are genetically predisposed to obesity and certain negative food consumption patterns, changes to the accessibility and quality of the food available are required which can be accomplished through changes to policy. Strengths of our study included using a FFQ validated for total energy intake, macronutrients, and three of the four subcomponents of fat we investigated in the study. An ethnically homogenous sample while decreasing the generalizability of our findings, decreases the risk that the FFQ would less accurately estimate food consumption for certain ethnicities and helps to control for culturally specific habits that may relate to obesity. Though a modest sample size limited the statistical power for the study, our nominally significant results are well supported by either prior research or additional biological evidence, decreasing the likelihood that results are spurious ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ije/dym159", "ISSN" : "1464-3685", "PMID" : "17898028", "abstract" : "Established guidelines for causal inference in epidemiological studies may be inappropriate for genetic associations. A consensus process was used to develop guidance criteria for assessing cumulative epidemiologic evidence in genetic associations. A proposed semi-quantitative index assigns three levels for the amount of evidence, extent of replication, and protection from bias, and also generates a composite assessment of 'strong', 'moderate' or 'weak' epidemiological credibility. In addition, we discuss how additional input and guidance can be derived from biological data. Future empirical research and consensus development are needed to develop an integrated model for combining epidemiological and biological evidence in the rapidly evolving field of investigation of genetic factors.", "author" : [ { "dropping-particle" : "", "family" : "Ioannidis", "given" : "John P a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boffetta", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Little", "given" : "Julian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "O'Brien", "given" : "Thomas R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Uitterlinden", "given" : "Andre G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vineis", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Balding", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chokkalingam", "given" : "Anand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dolan", "given" : "Siobhan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flanders", "given" : "W Dana", "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" : "McCarthy", "given" : "Mark I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McDermott", "given" : "David H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Page", "given" : "Grier P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rebbeck", "given" : "Timothy R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seminara", "given" : "Daniela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khoury", "given" : "Muin J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of epidemiology", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2008", "2" ] ] }, "page" : "120-32", "title" : "Assessment of cumulative evidence on genetic associations: interim guidelines.", "type" : "article-journal", "volume" : "37" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Ioannidis et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Ioannidis et al. 2008). Additionally, the use of a genotype score is relatively novel. Limitations of this study include using a cross-sectional sample which does not allow for the temporal relationship between energy intake and obesity to be examined in the context of obesity predisposing SNPs, the use of FFQ data opposed to ad libitum tests or dietary recall methods which decreases the accuracy of the food parameter estimates, and the need for some of the novel nominally significant results to be replicated. 4.5 ConclusionsIn conclusion, our study showed nominally significant associations of rs9939609 (FTO) and rs1514176 (TNN13K), and genotype score with BMI, an association of six of the 14 SNPs and the genotype score with dietary intake parameters. The associations of BDNF (rs6265 and rs1401635), with total fat, MUFA, and PUFA intake with rs1401635 also being associated with total energy and trans-fat intake and rs6235 (PCSK1) and the genotype score and total energy intake in particular warrant further investigation. Our data supports the view that the genetic predisposition of obesity includes some obesity SNPs influencing energy consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2008.239", "ISSN" : "1476-5497", "PMID" : "19136992", "abstract" : "In the spirit of celebration associated with the 20th anniversary of the Pennington Biomedical Research Center, we have seized the opportunity of taking a highly personal and not at all comprehensive 'whistle-stop tour' of a large body of evidence that, we feel, supports the following conclusions: (1) that body fat stores are regulated by biological control processes in humans as they are in lower animals; (2) that there are major inherited influences on the efficiency whereby such control processes operate in humans; (3) that the precise nature of those genetic and biological influences and how they interact with environmental factors are beginning to be understood; (4) that most of the genes discovered thus far have their principal impact on hunger, satiety and food intake; (5) that while there is understandable resistance to the notion that genes can influence a human behavior such as the habitual ingestion of food, the implications of these discoveries are essentially benign. Indeed, we hope that they may eventually lead to improved treatment for patients and, in addition, help to inculcate a more enlightened attitude to the obese with a reduction in their experience of social and economic discrimination.", "author" : [ { "dropping-particle" : "", "family" : "O'Rahilly", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Farooqi", "given" : "I S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International journal of obesity (2005)", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2008", "12" ] ] }, "page" : "S55-61", "title" : "Human obesity as a heritable disorder of the central control of energy balance.", "type" : "article-journal", "volume" : "32 Suppl 7" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(O\u2019Rahilly and Farooqi 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(O’Rahilly and Farooqi 2008). 5.0 An Evolutionary Perspective on Eating Disorders 5.1 Introduction There is an ongoing debate about the causes of eating disorders. It is clear that there is a complex interplay between life experiences, personal characteristics/environmental factors, and genetics. The life experiences that are associated with eating disorders, such as early menarche (BN), high parental expectations, sexual abuse, family dieting, criticism about one’s shape and size, and participation in activities promoting a low fat mass like distance running, swimming, dancing, and modelling ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/0954026031000136839", "ISSN" : "0954-0261", "PMID" : "15276960", "abstract" : "Eating disorders rank among the most debilitating psychiatric disturbances that affect young women. Knowledge has increased in recent years about the two major eating disorders, anorexia nervosa (AN) and bulimia nervosa (BN); however, much remains unknown. This review article will provide an overview of the epidemiology, proposed risk factors and clinical features of AN, and BN, as well as current recommendations for evaluation and treatment of these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Klein", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Review of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003", "8" ] ] }, "page" : "205-216", "title" : "Eating disorders", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Klein and Walsh 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Klein and Walsh 2003) are well established. In addition to life experiences, personal characteristics and environmental factors such as gender, age, birth cohort, ethnicity, and culture are likely important contributors to the development of eating disorders. Despite the high hereditability of eating disorders, estimated to be between 0.28 and 0.76 for AN, 0.30 to 0.83 for BN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1375/183242705774310114", "ISSN" : "1832-4274", "PMID" : "16212836", "abstract" : "Substantial effort has been put into the exploration of the biological background of eating disorders, through family, twin and molecular genetic studies. Family studies have shown that anorexia (AN) and bulimia nervosa (BN) are strongly familial, and that familial etiologic factors appear to be shared by both disorders. Twin studies often focus on broader phenotypes or subthreshold eating disorders. These studies consistently yielded moderate to substantial heritabilities. In addition, there has been a proliferation of molecular genetic studies that focused on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) AN and BN. Seven linkage regions have been identified in genome-wide screens. Many genetic association studies have been performed, but no consistent association between a candidate gene and AN or BN has been reported. Larger genetic association studies and collaborations are needed to examine the involvement of several candidate genes and biological pathways in eating disorders. In addition, twin studies should be designed to assist the molecular work by further exploring genetic determinants of endophenotypes, evaluating the magnitude of contribution to liability of measured genotypes as well as environmental risk factors related to eating disorders. In this manner twin and molecular studies can move the field forward in a mutually informative way.", "author" : [ { "dropping-particle" : "", "family" : "Slof-Op 't Landt", "given" : "Margarita C T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meulenbelt", "given" : "Ingrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Slagboom", "given" : "P Eline", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartels", "given" : "Meike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boomsma", "given" : "Dorret I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Twin Research and Human Genetics", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2005", "10" ] ] }, "page" : "467-482", "title" : "Eating disorders: from twin studies to candidate genes and beyond", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Slof-Op \u2019t Landt et al. 2005)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Slof-Op ’t Landt et al. 2005), and 0.41 to 0.57 for BED ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/7854", "author" : [ { "dropping-particle" : "", "family" : "Thornton", "given" : "Laura M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mazzeo", "given" : "Suzanne E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Topics in Behavioral Neuroscience", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "141-156", "title" : "The heritability of eating disorders: Methods and current findings", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Thornton et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Thornton et al. 2011), there is very limited evidence of robust association between eating disorders and candidate genes or associations detected through GWAS. The high heritability of eating disorders as well as their relatively high prevalence, at least in Western societies, indicate that eating disorders, or behaviours affiliated with eating disorders, may have previously provided an evolutionary advantage. Using personal characteristics and environmental factors which have been identified as risk factors for eating disorders, different evolutionary theories are investigated. 5.2 Suppression of reproduction and sexual competition Some believe that AN is a method through which females can either supress or delay reproduction to avoid procreating at a time when their offspring will have threatened survival. This would ultimately be an advantage as females who supressed reproduction until more favourable environmental conditions would likely have higher lifetime reproductive success therefore would be more likely to pass on the genes responsible for AN characteristics. The theory also states that through social stress, females can try to supress the reproduction of other females in an attempt to increase the chance of finding a high quality mate and create a better environment for their offspring ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0033-5770", "PMID" : "6686686", "abstract" : "Female mammals experience a very high and often unappreciated rate of reproductive failure. Among human pregnancies alone, over 50 per cent fail between conception and parturition, and the majority of these failures are unexplained. These findings present important problems for evolutionary theory as well as for health care practices. This paper addresses these high rates of reproductive failure among mammals, by extending the work of a number of evolutionary biologists regarding the reproductive consequences of environmental adversity. The basic model upon which we elaborate, termed the Reproductive Suppression Model, argues that females can optimize their lifetime reproductive success by suppressing reproduction when future conditions for the survival of offspring are likely to be sufficiently better than present ones as to exceed the costs of the suppression itself. These costs are a function of reproductive time lost and the direct phenotypic effects of the suppression itself. To evaluate the benefits and costs of suppression, the following types of cues should be assessed: the female's physical and mental health, her stage of reproduction, the physical and genetic status of her offspring, and the external conditions at the time of birth. We also examine various issues of social suppression, whereby the conditions for survival of offspring are a function of the reproduction and support of other group members. Under such conditions, some females may be able to improve current conditions for reproduction by suppressing the reproduction of others. Field data from our own work are presented, describing socially mediated reproductive competition among continuously breeding female yellow baboons and among female hoary marmots. Social suppression in other mammals is also evaluated, including that in human beings, and we conclude with some implications of the Reproductive Suppression Model for sexual selection theory regarding female-female reproductive competition, as well as human health care.", "author" : [ { "dropping-particle" : "", "family" : "Wasser", "given" : "S K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barash", "given" : "D P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Quarterly Review of Biology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "1983", "12" ] ] }, "page" : "513-538", "title" : "Reproductive suppression among female mammals: implications for biomedicine and sexual selection theory", "type" : "article-journal", "volume" : "58" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wasser and Barash 1983)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wasser and Barash 1983). While it may be advantageous for dominant females to supress the reproductive capacity of others, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/erv.718", "ISSN" : "1099-0968", "PMID" : "17676667", "abstract" : "Anorexia nervosa (AN) has proven difficult to explain and is especially so from an evolutionary perspective. It is widespread, has probably existed for centuries and includes a genetic component but leads to starvation, infertility and sometimes death. An attempt to explain AN will be made using a synthesis of evolutionary ideas about responses to threat. Dietary restriction is described as a response to perceived threats of exclusion from the group, which would once have been dangerous. This can develop into AN only where the weight loss sets off an ancient adaptive response to the threat of famine. Eating again and weight gain would mean re-entering the competition for status and belonging and are therefore felt as threatening. This synthesis can explain the unusual mix of features found in AN that are otherwise resistant to explanation.", "author" : [ { "dropping-particle" : "", "family" : "Gatward", "given" : "Nicholas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Eating Disorders Review", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "1" ] ] }, "page" : "1-12", "title" : "Anorexia nervosa: an evolutionary puzzle", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Gatward (2007)", "previouslyFormattedCitation" : "(Gatward 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Gatward (2007) proposes that it may also be in the best interest of subordinate females to supress their reproduction through restricting food access. Historically, being accepted as part of a group was critical for survival. While weight loss could be used to become more attractive, severe weight loss such as with AN could be interpreted as a sign of subordination and the potential lack of fertility would remove the subordinate female as a threat to the dominant female. If the subordinate female poses no threat to the dominant female, there is no reason for her to be excluded from the group. Another element of suppression of reproduction is in young girls who have not yet reached sexual maturity. Maintaining a lower weight may delay menarche allowing them to pursue other activities such as academics in modern times before having children ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Surbey", "given" : "M K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ethology and Sociobiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1987" ] ] }, "page" : "47-61", "title" : "Anorexia nervosa, amenorrhea, and adaptation", "type" : "article-journal", "volume" : "8" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Surbey 1987)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Surbey 1987). The theories involving suppression of reproduction are limited however, because they do not explain the hyperactivity seen in AN patients, the denial of the seriousness of their disease and distorted body image, or the presence of AN in males ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Kardum", "given" : "Igor", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gra", "given" : "Asmir", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hudek-Kne\u017eevi", "given" : "Jasna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Topics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "247-263", "title" : "Evolutionary explanations of eating disorders", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kardum et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kardum et al. 2008). A theory of inter-female competition excluding the concept of purposeful suppressed reproduction has also been developed ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Abed", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Medical Psychology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "525-547", "title" : "The sexual competition hypothesis for eating disorders", "type" : "article-journal", "volume" : "71" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Abed 1998)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Abed 1998). The hypothesis states that from an evolutionary perspective, the ability to restrict food access may have been beneficial for females in order to attract potential partners. A “nubile” shape consisting of a low waist to hip ratio is a sign of reproductive potential because it indicates youthfulness as well as no current pregnancy. Being more attractive would increase a female’s likelihood of obtaining and maintaining a high quality partner, therefore providing an advantage to her offspring explaining the high heritability of eating disorders. This theory translates well into modern times where females have been delaying having children until later in life, therefore females may decrease their weight in order to stay competitive with younger females. However, despite the potential for the prevalence of eating disorders to be increasing over time ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-2", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek and van Hoeken 2003; Preti et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek and van Hoeken 2003; Preti et al. 2009), the disease still predominantly affects young females with an peak in incidence between 10 to 19 years ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "Van", "family" : "Son", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartelds", "given" : "Aad I M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "565-569", "title" : "Time trends in the incidence of eating disorders: A primary care study in the Netherlands", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek and van Hoeken 2003; Currin et al. 2005; Son et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek and van Hoeken 2003; Currin et al. 2005; Son et al. 2006) which is not the demographic hypothesized to be trying to lose weight to compete with younger females. As with the suppression of reproductive potential theories, there are limitations to the hypothesis including a lack of applicability to males, the potentially incorrect assumption that a thin body type was/is universally desirable, and that the theory was developed in the context of modern observations. The suppression of reproduction theory and the sexual competition theory are also contradictory. The suppression of reproduction theory indicates that anorectic tendencies decrease fertility while the sexual competition theory indicates that anorectic tendencies will increase the quality of mate and subsequent offspring and not have a negative consequence on fertility. 5.3 Adapted to flee famine hypothesis and rogue hibernation The adapted to flee famine hypothesis (AFFH) provides an explanation for a possible adaptive advantage to what are now known as symptoms of AN. It proposes that food restricting behaviour, hyperactivity, and denial of seriousness of weight loss previously enabled migration during periods of local food insecurity. These characteristics would allow individuals to ignore their near starvation state and continue to be physically active until reaching a more food secure area. These adaptive mechanisms would be positively selected for as only those capable of reaching food secure areas would be able to survive and reproduce, explaining the high heritability of eating disorders ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-295X.110.4.745", "ISSN" : "0033-295X", "PMID" : "14599241", "abstract" : "Anorexia nervosa (AN) is commonly attributed to psychological conflicts, attempts to be fashionably slender, neuroendocrine dysfunction, or some combination of these factors. Considerable research reveals these theories to be incomplete. Psychological and societal factors account for the decision to diet but not for the phenomenology of the disorder; theories of biological defects fail to explain neuroendocrine findings that suggest coordinated physiological mechanisms. This article presents evidence that AN's distinctive symptoms of restricting food, denial of starvation, and hyperactivity are likely to be evolved adaptive mechanisms that facilitated ancestral nomadic foragers leaving depleted environments; genetically susceptible individuals who lose too much weight may trigger these archaic adaptations. This hypothesis accounts for the occurrence of AN-like syndromes in both humans and animals and is consistent with changes observed in the physiology, cognitions, and behavior of patients with AN.", "author" : [ { "dropping-particle" : "", "family" : "Guisinger", "given" : "Shan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Review", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "10" ] ] }, "page" : "745-761", "title" : "Adapted to flee famine: adding an evolutionary perspective on anorexia nervosa", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Guisinger 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Guisinger 2003). Elaborating upon this theory, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.mehy.2013.12.003", "ISSN" : "1532-2777", "PMID" : "24373562", "abstract" : "Anorexia nervosa is a puzzling and often tragic disorder which causes the individual to self starve and hyper-exercise. We present a speculative analysis of the disorder which begins by acknowledging and accepting the adaptation to flee famine theory. This theory holds that anorexia nervosa results from activation of an archaic pathway that functioned well during human's nomadic past. We advance this idea by suggesting that the faulty signal indicating there is a famine, arises from misalignment of the circadian/circannual oscillations. Entry and exit from hibernation is dependent on these cycles, and we draw an analogy between hibernation and anorexia nervosa. We offer ideas for testing the hypothesis, and targeting these faulty signals.", "author" : [ { "dropping-particle" : "", "family" : "Scolnick", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mostofsky", "given" : "David I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Hypotheses", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2" ] ] }, "page" : "231-235", "publisher" : "Elsevier Ltd", "title" : "Anorexia nervosa: A rogue hibernation?", "type" : "article-journal", "volume" : "82" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Scolnick and Mostofsky (2014)", "previouslyFormattedCitation" : "(Scolnick and Mostofsky 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Scolnick and Mostofsky (2014) propose that in today’s food abundant environment, people with AN are trapped in a state of semi-starvation, hypothermia, and hyperactivity because their metabolic pathways are falsely signaling that they are in a food scare environment. This is based upon the metabolic similarities between AN and another physiological adaptation to food scarcity, mammalian hibernation. Mammalian hibernation involves a decreased metabolic rate, hypothermia, and a switch in the metabolic fuel supply from carbohydrates to lipids and ketones. Hibernation allows the animal to survive cold, nutrient depleted winters. The cycle of weight accumulation pre-hibernation, weight loss during hibernation, and subsequent weight gain in spring after hibernation mimic periods of binging and purging in AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.mehy.2013.12.003", "ISSN" : "1532-2777", "PMID" : "24373562", "abstract" : "Anorexia nervosa is a puzzling and often tragic disorder which causes the individual to self starve and hyper-exercise. We present a speculative analysis of the disorder which begins by acknowledging and accepting the adaptation to flee famine theory. This theory holds that anorexia nervosa results from activation of an archaic pathway that functioned well during human's nomadic past. We advance this idea by suggesting that the faulty signal indicating there is a famine, arises from misalignment of the circadian/circannual oscillations. Entry and exit from hibernation is dependent on these cycles, and we draw an analogy between hibernation and anorexia nervosa. We offer ideas for testing the hypothesis, and targeting these faulty signals.", "author" : [ { "dropping-particle" : "", "family" : "Scolnick", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mostofsky", "given" : "David I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Hypotheses", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2" ] ] }, "page" : "231-235", "publisher" : "Elsevier Ltd", "title" : "Anorexia nervosa: A rogue hibernation?", "type" : "article-journal", "volume" : "82" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Scolnick and Mostofsky 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Scolnick and Mostofsky 2014). For both the AFFH and rogue hibernation theories of AN, it is proposed that in modern food secure environments, the traits of restricting food consumption, hyperactivity, and denial of seriousness of weight loss can be turned on by dieting or other contextual reasons for decreasing food consumption ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-295X.110.4.745", "ISSN" : "0033-295X", "PMID" : "14599241", "abstract" : "Anorexia nervosa (AN) is commonly attributed to psychological conflicts, attempts to be fashionably slender, neuroendocrine dysfunction, or some combination of these factors. Considerable research reveals these theories to be incomplete. Psychological and societal factors account for the decision to diet but not for the phenomenology of the disorder; theories of biological defects fail to explain neuroendocrine findings that suggest coordinated physiological mechanisms. This article presents evidence that AN's distinctive symptoms of restricting food, denial of starvation, and hyperactivity are likely to be evolved adaptive mechanisms that facilitated ancestral nomadic foragers leaving depleted environments; genetically susceptible individuals who lose too much weight may trigger these archaic adaptations. This hypothesis accounts for the occurrence of AN-like syndromes in both humans and animals and is consistent with changes observed in the physiology, cognitions, and behavior of patients with AN.", "author" : [ { "dropping-particle" : "", "family" : "Guisinger", "given" : "Shan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Review", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "10" ] ] }, "page" : "745-761", "title" : "Adapted to flee famine: adding an evolutionary perspective on anorexia nervosa", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mehy.2013.12.003", "ISSN" : "1532-2777", "PMID" : "24373562", "abstract" : "Anorexia nervosa is a puzzling and often tragic disorder which causes the individual to self starve and hyper-exercise. We present a speculative analysis of the disorder which begins by acknowledging and accepting the adaptation to flee famine theory. This theory holds that anorexia nervosa results from activation of an archaic pathway that functioned well during human's nomadic past. We advance this idea by suggesting that the faulty signal indicating there is a famine, arises from misalignment of the circadian/circannual oscillations. Entry and exit from hibernation is dependent on these cycles, and we draw an analogy between hibernation and anorexia nervosa. We offer ideas for testing the hypothesis, and targeting these faulty signals.", "author" : [ { "dropping-particle" : "", "family" : "Scolnick", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mostofsky", "given" : "David I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Hypotheses", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2" ] ] }, "page" : "231-235", "publisher" : "Elsevier Ltd", "title" : "Anorexia nervosa: A rogue hibernation?", "type" : "article-journal", "volume" : "82" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Guisinger 2003; Scolnick and Mostofsky 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Guisinger 2003; Scolnick and Mostofsky 2014). The idea that motivations other than the sole intention to lose weight can initiate AN may be important to consider in an international context. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Keel and Klump (2003)", "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Keel and Klump (2003) determined that if weight concerns were removed as diagnostic criteria for AN, the prevalence would be similar in Western and non-Western countries.Both of these theories are supported by epidemiological information on AN. For example the peak incidence of AN is between the years of 10 and 19 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "Van", "family" : "Son", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bartelds", "given" : "Aad I M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "Van", "family" : "Furth", "given" : "Eric F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "565-569", "title" : "Time trends in the incidence of eating disorders: A primary care study in the Netherlands", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek and van Hoeken 2003; Currin et al. 2005; Son et al. 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek and van Hoeken 2003; Currin et al. 2005; Son et al. 2006). Fertility declines as age increases ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/humupd/dms043", "ISSN" : "1460-2369", "PMID" : "23103636", "abstract" : "BACKGROUND Advanced maternal age is associated with reduced fertility and adverse pregnancy outcomes. This review details recent developments in our understanding of the biology and mechanisms underlying reproductive ageing in women and the implications for fertility and pregnancy. METHODS Sociological online libraries (IBSS, SocINDEX), PubMed and Google Scholar were searched for relevant demographic, epidemiological, clinical and biological studies, using key words and hierarchical MeSH terms. From this, we identified and focused on key topics where it was judged that there had been clinically relevant advances in the understanding of ovarian and uterine ageing with implications for improved diagnostics and novel interventions. RESULTS Mapping of the ovarian reserve, follicular dynamics and associated biomarkers, across the reproductive lifespan has recently been performed. This now allows an assessment of the effects of environmental, lifestyle and prenatal exposures on follicular dynamics and the identification of their impact during periods of germ cell vulnerability and may also facilitate early identification of individuals with shorter reproductive lifespans. If women choose to time their family based on their ovarian reserve this would redefine the meaning of family planning. Despite recent reports of the potential existence of stem cells which may be used to restore the primordial follicle and thereby the oocyte pool, therapeutic interventions in female reproductive ageing at present remain limited. Maternal ageing has detrimental effects on decidual and placental development, which may be related to repeated exposure to sex steroids and underlie the association of ageing with adverse perinatal outcomes. CONCLUSIONS Ageing has incontrovertible detrimental effects on the ovary and the uterus. Our enhanced understanding of ovarian ageing will facilitate early identification of individuals at greatest risk, and novel therapeutic interventions. Changes in both ovary and uterus are in addition to age-related co-morbidities, which together have synergistic effects on reducing the probability of a successful pregnancy outcome.", "author" : [ { "dropping-particle" : "", "family" : "Nelson", "given" : "S M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Telfer", "given" : "E E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Anderson", "given" : "R a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Human Reproduction Update", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "67-83", "title" : "The ageing ovary and uterus: new biological insights", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Nelson et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Nelson et al. 2013) therefore it would be most advantageous for young females capable of bearing children in the future to be able to relocate during times of food insecurity. Similarly, AN is mostly found in females with a ratio of 10 to 20 females diagnosed for each male ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.maturitas.2013.04.014", "ISSN" : "1873-4111", "PMID" : "23706279", "abstract" : "Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.", "author" : [ { "dropping-particle" : "", "family" : "Meczekalski", "given" : "Blazej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Podfigurna-Stopa", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulski", "given" : "Krzysztof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "7" ] ] }, "page" : "215-220", "publisher" : "Elsevier Ireland Ltd", "title" : "Long-term consequences of anorexia nervosa", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-4", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/eat.parative", "author" : [ { "dropping-particle" : "", "family" : "Marques", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chih-nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chosak", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belo Diniz", "given" : "Juliana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "412-420", "title" : "Comparative prevalence, correlates of impairment, and service utilization for eating disorders across U.S. ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.appet.2013.01.005", "ISSN" : "1095-8304", "PMID" : "23348361", "abstract" : "During the last 25 years, the careful examination of the eating behavior of individuals with eating disorders has provided critical insights into the nature of these disorders. Crucially, studies investigating components of different eating behaviors have documented that Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED) are characterized by objective disturbances in eating patterns that are significantly different than behaviors exhibited by individuals who do not have these eating disorders. The detailed description of the disturbances in eating behavior has helped to identify diagnostic criteria associated with each disorder, and has led to important hypotheses about the underlying pathophysiology. These advances in understanding have provided, and continue to provide, a foundation for translational research and for the development of novel treatment interventions. This review is based on a presentation given by B. Timothy Walsh, M.D. at the 40th anniversary symposium of the Columbia University Appetite talks outlining the evolution of the discovery of the characteristic eating disturbances seen with each disorder.", "author" : [ { "dropping-particle" : "", "family" : "Heaner", "given" : "Martica K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Appetite", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "185-188", "publisher" : "Elsevier Ltd", "title" : "A history of the identification of the characteristics eating disturbances of bulimia nervosa, binge eating disorders and anorexia nervosa", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-7", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-8", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-10", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Favaro et al. 2003; Hoek and van Hoeken 2003; Currin et al. 2005; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Favaro et al. 2003; Hoek and van Hoeken 2003; Currin et al. 2005; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013). A far greater number of females would be required to re-establish a society compared to males as female’s capacity to reproduce is comparatively far lower. In our review of the ethnic and cultural differences in the prevalence of eating disorders we concluded that differences in prevalence of AN in different ethnicities likely have a strong cultural component, but that there is the possibility that underlying genetic differences between ethnicities may also be a contributing factor. The studies conducted have been limited by the challenges of separating culture and genetics and there is no real evidence confirming or denying the possible role of genetic differences between ethnicities influencing the risk of developing eating disorders. However, if genetic differences are found to be an important risk factor for the development of eating disorders, the evidence would fit in well with the AFFH. People of European and African have some distinct genetic differences. It is possible that the genes promoting AN characteristics were more advantageous in European ancestors compared to African ancestors because of the vastly different climates and consequent patterns of food availability. The migration patterns of Africans versus all other ethnic groups, including Europeans, may have selected for different genes as well. Europeans migrated significantly further than Africans which may have made genes allowing people to continue to migrate despite food scarcity a much more significant advantage. This may explain why AN is much more prevalent in people of European descent compared to other ethnicities. Culture has an important role in modern day AN. To receive the diagnosis of AN, an individual must have a preoccupation with their weight which is likely a cultural construct stemming from the beauty ideal of a thin shape. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Keel and Klump (2003)", "previouslyFormattedCitation" : "(Keel and Klump 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Keel and Klump (2003) found that if preoccupation with body weight is removed as a diagnostic criterion, a similar proportion of the general and psychiatric populations in Western and non-Western countries are found to have the disease. Using the AFFH which suggests that food restriction causes the metabolic changes leading to the symptoms of AN, regardless of if the goal is to lose weight or not, other food restriction behaviours like fasting, or decreased food consumption because of stress could also bring on the disease. However, in these cases, the disease would not be considered AN because the individuals would not have a weight preoccupation. Further support for the AFFH and rogue hibernation theories comes from the general lack of association of AN with genes related to serotonin, dopamine, and opioids which all play roles in the pleasure and enjoyment of food. Though levels of serotonin, dopamine, opioids, and related metabolites and receptors appear to be altered in people in AN, the lack of evidence showing a link between relevant genes and the disease indicate that the abnormal physiological state may be a result of the disease, rather than the cause of it. 5.4 Thrifty gene hypothesis Fewer theories exist about how symptoms of BN and BED previously could have been an evolutionary advantage compared to AN. The leading theory relates to the thrifty genotype hypothesis which focuses on how historically, having extra fat stores were protective. Adipocytes are used for fat storage in the form of triglycerides. Having these fat stores play a role in helping to avoid malnutrition, regulate reproduction, and allow for survival during variations in the energy supply. Both hunter/gathers as well as agricultural societies experienced fluctuations in the food supply. However hunter/gathers were able to migrate more easily decreasing the fluctuation in energy available to them which relates back to the AFFH for AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S1464793105006974", "ISSN" : "1464-7931", "PMID" : "16677431", "abstract" : "Human susceptibility to obesity is an unusual phenomenon amongst animals. An evolutionary analysis, identifying factors favouring the capacity for fat deposition, may aid in the development of preventive public health strategies. This article considers the proximate causes, ontogeny, fitness value and evolutionary history of human fat deposition. Proximate causes include diet composition, physical activity level, feeding behaviour, endocrine and genetic factors, psychological traits, and exposure to broader environmental factors. Fat deposition peaks during late gestation and early infancy, and again during adolescence in females. As in other species, human fat stores not only buffer malnutrition, but also regulate reproduction and immune function, and are subject to sexual selection. Nevertheless, our characteristic ontogenetic pattern of fat deposition, along with relatively high fatness in adulthood, contrasts with the phenotype of other mammals occupying the tropical savannah environment in which hominids evolved. The increased value of energy stores in our species can be attributed to factors increasing either uncertainty in energy availability, or vulnerability to that uncertainty. Early hominid evolution was characterised by adaptation to a more seasonal environment, when selection would have favoured general thriftiness. The evolution of the large expensive brain in the genus Homo then favoured increased energy stores in the reproducing female, and in the offspring in early life. More recently, the introduction of agriculture has had three significant effects: exposure to regular famine; adaptation to a variety of local niches favouring population-specific adaptations; and the development of social hierarchies which predispose to differential exposure to environmental pressures. Thus, humans have persistently encountered greater energy stress than that experienced by their closest living relatives during recent evolution. The capacity to accumulate fat has therefore been a major adaptive feature of our species, but is now increasingly maladaptive in the modern environment where fluctuations in energy supply have been minimised, and productivity is dependent on mechanisation rather than physical effort. Alterations to the obesogenic environment are predicted to play a key role in reducing the prevalence of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Wells", "given" : "Jonathan C K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "183-205", "title" : "The evolution of human fatness and susceptibility to obesity: an ethological approach", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wells 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wells 2006). Mass immigration is also thought to have selected for thrifty genes because people are often escaping food scarce conditions and may be exposed to more food scarcity through the immigration process and intense competition for food ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1017/S1464793105006974", "ISSN" : "1464-7931", "PMID" : "16677431", "abstract" : "Human susceptibility to obesity is an unusual phenomenon amongst animals. An evolutionary analysis, identifying factors favouring the capacity for fat deposition, may aid in the development of preventive public health strategies. This article considers the proximate causes, ontogeny, fitness value and evolutionary history of human fat deposition. Proximate causes include diet composition, physical activity level, feeding behaviour, endocrine and genetic factors, psychological traits, and exposure to broader environmental factors. Fat deposition peaks during late gestation and early infancy, and again during adolescence in females. As in other species, human fat stores not only buffer malnutrition, but also regulate reproduction and immune function, and are subject to sexual selection. Nevertheless, our characteristic ontogenetic pattern of fat deposition, along with relatively high fatness in adulthood, contrasts with the phenotype of other mammals occupying the tropical savannah environment in which hominids evolved. The increased value of energy stores in our species can be attributed to factors increasing either uncertainty in energy availability, or vulnerability to that uncertainty. Early hominid evolution was characterised by adaptation to a more seasonal environment, when selection would have favoured general thriftiness. The evolution of the large expensive brain in the genus Homo then favoured increased energy stores in the reproducing female, and in the offspring in early life. More recently, the introduction of agriculture has had three significant effects: exposure to regular famine; adaptation to a variety of local niches favouring population-specific adaptations; and the development of social hierarchies which predispose to differential exposure to environmental pressures. Thus, humans have persistently encountered greater energy stress than that experienced by their closest living relatives during recent evolution. The capacity to accumulate fat has therefore been a major adaptive feature of our species, but is now increasingly maladaptive in the modern environment where fluctuations in energy supply have been minimised, and productivity is dependent on mechanisation rather than physical effort. Alterations to the obesogenic environment are predicted to play a key role in reducing the prevalence of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Wells", "given" : "Jonathan C K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Reviews", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "183-205", "title" : "The evolution of human fatness and susceptibility to obesity: an ethological approach", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wells 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wells 2006). As agricultural societies developed, people were less able to relocate to avoid famine and as a result, “thrifty” genes were selected for ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "V", "family" : "Neel", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nutrition Reviews", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "S2-S7", "title" : "The thrifty genotype in 1998", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "V", "family" : "Neel", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Human Genetics", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "1962" ] ] }, "page" : "353-362", "title" : "Diabetes mellitus: a \"thrifty\" genotype rendered detrimental by \"progress\"", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1017/S1464793105006974", "ISSN" : "1464-7931", "PMID" : "16677431", "abstract" : "Human susceptibility to obesity is an unusual phenomenon amongst animals. An evolutionary analysis, identifying factors favouring the capacity for fat deposition, may aid in the development of preventive public health strategies. This article considers the proximate causes, ontogeny, fitness value and evolutionary history of human fat deposition. Proximate causes include diet composition, physical activity level, feeding behaviour, endocrine and genetic factors, psychological traits, and exposure to broader environmental factors. Fat deposition peaks during late gestation and early infancy, and again during adolescence in females. As in other species, human fat stores not only buffer malnutrition, but also regulate reproduction and immune function, and are subject to sexual selection. Nevertheless, our characteristic ontogenetic pattern of fat deposition, along with relatively high fatness in adulthood, contrasts with the phenotype of other mammals occupying the tropical savannah environment in which hominids evolved. The increased value of energy stores in our species can be attributed to factors increasing either uncertainty in energy availability, or vulnerability to that uncertainty. Early hominid evolution was characterised by adaptation to a more seasonal environment, when selection would have favoured general thriftiness. The evolution of the large expensive brain in the genus Homo then favoured increased energy stores in the reproducing female, and in the offspring in early life. More recently, the introduction of agriculture has had three significant effects: exposure to regular famine; adaptation to a variety of local niches favouring population-specific adaptations; and the development of social hierarchies which predispose to differential exposure to environmental pressures. Thus, humans have persistently encountered greater energy stress than that experienced by their closest living relatives during recent evolution. The capacity to accumulate fat has therefore been a major adaptive feature of our species, but is now increasingly maladaptive in the modern environment where fluctuations in energy supply have been minimised, and productivity is dependent on mechanisation rather than physical effort. Alterations to the obesogenic environment are predicted to play a key role in reducing the prevalence of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Wells", "given" : "Jonathan C K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Reviews", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "183-205", "title" : "The evolution of human fatness and susceptibility to obesity: an ethological approach", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Neel 1962, 1999; Wells 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Neel 1962, 1999; Wells 2006). These genes which previously promoted survival in food insecure environments are no longer protective in the modern “obesogenic” environment, characterized by food that is inexpensive, abundant, served in large portions, and heavily marketed while demands for physical activity decrease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.psc.2011.08.005", "ISSN" : "1558-3147", "PMID" : "22098799", "abstract" : "The obesity epidemic in the United States has proven difficult to reverse. We have not been successful in helping people sustain the eating and physical activity patterns that are needed to maintain a healthy body weight. There is growing recognition that we will not be able to sustain healthy lifestyles until we are able to address the environment and culture that currently support unhealthy lifestyles. Addressing obesity requires an understanding of energy balance. From an energy balance approach it should be easier to prevent obesity than to reverse it. Further, from an energy balance point of view, it may not be possible to solve the problem by focusing on food alone. Currently, energy requirements of much of the population may be below the level of energy intake than can reasonably be maintained over time. Many initiatives are underway to revise how we build our communities, the ways we produce and market our foods, and the ways we inadvertently promote sedentary behavior. Efforts are underway to prevent obesity in schools, worksites, and communities. It is probably too early to evaluate these efforts, but there have been no large-scale successes in preventing obesity to date. There is reason to be optimistic about dealing with obesity. We have successfully addressed many previous threats to public health. It was probably inconceivable in the 1950s to think that major public health initiatives could have such a dramatic effect on reducing the prevalence of smoking in the United States. Yet, this serious problem was addressed via a combination of strategies involving public health, economics, political advocacy, behavioral change, and environmental change. Similarly, Americans have been persuaded to use seat belts and recycle, addressing two other challenges to public health. But, there is also reason to be pessimistic. Certainly, we can learn from our previous efforts for social change, but we must realize that our challenge with obesity may be greater. In the other examples cited, we had clear goals in mind. Our goals were to stop smoking, increase the use of seatbelts, and increase recycling. The difficulty of achieving these goals should not be minimized, but they were clear and simple goals. In the case of obesity, there is no clear agreement about goals. Moreover, experts do not agree on which strategies should be implemented on a widespread basis to achieve the behavioral changes in the population needed to reverse the high prevalence rates o\u2026", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Nia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Catenacci", "given" : "Victoria a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wyatt", "given" : "Holly R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "James O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Psychiatric Clinics of North America", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "717-732", "publisher" : "Elsevier Inc.", "title" : "Obesity: overview of an epidemic", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1017/S1464793105006974", "ISSN" : "1464-7931", "PMID" : "16677431", "abstract" : "Human susceptibility to obesity is an unusual phenomenon amongst animals. An evolutionary analysis, identifying factors favouring the capacity for fat deposition, may aid in the development of preventive public health strategies. This article considers the proximate causes, ontogeny, fitness value and evolutionary history of human fat deposition. Proximate causes include diet composition, physical activity level, feeding behaviour, endocrine and genetic factors, psychological traits, and exposure to broader environmental factors. Fat deposition peaks during late gestation and early infancy, and again during adolescence in females. As in other species, human fat stores not only buffer malnutrition, but also regulate reproduction and immune function, and are subject to sexual selection. Nevertheless, our characteristic ontogenetic pattern of fat deposition, along with relatively high fatness in adulthood, contrasts with the phenotype of other mammals occupying the tropical savannah environment in which hominids evolved. The increased value of energy stores in our species can be attributed to factors increasing either uncertainty in energy availability, or vulnerability to that uncertainty. Early hominid evolution was characterised by adaptation to a more seasonal environment, when selection would have favoured general thriftiness. The evolution of the large expensive brain in the genus Homo then favoured increased energy stores in the reproducing female, and in the offspring in early life. More recently, the introduction of agriculture has had three significant effects: exposure to regular famine; adaptation to a variety of local niches favouring population-specific adaptations; and the development of social hierarchies which predispose to differential exposure to environmental pressures. Thus, humans have persistently encountered greater energy stress than that experienced by their closest living relatives during recent evolution. The capacity to accumulate fat has therefore been a major adaptive feature of our species, but is now increasingly maladaptive in the modern environment where fluctuations in energy supply have been minimised, and productivity is dependent on mechanisation rather than physical effort. Alterations to the obesogenic environment are predicted to play a key role in reducing the prevalence of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Wells", "given" : "Jonathan C K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Reviews", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "183-205", "title" : "The evolution of human fatness and susceptibility to obesity: an ethological approach", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/S0140-6736(11)60813-1", "ISSN" : "1474-547X", "PMID" : "21872749", "abstract" : "The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers.", "author" : [ { "dropping-particle" : "", "family" : "Swinburn", "given" : "Boyd a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sacks", "given" : "Gary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Kevin D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Klim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finegood", "given" : "Diane T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moodie", "given" : "Marjory L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gortmaker", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-3", "issue" : "9793", "issued" : { "date-parts" : [ [ "2011", "8", "27" ] ] }, "page" : "804-814", "publisher" : "Elsevier Ltd", "title" : "The global obesity pandemic: shaped by global drivers and local environments", "type" : "article-journal", "volume" : "378" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wells 2006; Mitchell et al. 2011; Swinburn et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wells 2006; Mitchell et al. 2011; Swinburn et al. 2011).While the thrifty gene hypothesis provides an explanation for the underlying predisposition to obesity, it alone does not explain many of the disordered eating patterns observed. In particular, it does not explain AN, which has an underlying advantage of allowing people to function well despite having little energy available to them. However, the development of BN involving a cycle of binging and purging, BED which is similar to BN but without purging after periods of binging, as well as people with AN who also binge ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/0954026031000136839", "ISSN" : "0954-0261", "PMID" : "15276960", "abstract" : "Eating disorders rank among the most debilitating psychiatric disturbances that affect young women. Knowledge has increased in recent years about the two major eating disorders, anorexia nervosa (AN) and bulimia nervosa (BN); however, much remains unknown. This review article will provide an overview of the epidemiology, proposed risk factors and clinical features of AN, and BN, as well as current recommendations for evaluation and treatment of these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Klein", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Review of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003", "8" ] ] }, "page" : "205-216", "title" : "Eating disorders", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Klein and Walsh 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Klein and Walsh 2003) may in part be explained by the thrifty genotype hypothesis. Both BN and BED involve binging on food, estimated to be between 3000 – 4500kcal in a binge episode ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.20728", "ISSN" : "1098-108X", "PMID" : "19610126", "abstract" : "OBJECTIVE: Binge eating, a cardinal symptom of bulimia nervosa (BN) and binge eating disorder (BED), continues to pose challenges in terms of its definition and thus construct validity and clinical utility. This article reviews the available empirical data that support or refute the current DSM-IV-TR defined characteristics of a binge episode. METHOD: A systematic literature review was conducted using Medline/PubMed electronic database on DSM-IV-TR defined binge characteristics and associated attributes. RESULTS: Data support the current DSM guidelines indicating that binge episodes typically occur in less than 2 h. Size of binge episodes has variability across BN and BED diagnostic groups. Loss of control (LOC) continues to be a core feature of binge eating. Negative affect is the most widely reported antecedent. Strikingly, little is known about binge episodes among individuals with anorexia nervosa-binge/purge subtype. DISCUSSION: Available empirical evidence supports the current DSM duration and LOC attributes of a binge episode in BN and BED. However, a more controversial issues is the extent to which size is important in the definition of a binge episode (e.g., subjective vs. objective episodes) across diagnostic categories and the extent to which binge size informs prognosis, treatment, and clinical outcomes. Further study of binge eating attributes in AN is needed.", "author" : [ { "dropping-particle" : "", "family" : "Wolfe", "given" : "Barbara E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baker", "given" : "Christina Wood", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smith", "given" : "Adrian T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kelly-Weeder", "given" : "Susan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2009", "12" ] ] }, "page" : "674-686", "title" : "Validity and utility of the current definition of binge eating", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Wolfe et al. 2009)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Wolfe et al. 2009). It is plausible that the loss of control and drive to eat, particularly energy dense foods, is caused by the same genes that previously promoted fat accumulation and food consumption according to the thrifty gene hypothesis. The historical food context may also help explain the benefits of binge eating. In hunter gather societies, a successful hunt would provide a large quantity of food that would be shared. Being able to consume large amounts of food in a short time span would be beneficial to individuals, allowing them to have a greater portion of the available food. Furthermore, before the invention of refrigeration and preservation techniques, food had a relatively short life span and being able to consume large quantities before the food became unsafe to eat would have been advantageous. The purging behaviour seen in some people with AN and those with BN may be a modern iteration of the historical benefits of purging. Prior to the development of the obesogenic environment, it is unlikely that many people were able to find enough food to binge on to gain an undesirable amount of weight and thinness may not have been idealized as it now is in Western society. However, with the current overabundance of food available it is very easy for people to gain weight and most people with BN are within normal weight ranges ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev.med.51.1.299", "ISSN" : "0066-4219", "PMID" : "10774466", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frank", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2000", "1" ] ] }, "page" : "299-313", "title" : "Anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2000)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2000) while those with BED are overweight or obese ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1542/peds.2011-3663", "ISSN" : "1098-4275", "PMID" : "22802602", "abstract" : "OBJECTIVE: Anorexia nervosa and bulimia nervosa (BN) are rare, but eating disorders not otherwise specified (EDNOS) are relatively common among female participants. Our objective was to evaluate whether BN and subtypes of EDNOS are predictive of developing adverse outcomes. METHODS: This study comprised a prospective analysis of 8594 female participants from the ongoing Growing Up Today Study. Questionnaires were sent annually from 1996 through 2001, then biennially through 2007 and 2008. Participants who were 9 to 15 years of age in 1996 and completed at least 2 consecutive questionnaires between 1996 and 2008 were included in the analyses. Participants were classified as having BN (\u2265 weekly binge eating and purging), binge eating disorder (BED; \u2265 weekly binge eating, infrequent purging), purging disorder (PD; \u2265 weekly purging, infrequent binge eating), other EDNOS (binge eating and/or purging monthly), or nondisordered. RESULTS: BN affected \u223c1% of adolescent girls; 2% to 3% had PD and another 2% to 3% had BED. Girls with BED were almost twice as likely as their nondisordered peers to become overweight or obese (odds ratio [OR]: 1.9 [95% confidence interval: 1.0-3.5]) or develop high depressive symptoms (OR: 2.3 [95% confidence interval: 1.0-5.0]). Female participants with PD had a significantly increased risk of starting to use drugs (OR: 1.7) and starting to binge drink frequently (OR: 1.8). CONCLUSIONS: PD and BED are common and predict a range of adverse outcomes. Primary care clinicians should be made aware of these disorders, which may be underrepresented in eating disorder clinic samples. Efforts to prevent eating disorders should focus on cases of subthreshold severity.", "author" : [ { "dropping-particle" : "", "family" : "Field", "given" : "Alison E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sonneville", "given" : "Kendrin R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Micali", "given" : "Nadia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crosby", "given" : "Ross D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swanson", "given" : "Sonja a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Laird", "given" : "Nan M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solmi", "given" : "Francesca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Horton", "given" : "Nicholas J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Pediatrics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "e289-295", "title" : "Prospective association of common eating disorders and adverse outcomes", "type" : "article-journal", "volume" : "130" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1038/oby.2004.181", "ISSN" : "1071-7323", "PMID" : "15483209", "abstract" : "OBJECTIVE: To explore the extent to which binge eating in the absence of compensatory behaviors (BE) is associated with psychiatric and medical symptoms in men and women and to control for the independent effects of BMI. RESEARCH METHODS AND PROCEDURES: A series of regression models was applied to questionnaire data on 8045 twins, 18 to 31 years old, from a population-based Norwegian registry. RESULTS: BE was significantly associated with elevated obesity, overweight, symptoms of eating disorders, symptoms of anxiety and depression, panic attacks, depressive episodes, and reduced life satisfaction in both men and women. In women, BE was independently associated with insomnia and early menarche. In men, BE was independently associated with specific phobia, daily smoking, alcohol use, use of pain medication, impairment due to mental health, neck-shoulder, lower back, and chronic muscular pain, and impairment due to physical health. Both men and women with BE reported higher rates of psychiatric treatment. DISCUSSION: Our results indicate that there is substantial comorbidity between BE and psychiatric symptoms independently of BMI for both men and women. Medical symptoms co-occur less frequently than previously reported from treatment-seeking populations in women. Across all domains, the array of symptoms exhibited by men with BE was broader than that observed in women with BE. This observation suggests the importance of considering gender differences in future studies of psychiatric and medical morbidity, binge eating, and obesity.", "author" : [ { "dropping-particle" : "", "family" : "Reichborn-Kjennerud", "given" : "Ted", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sullivan", "given" : "Patrick F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tambs", "given" : "Kristian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harris", "given" : "Jennifer R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Obesity research", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2004", "9" ] ] }, "page" : "1445-1454", "title" : "Psychiatric and medical symptoms in binge eating in the absence of compensatory behaviors", "type" : "article-journal", "volume" : "12" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Reichborn-Kjennerud et al. 2004; Field et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Reichborn-Kjennerud et al. 2004; Field et al. 2012). It is possible that people with BN, who by definition of the disease are preoccupied and concerned about their weight ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "American Psychiatric Association", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "American Psychiatric Association", "publisher-place" : "Arlington, Virginia", "title" : "Diagnostic and statistical manual of mental disorders", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(American Psychiatric Association 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(American Psychiatric Association 2013) are driven by the genes that would be associated with the thrifty gene hypothesis to eat, however because of societal pressures to be thin have adopted purging behaviours to compensate. Though the inter-female competition theory is specific to AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Abed", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of Medical Psychology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1998" ] ] }, "page" : "525-547", "title" : "The sexual competition hypothesis for eating disorders", "type" : "article-journal", "volume" : "71" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Abed 1998)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Abed 1998), it is possible that the same motivation to attract a high quality partner that is proposed to cause AN may also cause purging behaviour in BN. Support of the role of the thrifty gene hypothesis in conjunction with inter female competition in the development of BN and BED can be found by comparing and contrasting the diseases. Applying the thrifty gene concept, we hypothesize that the root causes of binging are the same in BN and BED. There is a biological drive to consume food when available which is a relic from the period of time in human evolution when food was scarce. The significant difference between BN and BED is that BN involves purging in addition to binging which may be a cultural linked behaviour or a combination of AN and BED present in an individual. Evidence supporting this theory comes from the risk factors for the two diseases. The risk of developing BN increases in family environments in which parents have high expectations and focus on weight as well as when individuals are involved with activities which promote a lean shape ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/0954026031000136839", "ISSN" : "0954-0261", "PMID" : "15276960", "abstract" : "Eating disorders rank among the most debilitating psychiatric disturbances that affect young women. Knowledge has increased in recent years about the two major eating disorders, anorexia nervosa (AN) and bulimia nervosa (BN); however, much remains unknown. This review article will provide an overview of the epidemiology, proposed risk factors and clinical features of AN, and BN, as well as current recommendations for evaluation and treatment of these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Klein", "given" : "D A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Review of Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2003", "8" ] ] }, "page" : "205-216", "title" : "Eating disorders", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Klein and Walsh 2003)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Klein and Walsh 2003). This suggests that people with BN have been taught that being overweight is bad and use purging to avoid it. The ratio of males to females with BN is lower than that of BED. While both males and females are influenced by media exposure for beauty ideals, there is evidence that it affects females more, particularly the ideal of being thin ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cpr.2012.10.011", "ISSN" : "1873-7811", "PMID" : "23232051", "abstract" : "BACKGROUND: Older meta-analyses of the effects of the media's portrayal of the ideal physique have found small effects revealing that exposure to the ideal physique increases body image concerns. These meta-analyses also included correlational, quasi-experimental, and experimental studies, with limited examination of moderators and other relevant outcomes besides body image. METHODS: We conducted a systematic literature search and identified 33 experimental (i.e., pre and post data for both experimental and control groups) laboratory studies examining the effects of acute exposure to the media's portrayal of the ideal physique on eating disorder symptoms (i.e., body image, positive affect, negative affect, self-esteem, anger, anxiety and depression) and the mechanisms that moderate this effect. RESULTS: Fourteen separate meta-analyses revealed a range of small to moderate effect sizes for change in outcomes from pre to post for both experimental and control groups. Exposure to images of the ideal physique resulted in small effect sizes for increased depression and anger and decreased self-esteem and positive affect. Moderator analyses revealed moderate effect sizes for increased depression and body dissatisfaction among high-risk participants. CONCLUSIONS: This meta-analysis makes it clear that media exposure of the ideal physique results in small changes in eating disorder symptoms, particularly with participants at high risk for developing an eating disorder. Further research is needed to examine the longitudinal effects of media exposure of eating disorder symptoms.", "author" : [ { "dropping-particle" : "", "family" : "Hausenblas", "given" : "Heather a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Campbell", "given" : "Anna", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Menzel", "given" : "Jessie E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Doughty", "given" : "Jessica", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Levine", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson", "given" : "J Kevin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Psychology Review", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2013", "2" ] ] }, "page" : "168-181", "publisher" : "Elsevier Ltd", "title" : "Media effects of experimental presentation of the ideal physique on eating disorder symptoms: a meta-analysis of laboratory studies", "type" : "article-journal", "volume" : "33" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hausenblas et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hausenblas et al. 2013). Therefore, it is logical that if BN and BED both stem from the same genetic predisposition to over consume food, more females would have BN rather than BED because of a greater impact of societal standards of beauty. The peak incidence of developing the disease provide further evidence. For BN the peak incidence is between 17.0 and 19.7 years of age ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fornari", "given" : "Victor M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Braun", "given" : "Devra L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sunday", "given" : "Suzanne R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sandberg", "given" : "David E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matthews", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Ii-lun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mandel", "given" : "Francine S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Halmi", "given" : "Katherine A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katz", "given" : "Jack L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shore", "given" : "North", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hospitalcornell", "given" : "Universiy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Compr Psychiatry", "id" : "ITEM-3", "issue" : "6", "issued" : { "date-parts" : [ [ "1994" ] ] }, "page" : "450-456", "title" : "Seasonal patterns in eating disorder subgroups", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Fornari et al. 1994; Favaro et al. 2003; Hudson et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Fornari et al. 1994; Favaro et al. 2003; Hudson et al. 2008) whereas BED appears to be more equally distributed across the lifespan ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0276-3478", "PMID" : "10191993", "abstract" : "OBJECTIVE: The authors investigated the prevalence of binge eating behavior in a general female Austrian population. METHOD: A random sample of 1,000 women (age range 15a to 85a) was interviewed by dieticians over the phone. Some screening instruments were used to detect binge eating behavior. RESULTS: Of the entire sample, 122 met the diagnostic criteria for binge eating, 84 for binge eating syndrome, and 33 for binge eating disorder (BED). The point prevalence of bulimia nervosa was 1.5%. Women with binge eating episodes carried out more frequently one or more diets within the previous year, and more frequently exhibited a restrained eating behavior than did women without binge eating behavior. Underweight women more often met the diagnostic criteria for bulimia nervosa nonpurging type than did normal weight, overweight, and obese women, while overweight and obese women more frequently met the diagnostic criteria for BED. DISCUSSION: Our findings indicate that binge eating appears to be a fairly common behavior in women. Dieting, chronic restrained eating, and excessive exercise may be important triggers for BED and bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Kinzl", "given" : "J F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Traweger", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Trefalt", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mangweth", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biebl", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "1999", "4" ] ] }, "page" : "287-292", "title" : "Binge eating disorder in females: a population-based investigation", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Grucza", "given" : "Richard A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Przybeck", "given" : "T R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cloninger", "given" : "C R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Comprehensive Psychiatry", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "124-131", "title" : "Prevalence and correlates of binge eating disorder in a community sample", "type" : "article-journal", "volume" : "48" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woo", "given" : "Meghan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Zhun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torres", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Xiao-li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striegel-moore", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "S15-S21", "title" : "Prevalence and correlates of eating disorders in Latinos in the United States", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kinzl et al. 1999; Alegria et al. 2007; Grucza et al. 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kinzl et al. 1999; Alegria et al. 2007; Grucza et al. 2007). Biologically, the need to store energy to survive future famines would continue to occur across the lifespan, however concerns about being at an ideal weight to attract an appropriate partner would be more relevant at the younger ages seen in BN patients. We found that compared to BN, BED is more equally distributed across ethnicities ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/eat.parative", "author" : [ { "dropping-particle" : "", "family" : "Marques", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chih-nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chosak", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belo Diniz", "given" : "Juliana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "412-420", "title" : "Comparative prevalence, correlates of impairment, and service utilization for eating disorders across U.S. ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woo", "given" : "Meghan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cao", "given" : "Zhun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Torres", "given" : "Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meng", "given" : "Xiao-li", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striegel-moore", "given" : "Ruth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "S15-S21", "title" : "Prevalence and correlates of eating disorders in Latinos in the United States", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "0883-6612", "PMID" : "9989331", "abstract" : "This article examined the prevalence of binge eating disorder (BED), obesity, and depressive symptomatology in a biracial, population-based cohort of men and women participating in a longitudinal study of cardiovascular risk factor development. The Revised Questionnaire on Eating and Weight Patterns was used to establish BED status among the 3,948 (55% women, 48% Black) participants (age 28-40 years). Body mass index (BMI: kg/m2) was used to define overweight (BMI > or = 27.3 in women and > or = 27.8 in men). Depressive symptomatology was assessed with the Center for Epidemiologic Study Depression Scale. Prevalence of BED was 1.5% in the cohort overall, with similar rates among Black women, White women, and White men. Black men had substantially lower BED rates. Depressive symptomatology was markedly higher among individuals with BED. Among overweight participants, BED prevalence (2.9%) was almost double that of the overall cohort. There were no differences in BED rates between over-weight Black and White women. Thus, BED was common in the general population, with comparable rates among Black women, White women, and White men, but low rates among Black men. Obesity was associated with substantially higher prevalence of BED. Treatment studies that target obese men and minority women with BED are indicated.", "author" : [ { "dropping-particle" : "", "family" : "Smith", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marcus", "given" : "M D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lewis", "given" : "C E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fitzgibbon", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiner", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Behavioral Medicine", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "1998", "1" ] ] }, "page" : "227-232", "title" : "Prevalence of binge eating disorder, obesity, and depression in a biracial cohort of young adults", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/eat", "author" : [ { "dropping-particle" : "", "family" : "Nicdao", "given" : "Ethel G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hong", "given" : "Seunghye", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takeuchi", "given" : "David T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "S22-S26", "title" : "Prevalence and correlates of eating disorders among Asian Americans: Results from the National Latino and Asian American Study", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "ISSN" : "0002-953X", "PMID" : "12832249", "abstract" : "OBJECTIVE: Epidemiological studies of eating disorders in the United States have focused on white women and girls, and the prevalence of eating disorders in ethnic minority groups is unknown. This study examined the prevalence of anorexia nervosa, bulimia nervosa, and binge eating disorder in a geographically and economically diverse community sample of young white and black women who previously participated in the 10-year National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study. METHOD: All NHLBI Growth and Health Study participants were recruited for this study. A two-stage case finding method was used, consisting of a telephone screening (sensitivity=0.90, specificity=0.98) and an in-person confirmatory diagnostic interview. RESULTS: A total of 86.0% of the original NHLBI Growth and Health Study cohort participated, including 985 white women (mean age=21.3) and 1,061 black women (mean age=21.5). Fifteen white (1.5%) and no black women met lifetime criteria for anorexia nervosa; more white women (N=23, 2.3%) than black women (N=4, 0.4%) met criteria for bulimia nervosa; binge eating disorder also was more common among white women (N=27, 2.7%) than black women (N=15, 1.4%). Few women (white: N=16, 28.1%; black: N=1, 5.3%) ever had received treatment for an eating disorder. CONCLUSIONS: Results suggest that eating disorders, especially anorexia nervosa and bulimia nervosa, are more common among white women than among black women. The low treatment rates in both groups suggest that health professionals need to be more alert to the possibility of eating disorders in women.", "author" : [ { "dropping-particle" : "", "family" : "Striegel-Moore", "given" : "Ruth H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohm", "given" : "Faith a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraemer", "given" : "Helena C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "C Barr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Patricia B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiber", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-5", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "page" : "1326-1331", "title" : "Eating disorders in white and black women", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1353/hpu.2013.0027.Classification", "author" : [ { "dropping-particle" : "", "family" : "Taylor", "given" : "J Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caldwell", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baser", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matuski", "given" : "Niki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faison", "given" : "Nakesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Health Care Poor Underserved", "id" : "ITEM-6", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "289-310", "title" : "Classification and correlates of eating disorders among blacks: Findings from the National Survey of American Life", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Smith et al. 1998; Striegel-Moore et al. 2003; Alegria et al. 2007; Nicdao et al. 2007; Marques et al. 2011; Taylor et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Smith et al. 1998; Striegel-Moore et al. 2003; Alegria et al. 2007; Nicdao et al. 2007; Marques et al. 2011; Taylor et al. 2013). This could in part be because weight preoccupation is predominantly a Western concern ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1351-0126", "PMID" : "11896858", "abstract" : "Anorexia nervosa is currently considered a disorder confined to Western culture. Its recent identification in non-Western societies and different subcultures within the Western world has provoked a theory that Western cultural ideals of slimness and beauty have infiltrated these societies. The biomedical definition of anorexia nervosa emphasizes fat-phobia in the presentation of anorexia nervosa. However, evidence exists that suggests anorexia nevosa can exist without the Western fear of fatness and that this culturally biased view of anorexia nervosa may obscure health care professionals' understanding of a patient's own cultural reasons for self-starvation, and even hinder their recovery.", "author" : [ { "dropping-particle" : "", "family" : "Simpson", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric and Mental Health Nursing", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2002", "2" ] ] }, "page" : "65-71", "title" : "Anorexia nervosa and culture", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0002-953X", "PMID" : "11532731", "abstract" : "OBJECTIVE: Binge eating disorder was introduced in DSM-IV as a psychiatric disorder needing further study. This community-based study describes the relationship between race and clinical functioning in black and white women with and without binge eating disorder. METHOD: A group of 150 women with binge eating disorder (52 black, 98 white) and a race-matched group of 150 healthy comparison subjects were recruited from the community. Eating and psychiatric symptoms were assessed through interviews and self-report. RESULTS: Black and white women with binge eating disorder differed significantly on numerous eating disorder features, including binge frequency, restraint, history of other eating disorders, treatment-seeking behavior, and concerns with eating, weight, and shape. Black and white healthy comparison subjects differed significantly in obesity rates. CONCLUSIONS: For both black and white women, binge eating disorder was associated with significant impairment in clinical functioning. Yet, racial differences in clinical presentation underscore the importance of considering race in psychopathology research.", "author" : [ { "dropping-particle" : "", "family" : "Pike", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohm", "given" : "F a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striegel-Moore", "given" : "R H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilfley", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-2", "issue" : "9", "issued" : { "date-parts" : [ [ "2001", "9" ] ] }, "page" : "1455-1460", "title" : "A comparison of black and white women with binge eating disorder", "type" : "article-journal", "volume" : "158" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Pike et al. 2001; Simpson 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Pike et al. 2001; Simpson 2002), therefore people from non-Western countries who binge may not feel the same drive to purge compared to their Western counterparts. The thrifty genotype has been focused upon in this thesis, however it is important to note that the thrifty genotype is a controversial theory to explain obesity. Speakman has been one of the most vocal opponents of the thrifty genotype hypothesis. His main arguments include that mortality during times of famine is not enough to lead to genetic selection nor are the people who often die during famine, the elderly and the young the ones that would strongly influence the gene pool and that historical patterns of famine are incompatible with a selective hypothesis ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2008.161", "ISSN" : "1476-5497", "PMID" : "18852699", "abstract" : "Almost 50 years ago Neel proposed a hypothesis to explain the prevalence of obesity and diabetes in modern society--the 'thrifty gene' hypothesis. The fundamental basis of the hypothesis was that, in our early evolutionary history, genes, that promoted efficient fat deposition would have been advantageous because they allowed their holders to survive at periods of famine. In modern society, such genes are disadvantageous because they promote fat deposition in preparation for a famine that never comes, and the result is widespread obesity and diabetes. In recent years I, and others, have questioned some of the fundamental assumptions of this hypothesis--particularly focusing on whether differential survival of lean against obese in famines provides sufficient selective pressure for the spread of so-called 'thrifty genes'. These arguments have been criticized because famines not only affect survival but also fecundity, and obese people would be expected to sustain fecundity longer in the face of food shortages. In this paper, I show that the reduced fecundity argument is flawed because famines are almost universally followed by periods of enhanced fecundity, which offsets the decline observed during the famine itself. The net effect of famines on fecundity is consequently insufficient to rescue the thrifty gene idea. Elsewhere, I have suggested an alternative scenario that subsections of the population have a genetic predisposition to obesity due to an absence of selection, combined with genetic drift. The scenario presented earlier was based on evidence from prehistory concerning the release of our ancestors from heavy predation pressure around 2 million years ago. I suggest here that this is one of a number of potential scenarios based on random genetic drift that may explain the specific aetiology of the obesity epidemic. Together, these alternatives, based on central notion that genetic drift rather than positive selection was a dominant factor, may be called the 'drifty gene' hypothesis.", "author" : [ { "dropping-particle" : "", "family" : "Speakman", "given" : "J R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2008", "11" ] ] }, "page" : "1611-1617", "title" : "Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the 'drifty gene' hypothesis", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Speakman 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Speakman 2008). Others have agreed with Speakman that the mortality rates in famine are not sufficient to explain the possible genetic selection, however argue the effect of famine on fertility selection can explain the genetic selection. Speakman’s argument that the historical patterns of famine are incompatible with the thrifty genotype hypothesis has been strongly refuted, including by Neel himself ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2008.147", "ISSN" : "1476-5497", "PMID" : "18852700", "abstract" : "This article challenges Speakman's hypothesis that the modern genetic predisposition to obesity has arisen through random genetic drift in the two million years following predation release. We present evidence in support of the hypothesis that a mixture of famines and seasonal food shortages in the post-agricultural era have exerted natural selection in favour of fat storage; an effect most likely mediated through fertility, rather than viability, selection. We conclude that, far from being time to call off the search, recently developed genetic and bioinformatic methods will soon provide a definitive resolution to this long-standing 'thrifty gene' controversy.", "author" : [ { "dropping-particle" : "", "family" : "Prentice", "given" : "A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hennig", "given" : "B J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulford", "given" : "A J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2008", "11" ] ] }, "page" : "1607-1610", "title" : "Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release?", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Prentice et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Prentice et al. 2008). The original thrifty genotype hypothesis states that the selective pressure for thrifty genes would have existed during the Paleolithic era in hunter gather societies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "V", "family" : "Neel", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Human Genetics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1962" ] ] }, "page" : "353-362", "title" : "Diabetes mellitus: a \"thrifty\" genotype rendered detrimental by \"progress\"", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Neel 1962)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Neel 1962). It is generally accepted that famines and seasonal food shortages are much more applicable to agricultural societies in comparison to hunter gathers societies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1038/ijo.2008.147", "ISSN" : "1476-5497", "PMID" : "18852700", "abstract" : "This article challenges Speakman's hypothesis that the modern genetic predisposition to obesity has arisen through random genetic drift in the two million years following predation release. We present evidence in support of the hypothesis that a mixture of famines and seasonal food shortages in the post-agricultural era have exerted natural selection in favour of fat storage; an effect most likely mediated through fertility, rather than viability, selection. We conclude that, far from being time to call off the search, recently developed genetic and bioinformatic methods will soon provide a definitive resolution to this long-standing 'thrifty gene' controversy.", "author" : [ { "dropping-particle" : "", "family" : "Prentice", "given" : "A M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hennig", "given" : "B J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fulford", "given" : "A J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Obesity", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2008", "11" ] ] }, "page" : "1607-1610", "title" : "Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release?", "type" : "article-journal", "volume" : "32" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Prentice et al. 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Prentice et al. 2008). As an alternative to the thrifty genotype hypothesis, Speakman proposed what is now referred to as the drifty gene hypothesis proposing that obesity was previously selected against by the risk of predators. The upper limit of human weight was limited by predators as people who were too large to run away or adequately protect themselves would not survive. Speakman proposes that with the development of social behaviour, weapons, and fire the risk of predators was significantly decreased and that the distribution of body fatness increased because there were no longer any selective pressures to not have a higher BMI. Because the selective pressures to maintain a minimum weight were still in place, such as immune function and decreased risk of starvation, random mutations and drifting gradually increased the distribution of BMI in the population ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cmet.2007.06.004", "ISSN" : "1550-4131", "PMID" : "17618852", "abstract" : "The \"thrifty gene hypothesis\" suggests we evolved genes for efficient food collection and fat deposition to survive periods of famine and that now that food is continuously available, these genes are disadvantageous because they make us obese in preparation for a famine that never comes. However, famines are relatively infrequent modern phenomena that involve insufficient mortality for thrifty genes to propagate. I suggest here that early hominids would have been subjected to stabilizing selection for body fatness, with obesity selected against by the risk of predation. Around two million years ago predation was removed as a significant factor by the development of social behavior, weapons, and fire. The absence of predation led to a change in the population distribution of body fatness due to random mutations and drift. Because this novel hypothesis involves random drift, rather than directed selection, it explains why, even in Western society, most people are not obese.", "author" : [ { "dropping-particle" : "", "family" : "Speakman", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cell Metabolism", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2007", "7" ] ] }, "page" : "5-12", "title" : "A nonadaptive scenario explaining the genetic predisposition to obesity: the \"predation release\" hypothesis", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Speakman 2007)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Speakman 2007). Another evolutionary theory of obesity that has been proposed is the thrifty phenotype which proposes that maternal nutrition, low birth weight, and a prediction of low food sources cause an adaptive insulin resistance ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/ije/dyt133", "ISSN" : "1464-3685", "PMID" : "24159065", "author" : [ { "dropping-particle" : "", "family" : "Hales", "given" : "C N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barker", "given" : "D J P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Epidemiology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2013", "10" ] ] }, "page" : "1215-1222", "title" : "Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s11920-013-0408-x", "ISSN" : "1535-1645", "PMID" : "24057159", "abstract" : "The thrifty genotype and phenotype hypotheses were developed to explain the rapid increase in diabetes and obesity in developed countries around the world. Most subsequent \"thrifty\" research has focused on the early developmental origins of the metabolic syndrome and cardio-metabolic disease. The goal of this manuscript is to review an emerging line of research that uses a similar thrifty framework to understand the early developmental origins of eating-related phenotypes that have primary relevance to many psychiatric disorders. Given the important role of environmental adversity in various psychiatric disorders that involve overeating, and their early age of onset, it is likely that several thrifty mechanisms are relevant in this regard. Understanding the early origins of increased eating behaviour based on a thrifty model might point the way to highly targeted preventative interventions during critical periods of development, and provide a new way of addressing these common and difficult to treat disorders.", "author" : [ { "dropping-particle" : "", "family" : "Levitan", "given" : "Robert D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wendland", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Psychiatry Reports", "id" : "ITEM-2", "issue" : "11", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "page" : "408", "title" : "Novel \"thrifty\" models of increased eating behaviour", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hales and Barker 2013; Levitan and Wendland 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hales and Barker 2013; Levitan and Wendland 2013). The thrifty phenotype theory applies to diabetes reasonably well, however is limited for explaining obesity in developed countries. Very few mothers experience malnutrition during pregnancy despite the high prevalence of obesity in developed countries ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11920-013-0408-x", "ISSN" : "1535-1645", "PMID" : "24057159", "abstract" : "The thrifty genotype and phenotype hypotheses were developed to explain the rapid increase in diabetes and obesity in developed countries around the world. Most subsequent \"thrifty\" research has focused on the early developmental origins of the metabolic syndrome and cardio-metabolic disease. The goal of this manuscript is to review an emerging line of research that uses a similar thrifty framework to understand the early developmental origins of eating-related phenotypes that have primary relevance to many psychiatric disorders. Given the important role of environmental adversity in various psychiatric disorders that involve overeating, and their early age of onset, it is likely that several thrifty mechanisms are relevant in this regard. Understanding the early origins of increased eating behaviour based on a thrifty model might point the way to highly targeted preventative interventions during critical periods of development, and provide a new way of addressing these common and difficult to treat disorders.", "author" : [ { "dropping-particle" : "", "family" : "Levitan", "given" : "Robert D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wendland", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Psychiatry Reports", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2013", "11" ] ] }, "page" : "408", "title" : "Novel \"thrifty\" models of increased eating behaviour", "type" : "article-journal", "volume" : "15" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Levitan and Wendland 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Levitan and Wendland 2013). A final theory called the thrifty epigenotype combines the thrifty genotype and thrifty phenotype. It postulates that through genetic canalization, genes coding for a thrifty genotype have been well preserved in the genome across all ethnicities and in all individuals. The theory also suggests the epigenetics, changes in gene activity that are not caused by alternations of DNA sequences but DNA methylation, histone modifications, remodeling of chromatin, and non-coding RNAs, is a critical element which is in line with the thrifty genotype theory indicating that the fetal environment influences adult health ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/bies.20700", "ISSN" : "0265-9247", "PMID" : "18197594", "abstract" : "Obesity and type 2 diabetes arise from a set of complex gene-environment interactions. Explanations for the heritability of these syndromes and the environmental contribution to disease susceptibility are addressed by the \"thrifty genotype\" and the \"thrifty phenotype\" hypotheses. Here, the merits of both models are discussed and elements of them are used to synthesize a \"thrifty epigenotype\" hypothesis. I propose that: (1) metabolic thrift, the capacity for efficient acquisition, storage and use of energy, is an ancient, complex trait, (2) the environmentally responsive gene network encoding this trait is subject to genetic canalization and thereby has become robust against mutational perturbations, (3) DNA sequence polymorphisms play a minor role in the aetiology of obesity and type 2 diabetes-instead, disease susceptibility is predominantly determined by epigenetic variations, (4) corresponding epigenotypes have the potential to be inherited across generations, and (5) Leptin is a candidate gene for the acquisition of a thrifty epigenotype.", "author" : [ { "dropping-particle" : "", "family" : "St\u00f6ger", "given" : "Reinhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BioEssays", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2008", "2" ] ] }, "page" : "156-166", "title" : "The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes?", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(St\u00f6ger 2008)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(St?ger 2008). 5.5 Summary of evolutionary theoriesOf the evolutionary theories proposed, the AFFH best explains AN. Historically, having the motivation to be physically active, avoiding a preoccupation with food during caloric scarcity, and denying the seriousness of weight loss would enable individuals to migrate from food insecure to food secure areas and consequently increase their chances of survival and future reproduction. Though the people most commonly afflicted by AN are from Western countries where food scarcity is generally not an issue, ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.mehy.2013.12.003", "ISSN" : "1532-2777", "PMID" : "24373562", "abstract" : "Anorexia nervosa is a puzzling and often tragic disorder which causes the individual to self starve and hyper-exercise. We present a speculative analysis of the disorder which begins by acknowledging and accepting the adaptation to flee famine theory. This theory holds that anorexia nervosa results from activation of an archaic pathway that functioned well during human's nomadic past. We advance this idea by suggesting that the faulty signal indicating there is a famine, arises from misalignment of the circadian/circannual oscillations. Entry and exit from hibernation is dependent on these cycles, and we draw an analogy between hibernation and anorexia nervosa. We offer ideas for testing the hypothesis, and targeting these faulty signals.", "author" : [ { "dropping-particle" : "", "family" : "Scolnick", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mostofsky", "given" : "David I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Hypotheses", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2" ] ] }, "page" : "231-235", "publisher" : "Elsevier Ltd", "title" : "Anorexia nervosa: A rogue hibernation?", "type" : "article-journal", "volume" : "82" }, "uris" : [ "" ] } ], "mendeley" : { "manualFormatting" : "Scolnick and Mostofsky (2014)", "previouslyFormattedCitation" : "(Scolnick and Mostofsky 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }Scolnick and Mostofsky (2014) proposed that behaviour such as dieting could trigger the same physiological adaptations as living in a food scarce environment. The diagnosis of AN today requires an individual to be preoccupied with their weight. This may be best viewed as a contributing factor to the development of the disease, rather than a symptom of it. The AFFH is supported by the general patient characteristics of AN. AN mostly occurs in young females of child bearing age which would be the most desirable individuals to be able to flee from famine as more females than males required to re-establish the population. While the contribution of genetics and culture to ethnic differences in the prevalence of AN is still unresolved, if there are genetic differences the AFFH also can explain why AN is predominantly found in White populations ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-2909.129.5.747", "ISSN" : "0033-2909", "PMID" : "12956542", "abstract" : "The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity.", "author" : [ { "dropping-particle" : "", "family" : "Keel", "given" : "Pamela K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "Kelly L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Bulletin", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "2003", "9" ] ] }, "page" : "747-769", "title" : "Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology", "type" : "article-journal", "volume" : "129" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "0002-953X", "PMID" : "12832249", "abstract" : "OBJECTIVE: Epidemiological studies of eating disorders in the United States have focused on white women and girls, and the prevalence of eating disorders in ethnic minority groups is unknown. This study examined the prevalence of anorexia nervosa, bulimia nervosa, and binge eating disorder in a geographically and economically diverse community sample of young white and black women who previously participated in the 10-year National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study. METHOD: All NHLBI Growth and Health Study participants were recruited for this study. A two-stage case finding method was used, consisting of a telephone screening (sensitivity=0.90, specificity=0.98) and an in-person confirmatory diagnostic interview. RESULTS: A total of 86.0% of the original NHLBI Growth and Health Study cohort participated, including 985 white women (mean age=21.3) and 1,061 black women (mean age=21.5). Fifteen white (1.5%) and no black women met lifetime criteria for anorexia nervosa; more white women (N=23, 2.3%) than black women (N=4, 0.4%) met criteria for bulimia nervosa; binge eating disorder also was more common among white women (N=27, 2.7%) than black women (N=15, 1.4%). Few women (white: N=16, 28.1%; black: N=1, 5.3%) ever had received treatment for an eating disorder. CONCLUSIONS: Results suggest that eating disorders, especially anorexia nervosa and bulimia nervosa, are more common among white women than among black women. The low treatment rates in both groups suggest that health professionals need to be more alert to the possibility of eating disorders in women.", "author" : [ { "dropping-particle" : "", "family" : "Striegel-Moore", "given" : "Ruth H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohm", "given" : "Faith a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraemer", "given" : "Helena C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "C Barr", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daniels", "given" : "Stephen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Crawford", "given" : "Patricia B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schreiber", "given" : "George B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-2", "issue" : "7", "issued" : { "date-parts" : [ [ "2003", "7" ] ] }, "page" : "1326-1331", "title" : "Eating disorders in white and black women", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1353/hpu.2013.0027.Classification", "author" : [ { "dropping-particle" : "", "family" : "Taylor", "given" : "J Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Caldwell", "given" : "C H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baser", "given" : "R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Matuski", "given" : "Niki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Faison", "given" : "Nakesha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "J S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Health Care Poor Underserved", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "289-310", "title" : "Classification and correlates of eating disorders among blacks: Findings from the National Survey of American Life", "type" : "article-journal", "volume" : "24" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Keel and Klump 2003; Striegel-Moore et al. 2003; Taylor et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Keel and Klump 2003; Striegel-Moore et al. 2003; Taylor et al. 2013). The evolutionary pressure on Europeans in regards to food would be different compared to other regions of the world, therefore the genes promoting AN characteristics may have been more beneficial to Europeans compared to other ethnicities. The lack of association of genes related to serotonin, dopamine, and opioids which have been heavily explored because of their role in the pleasure and enjoyment of food indicate that altered levels of these neurotransmitters could be a result of the disease, rather than the cause of it, supporting the AFFH proposition that the biochemical changes are in response to famine. The thrifty gene hypothesis was initially developed to explain obesity. It may also explain the overeating behaviour seen in BN and BED. Historically, accumulating fat during times of food abundance would be beneficial to survival during periods of food insecurity as the fat could be used as energy stores. However, in the food abundant environments that people in the Western world live in today, the genes allowing for the overconsumption of food when it was available may be now encouraging chronic overconsumption. This can explain the binging seen in BN and BED, however to explain the purging seen in BN, an elaboration of the theory in necessary. The purging behaviour can be explained by the desire to stay thin despite the binging episodes. BN is predominantly found in Western cultures where thinness is idealized while BED is seen more equally across ethnicities. We propose that there could be common genes associated with BN and BED, with the desire to be thin determining which disease category individuals fall within based on purging behaviour. Examining the evolutionary theories of eating disorders can help future gene identification efforts by focusing on novel candidate genes as well as guiding the development of biological evidence to support the findings of GWAS. With the increasing use of GWAS approaches, evolutionary theories of eating disorders can also help determine new phenotypes to use as outcome variables. Genetic studies to date have provided limited success, which may be because they are focusing on symptoms of the disease, especially in AN, rather than the causes of it. For AN, abnormal neurotransmitter and hormone levels have been widely observed, but genetic association studies have been widely negative. However, if the altered neurotransmitter and hormone levels are a result of a physiological adaptation to low food consumption rather than one of the causes of the low food consumption as we propose, then we would not expect genes involved with the production and reception of those neurotransmitters and hormones to be altered. We propose that genes related to metabolism, specifically genes relating to mammalian hibernation in other species, would be more beneficial to investigate compared to genes involved in the production of neuropeptides. The genes relating to neuropeptide production in BN and BED may still be relevant, however because BED is equally prevalent worldwide, it indicates that the genes promoting an increased consumption of food may be more broadly found with almost undetectable effect sizes. Though looking at genes related to metabolism may lead to a further understand the genetic architecture of eating disorders, there is also the possibility that hormones relevant to eating disorders are yet to be discovered. Investigating metabolites, transcription factors, and protein profiles in people with eating disorders and comparing these to levels after recovery of the disease or between episodes as well as with controls may help to identify novel biomarkers and pathways in the etiology of eating disorders. 5.6 Coexistence of Anorexia Nervosa and Bulimia Nervosa in binge/purge subtype Anorexia Nervosa The evolutionary theories of eating disorders clearly distinguish between AN and the other two eating disorders, BN and BED. However, there is a significant amount of overlap between the diseases, particularly when looking at the subtypes of AN. AN(R) (Anorexia Nervosa restrictive subtype) is the diagnosis given to people who weigh less than 85% of what they should weight and consume a limited amount of calories per day while AN(BP) (Anorexia Nervosa binge/purge) is the diagnosis given to people who weigh less than 85% of their ideal weight and go through cycles of binging and purging ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "American Psychiatric Association", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "American Psychiatric Association", "publisher-place" : "Arlington, Virginia", "title" : "Diagnostic and statistical manual of mental disorders", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(American Psychiatric Association 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(American Psychiatric Association 2013). AN(BP) is very similar to BN, except that individuals with BN do not meet the weight cut offs for AN. In addition to the similarities of some of the diagnostic criteria, there is a significant amount of cross-over between those with AN(R), AN(BP), and BN. In seven years of follow-up, 49% of women initially diagnosed with AN crossed over between AN subtypes and 34% crossed over from AN to BN. Of those initially diagnosed with AN(R) 55% changed diagnostic categories to AN(BP) and 10% crossed over to a BN diagnosis. Women also crossed over from a diagnosis of BN to AN, with 14% crossing over to AN(BP) and 4% then crossing over to AN(R) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1176/appi.ajp.2007.07060951.Diagnostic", "author" : [ { "dropping-particle" : "", "family" : "Eddy", "given" : "Kamryn T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorer", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franko", "given" : "Debra L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tahilani", "given" : "Kavita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson-Brenner", "given" : "Heather", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzog", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "245-250", "title" : "Diagnostic crossover in Anorexia Nervosa and Bulimia Nerovsa: implications for the DSM-V", "type" : "article-journal", "volume" : "165" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Eddy et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Eddy et al. 2013). Below, we propose theories as to why the traits seen in BN, AN(R), and AN(BP) overlap from a genetic perspective. 5.6.1 Binge eating as protection against Anorexia Nervosa AN is considered the most dangerous of all mental disorders with more than 10% of patients dying from the disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Hoek 2006)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Hoek 2006). Theoretically, the denial of nutrients to the body seen in the restrictive subtype of AN could switch on a pathway encouraging the consumption of calories, explaining the binging behaviour seen in people with the binge/purge subtype of AN. The cross-over of patients from the subcategories of AN supports this theory when considering that more people cross over from the restrictive subtype to the binge/purge subtype ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1176/appi.ajp.2007.07060951.Diagnostic", "author" : [ { "dropping-particle" : "", "family" : "Eddy", "given" : "Kamryn T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorer", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franko", "given" : "Debra L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tahilani", "given" : "Kavita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson-Brenner", "given" : "Heather", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzog", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "245-250", "title" : "Diagnostic crossover in Anorexia Nervosa and Bulimia Nerovsa: implications for the DSM-V", "type" : "article-journal", "volume" : "165" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Eddy et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Eddy et al. 2013). Similarly, approximately 25 to 30% of people receiving treatment for BN have been found to previously have been diagnosed with AN while only 5% of people initially diagnosed with BN being diagnosed with either subtype of AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1146/annurev.med.51.1.299", "ISSN" : "0066-4219", "PMID" : "10774466", "abstract" : "Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.", "author" : [ { "dropping-particle" : "", "family" : "Kaye", "given" : "W H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klump", "given" : "K L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frank", "given" : "G K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Strober", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annual Review of Medicine", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2000", "1" ] ] }, "page" : "299-313", "title" : "Anorexia and bulimia nervosa", "type" : "article-journal", "volume" : "51" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Kaye et al. 2000)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Kaye et al. 2000). This supports that the restrictive behaviour seen in AN(R) may be difficult to maintain and consequently cross over to AN(BP) when the drive to eat becomes overwhelming. The cross-over of individuals from AN(BP) to BN shows that the binging behaviour may slowly lead to weight gain, as the only significant diagnostic difference between AN(BP) and BN is weight with people with AN being less than 85% of their ideal weight ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "American Psychiatric Association", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "edition" : "5", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "American Psychiatric Association", "publisher-place" : "Arlington, Virginia", "title" : "Diagnostic and statistical manual of mental disorders", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(American Psychiatric Association 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(American Psychiatric Association 2013). However, this theory ignores that binge eating is seen outside of the context of AN in both BN and BED and that some people with AN(R) do not cross-over to AN(BP) during the duration of their disease.5.6.2 Accumulation of independent genes leading to binge eating and Anorexia NervosaTaking into account the limitations of the previous theory as to why binge/purging behaviour coexists with AN, we have hypothesized that it is possible that independent genes lead to the binge/purging behaviour seen in BN and the extreme weight loss seen in AN. Through random segregation within populations, it is possible that some people cumulate both the genes predisposing to AN and the genes predisposing to BN. This theory is unlikely though because both AN and BN are relatively rare diseases. Using an estimated prevalence of 0.3 to 3.0% of AN in females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.maturitas.2013.04.014", "ISSN" : "1873-4111", "PMID" : "23706279", "abstract" : "Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed.", "author" : [ { "dropping-particle" : "", "family" : "Meczekalski", "given" : "Blazej", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Podfigurna-Stopa", "given" : "Agnieszka", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Katulski", "given" : "Krzysztof", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Maturitas", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "7" ] ] }, "page" : "215-220", "publisher" : "Elsevier Ireland Ltd", "title" : "Long-term consequences of anorexia nervosa", "type" : "article-journal", "volume" : "75" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-4", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1002/eat.parative", "author" : [ { "dropping-particle" : "", "family" : "Marques", "given" : "Luana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alegria", "given" : "Margarita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Becker", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chen", "given" : "Chih-nan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fang", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chosak", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Belo Diniz", "given" : "Juliana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "International Journal of Eating Disorders", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "412-420", "title" : "Comparative prevalence, correlates of impairment, and service utilization for eating disorders across U.S. ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders", "type" : "article-journal", "volume" : "44" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.appet.2013.01.005", "ISSN" : "1095-8304", "PMID" : "23348361", "abstract" : "During the last 25 years, the careful examination of the eating behavior of individuals with eating disorders has provided critical insights into the nature of these disorders. Crucially, studies investigating components of different eating behaviors have documented that Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED) are characterized by objective disturbances in eating patterns that are significantly different than behaviors exhibited by individuals who do not have these eating disorders. The detailed description of the disturbances in eating behavior has helped to identify diagnostic criteria associated with each disorder, and has led to important hypotheses about the underlying pathophysiology. These advances in understanding have provided, and continue to provide, a foundation for translational research and for the development of novel treatment interventions. This review is based on a presentation given by B. Timothy Walsh, M.D. at the 40th anniversary symposium of the Columbia University Appetite talks outlining the evolution of the discovery of the characteristic eating disturbances seen with each disorder.", "author" : [ { "dropping-particle" : "", "family" : "Heaner", "given" : "Martica K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walsh", "given" : "B Timothy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Appetite", "id" : "ITEM-6", "issued" : { "date-parts" : [ [ "2013", "6" ] ] }, "page" : "185-188", "publisher" : "Elsevier Ltd", "title" : "A history of the identification of the characteristics eating disturbances of bulimia nervosa, binge eating disorders and anorexia nervosa", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-7", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1192/bjp.186.2.132", "ISSN" : "0007-1250", "PMID" : "15684236", "abstract" : "BACKGROUND: During the years 1988-1993 the primary care incidence of anorexia nervosa in the UK remained stable, but the incidence of bulimia nervosa increased threefold. AIMS: To determine whether the incidence of anorexia nervosa remained stable, and that of bulimia nervosa continued to increase, in the years 1994-2000. METHOD: The General Practice Research Database was screened for new cases of anorexia and bulimia nervosa between 1994 and 2000. Annual incidence rates were calculated for females aged 10-39 years and compared with rates from the previous 5 years. RESULTS: In 2000 primary care incidence rates were 4.7 and 6.6 per 100,000 population for anorexia and bulimia nervosa, respectively. The incidence of anorexia nervosa remained remarkably consistent over the period studied. Overall there was an increase in the incidence of bulimia, but rates declined after a peak in 1996. CONCLUSIONS: This study provides further evidence for the stability of anorexia nervosa incidence rates. Decreased symptom recognition and changes in service use might have contributed to observed changes in the incidence of bulimia nervosa.", "author" : [ { "dropping-particle" : "", "family" : "Currin", "given" : "Laura", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schmidt", "given" : "Ulrike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Treasure", "given" : "Janet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jick", "given" : "Hershel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The British Journal of Psychiatry", "id" : "ITEM-8", "issued" : { "date-parts" : [ [ "2005", "2" ] ] }, "page" : "132-135", "title" : "Time trends in eating disorder incidence", "type" : "article-journal", "volume" : "186" }, "uris" : [ "" ] }, { "id" : "ITEM-9", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-9", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-10", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-10", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Favaro et al. 2003; Hoek and van Hoeken 2003; Currin et al. 2005; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Favaro et al. 2003; Hoek and van Hoeken 2003; Currin et al. 2005; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Preti et al. 2009; Marques et al. 2011; Heaner and Walsh 2013; Meczekalski et al. 2013) and estimated prevalence of 0.88 to 4.6% for BN in females ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s11920-012-0282-y", "ISSN" : "1535-1645", "PMID" : "22644309", "abstract" : "Eating disorders are relatively rare among the general population. This review discusses the literature on the incidence, prevalence and mortality rates of eating disorders. We searched online Medline/Pubmed, Embase and PsycINFO databases for articles published in English using several keyterms relating to eating disorders and epidemiology. Anorexia nervosa is relatively common among young women. While the overall incidence rate remained stable over the past decades, there has been an increase in the high risk-group of 15-19 year old girls. It is unclear whether this reflects earlier detection of anorexia nervosa cases or an earlier age at onset. The occurrence of bulimia nervosa might have decreased since the early nineties of the last century. All eating disorders have an elevated mortality risk; anorexia nervosa the most striking. Compared with the other eating disorders, binge eating disorder is more common among males and older individuals.", "author" : [ { "dropping-particle" : "", "family" : "Smink", "given" : "Fr\u00e9d\u00e9rique R E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Psychiatry Reports", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "406-414", "title" : "Epidemiology of eating disorders: incidence, prevalence and mortality rates", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Hudson", "given" : "James I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hiripi", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jr", "given" : "Harrison G Pope", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kessler", "given" : "Ronald C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Psychiatry", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "348-358", "title" : "The prevalence and correlates of eating disorders in the National Comorbidity Survey replication", "type" : "article-journal", "volume" : "61" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1097/01.yco.0000228759.95237.78", "ISSN" : "0951-7367", "PMID" : "16721169", "abstract" : "PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent literature on the incidence and prevalence of and mortality associated with eating disorders. RECENT FINDINGS: General-practice studies show that the overall incidence rates of anorexia nervosa remained stable during the 1990s, compared with the 1980s. Some evidence suggests that the occurrence of bulimia nervosa is decreasing. Anorexia nervosa is a common disorder among young white females, but is extremely rare among black females. Recent studies confirm previous findings of the high mortality rate within the anorexia nervosa population. SUMMARY: The incidence of anorexia nervosa is around eight per 100,000 persons per year. An upward trend has been observed in the incidence of anorexia nervosa in the past century till the 1970s. The most substantial increase was among females aged 15-24 years, for whom a significant increase was observed from 1935 to 1999. The average prevalence rates for anorexia nervosa and bulimia nervosa among young females are 0.3 and 1%, respectively. Only a minority of people with eating disorders, especially with bulimia nervosa, are treated in mental healthcare.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Current Opinion in Psychiatry", "id" : "ITEM-3", "issue" : "4", "issued" : { "date-parts" : [ [ "2006", "7" ] ] }, "page" : "389-394", "title" : "Incidence, prevalence and mortality of anorexia nervosa and other eating disorders", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01758.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wade", "given" : "Tracey D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bergin", "given" : "Jacqueline L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tiggemann", "given" : "Marika", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "Cynthia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "Christopher G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-4", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "121-128", "title" : "Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1017/S0033291708003942", "ISBN" : "0033291708003", "ISSN" : "0033-2917", "PMID" : "18775085", "abstract" : "BACKGROUND: Little is known about the epidemiology of bulimia nervosa outside clinical settings. We report the incidence, prevalence and outcomes of bulimia nervosa using for the first time a nationwide study design. METHOD: To assess the incidence and natural course and outcomes of DSM-IV bulimia nervosa among women from the general population, women (n=2881) from the 1975-79 birth cohorts of Finnish twins were screened for lifetime eating disorders using a two-stage procedure consisting of a questionnaire screen and the Structured Clinical Interview for DSM-IV (SCID). Clinical recovery was defined as 1-year abstinence from bingeing and purging combined with a body mass index (BMI) 19 kg/m2. RESULTS: The lifetime prevalence of DSM-IV bulimia nervosa was 2.3%; 76% of the women suffered from its purging subtype and 24% from the non-purging subtype. The incidence rate of bulimia nervosa was 300/100000 person-years at the peak age of incidence, 16-20 years, and 150/100000 at 10-24 years. The 5-year clinical recovery rate was 55.0%. Less than a third of the cases had been detected by health-care professionals; detection did not influence outcome. After clinical recovery from bulimia nervosa, the mean levels of residual psychological symptoms gradually decreased over time but many women continued to experience significantly more body image problems and psychosomatic symptoms than never-ill women. CONCLUSIONS: Few women with bulimia nervosa are recognized in health-care settings. Symptoms of bulimia are relatively long-standing, and recovery is gradual. Many clinically recovered women experience residual psychological symptoms after attaining abstinence from bingeing and purging.", "author" : [ { "dropping-particle" : "", "family" : "Keski-Rahkonen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoek", "given" : "H W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Linna", "given" : "M S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raevuori", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sihvola", "given" : "E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulik", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rissanen", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kaprio", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Medicine", "id" : "ITEM-5", "issue" : "5", "issued" : { "date-parts" : [ [ "2009", "5" ] ] }, "page" : "823-831", "title" : "Incidence and outcomes of bulimia nervosa: a nationwide population-based study", "type" : "article-journal", "volume" : "39" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/j.jpsychires.2009.04.003", "ISSN" : "1879-1379", "PMID" : "19427647", "abstract" : "Few data are available to estimate the prevalence of eating disorders (EDs) and their correlates in the community. This paper reports data on EDs obtained in the framework of the ESEMeD project, aimed at investigating the prevalence of non-psychotic mental disorders in six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain), using a new version of the Composite International Diagnostic Interview. The ESEMeD study was a general population cross-sectional household survey. In total, 21,425 respondents aged 18 or older provided data for the project between January 2001 and August 2003. A subsample (N=4139) underwent a detailed investigation on EDs. Lifetime estimated prevalence of anorexia nervosa, bulimia nervosa, binge eating disorder, sub-threshold binge eating disorder, and any binge eating were 0.48%, 0.51%, 1.12%, 0.72%, and 2.15%, respectively, and they were 3-8 times higher among women for all EDs. However, since people under 18 were excluded from this study, our prevalence should be taken as lower-bound estimate of real frequencies. Indeed, cumulative lifetime prevalence analysis showed that the majority of eating disorders had their initial onset between 10 and 20 years of age. Role impairment and comorbidity with other mental disorders were highly common, yet only small proportions of patients with a lifetime diagnosis of EDs requested medical treatment. It still has to be proven whether early diagnostic identification and access to specialized care can reduce the burden caused by these disorders.", "author" : [ { "dropping-particle" : "", "family" : "Preti", "given" : "Antonio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Girolamo", "given" : "Giovanni", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vilagut", "given" : "Gemma", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alonso", "given" : "Jordi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "De", "family" : "Graaf", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bruffaerts", "given" : "Ronny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Demyttenaere", "given" : "Koen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinto-Meza", "given" : "Alejandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haro", "given" : "Josep Maria", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosini", "given" : "Piero", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric Research", "id" : "ITEM-6", "issue" : "14", "issued" : { "date-parts" : [ [ "2009", "9" ] ] }, "page" : "1125-1132", "publisher" : "Elsevier Ltd", "title" : "The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] }, { "id" : "ITEM-7", "itemData" : { "DOI" : "10.1002/eat.10222", "ISSN" : "0276-3478", "PMID" : "14566926", "abstract" : "OBJECTIVE: To review the literature on the incidence and prevalence of eating disorders.\n\nMETHODS: We searched Medline using several key terms relating to epidemiology and eating disorders and we checked the reference lists of the articles that we found. Special attention has been paid to methodologic problems affecting the selection of populations under study and the identification of cases.\n\nRESULTS: An average prevalence rate for anorexia nervosa of 0.3% was found for young females. The prevalence rates for bulimia nervosa were 1% and 0.1% for young women and young men, respectively. The estimated prevalence of binge eating disorder is at least 1%. The incidence of anorexia nervosa is 8 cases per 100,000 population per year and the incidence of bulimia nervosa is 12 cases per 100,000 population per year. The incidence of anorexia nervosa increased over the past century, until the 1970s.\n\nDISCUSSION: Only a minority of people who meet stringent diagnostic criteria for eating disorders are seen in mental health care.", "author" : [ { "dropping-particle" : "", "family" : "Hoek", "given" : "Hans Wijbrand", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoeken", "given" : "Daphne", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "The International journal of eating disorders", "id" : "ITEM-7", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "12" ] ] }, "page" : "383-96", "title" : "Review of the prevalence and incidence of eating disorders.", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-8", "itemData" : { "DOI" : "10.1097/01.PSY.0000073871.67679.D8", "ISSN" : "0033-3174", "author" : [ { "dropping-particle" : "", "family" : "Favaro", "given" : "Angela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ferrara", "given" : "Silvia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Santonastaso", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychosomatic Medicine", "id" : "ITEM-8", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "7", "1" ] ] }, "page" : "701-708", "title" : "The spectrum of eating disorders in young women: A prevalence study in a general population sample", "type" : "article-journal", "volume" : "65" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Favaro et al. 2003; Hoek and van Hoeken 2003; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Keski-Rahkonen et al. 2009; Preti et al. 2009; Smink et al. 2012)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Favaro et al. 2003; Hoek and van Hoeken 2003; Hoek 2006; Wade et al. 2006; Hudson et al. 2008; Keski-Rahkonen et al. 2009; Preti et al. 2009; Smink et al. 2012), the prevalence of both AN and BN, therefore the AN(BP) subtype should be between 0.0026 and 0.138% while the actual prevalence of AN(BP) is likely somewhere between 0.15 to 1.5% of women based on half of the people with AN having the binge/purge subtype ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1176/appi.ajp.2007.07060951.Diagnostic", "author" : [ { "dropping-particle" : "", "family" : "Eddy", "given" : "Kamryn T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorer", "given" : "David J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franko", "given" : "Debra L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tahilani", "given" : "Kavita", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thompson-Brenner", "given" : "Heather", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herzog", "given" : "David B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Psychiatry", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "245-250", "title" : "Diagnostic crossover in Anorexia Nervosa and Bulimia Nerovsa: implications for the DSM-V", "type" : "article-journal", "volume" : "165" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Eddy et al. 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Eddy et al. 2013). Therefore, we can conclude that because the actual prevalence of AN(BP) is higher than would be expected from accumulation of independent genes leading to BN and AN, the genes associated with the individual diseases are either in linkage disequilibrium or the same genes are causing the two different diseases. 5.6.3 Mutations/structural gene variants with opposite effects in the same gene lead to AN or BNThe theory that the accumulation of independent genes causing binging behaviour and extreme weight loss explain the cross-over of diagnostic criteria in eating disorders is likely incorrect based on the much higher prevalence of AN(BP) in the population compared to theoretical prevalence of the genes crossing over. As discussed in the evolutionary theories section, the ability to consume large amounts of food when readily available may have been advantageous leading to the selection of genes that now promote binge eating in the modern food abundant environment ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "V", "family" : "Neel", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nutrition Reviews", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1999" ] ] }, "page" : "S2-S7", "title" : "The thrifty genotype in 1998", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "V", "family" : "Neel", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Human Genetics", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "1962" ] ] }, "page" : "353-362", "title" : "Diabetes mellitus: a \"thrifty\" genotype rendered detrimental by \"progress\"", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1017/S1464793105006974", "ISSN" : "1464-7931", "PMID" : "16677431", "abstract" : "Human susceptibility to obesity is an unusual phenomenon amongst animals. An evolutionary analysis, identifying factors favouring the capacity for fat deposition, may aid in the development of preventive public health strategies. This article considers the proximate causes, ontogeny, fitness value and evolutionary history of human fat deposition. Proximate causes include diet composition, physical activity level, feeding behaviour, endocrine and genetic factors, psychological traits, and exposure to broader environmental factors. Fat deposition peaks during late gestation and early infancy, and again during adolescence in females. As in other species, human fat stores not only buffer malnutrition, but also regulate reproduction and immune function, and are subject to sexual selection. Nevertheless, our characteristic ontogenetic pattern of fat deposition, along with relatively high fatness in adulthood, contrasts with the phenotype of other mammals occupying the tropical savannah environment in which hominids evolved. The increased value of energy stores in our species can be attributed to factors increasing either uncertainty in energy availability, or vulnerability to that uncertainty. Early hominid evolution was characterised by adaptation to a more seasonal environment, when selection would have favoured general thriftiness. The evolution of the large expensive brain in the genus Homo then favoured increased energy stores in the reproducing female, and in the offspring in early life. More recently, the introduction of agriculture has had three significant effects: exposure to regular famine; adaptation to a variety of local niches favouring population-specific adaptations; and the development of social hierarchies which predispose to differential exposure to environmental pressures. Thus, humans have persistently encountered greater energy stress than that experienced by their closest living relatives during recent evolution. The capacity to accumulate fat has therefore been a major adaptive feature of our species, but is now increasingly maladaptive in the modern environment where fluctuations in energy supply have been minimised, and productivity is dependent on mechanisation rather than physical effort. Alterations to the obesogenic environment are predicted to play a key role in reducing the prevalence of obesity.", "author" : [ { "dropping-particle" : "", "family" : "Wells", "given" : "Jonathan C K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological Reviews", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2006", "5" ] ] }, "page" : "183-205", "title" : "The evolution of human fatness and susceptibility to obesity: an ethological approach", "type" : "article-journal", "volume" : "81" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1080/j.1440-1614.2006.01903.x", "ISSN" : "0004-8674", "author" : [ { "dropping-particle" : "", "family" : "Wells", "given" : "J. Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oakley Browne", "given" : "Mark a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "Kate M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McGee", "given" : "Magnus a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baxter", "given" : "Joanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kokaua", "given" : "Jesse", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Australian and New Zealand Journal of Psychiatry", "id" : "ITEM-4", "issue" : "10", "issued" : { "date-parts" : [ [ "2006", "1" ] ] }, "page" : "845-854", "title" : "Prevalence, interference with life and severity of 12 month DSM-IV disorders in Te Rau Hinengaro: The New Zealand Mental Health Survey", "type" : "article-journal", "volume" : "40" }, "uris" : [ "" ] }, { "id" : "ITEM-5", "itemData" : { "DOI" : "10.1016/j.psc.2011.08.005", "ISSN" : "1558-3147", "PMID" : "22098799", "abstract" : "The obesity epidemic in the United States has proven difficult to reverse. We have not been successful in helping people sustain the eating and physical activity patterns that are needed to maintain a healthy body weight. There is growing recognition that we will not be able to sustain healthy lifestyles until we are able to address the environment and culture that currently support unhealthy lifestyles. Addressing obesity requires an understanding of energy balance. From an energy balance approach it should be easier to prevent obesity than to reverse it. Further, from an energy balance point of view, it may not be possible to solve the problem by focusing on food alone. Currently, energy requirements of much of the population may be below the level of energy intake than can reasonably be maintained over time. Many initiatives are underway to revise how we build our communities, the ways we produce and market our foods, and the ways we inadvertently promote sedentary behavior. Efforts are underway to prevent obesity in schools, worksites, and communities. It is probably too early to evaluate these efforts, but there have been no large-scale successes in preventing obesity to date. There is reason to be optimistic about dealing with obesity. We have successfully addressed many previous threats to public health. It was probably inconceivable in the 1950s to think that major public health initiatives could have such a dramatic effect on reducing the prevalence of smoking in the United States. Yet, this serious problem was addressed via a combination of strategies involving public health, economics, political advocacy, behavioral change, and environmental change. Similarly, Americans have been persuaded to use seat belts and recycle, addressing two other challenges to public health. But, there is also reason to be pessimistic. Certainly, we can learn from our previous efforts for social change, but we must realize that our challenge with obesity may be greater. In the other examples cited, we had clear goals in mind. Our goals were to stop smoking, increase the use of seatbelts, and increase recycling. The difficulty of achieving these goals should not be minimized, but they were clear and simple goals. In the case of obesity, there is no clear agreement about goals. Moreover, experts do not agree on which strategies should be implemented on a widespread basis to achieve the behavioral changes in the population needed to reverse the high prevalence rates o\u2026", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Nia S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Catenacci", "given" : "Victoria a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wyatt", "given" : "Holly R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hill", "given" : "James O", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The Psychiatric Clinics of North America", "id" : "ITEM-5", "issue" : "4", "issued" : { "date-parts" : [ [ "2011", "12" ] ] }, "page" : "717-732", "publisher" : "Elsevier Inc.", "title" : "Obesity: overview of an epidemic", "type" : "article-journal", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-6", "itemData" : { "DOI" : "10.1016/S0140-6736(11)60813-1", "ISSN" : "1474-547X", "PMID" : "21872749", "abstract" : "The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers.", "author" : [ { "dropping-particle" : "", "family" : "Swinburn", "given" : "Boyd a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sacks", "given" : "Gary", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hall", "given" : "Kevin D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McPherson", "given" : "Klim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finegood", "given" : "Diane T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moodie", "given" : "Marjory L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gortmaker", "given" : "Steven L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Lancet", "id" : "ITEM-6", "issue" : "9793", "issued" : { "date-parts" : [ [ "2011", "8", "27" ] ] }, "page" : "804-814", "publisher" : "Elsevier Ltd", "title" : "The global obesity pandemic: shaped by global drivers and local environments", "type" : "article-journal", "volume" : "378" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Neel 1962, 1999; Wells 2006; Wells et al. 2006; Mitchell et al. 2011; Swinburn et al. 2011)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Neel 1962, 1999; Wells 2006; Wells et al. 2006; Mitchell et al. 2011; Swinburn et al. 2011). The ability to also be highly functioning with minimal caloric intake may also have been beneficial as it would enable migration from food insecure areas to more food secure areas promoting genes that may now lead to what is known as AN ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/0033-295X.110.4.745", "ISSN" : "0033-295X", "PMID" : "14599241", "abstract" : "Anorexia nervosa (AN) is commonly attributed to psychological conflicts, attempts to be fashionably slender, neuroendocrine dysfunction, or some combination of these factors. Considerable research reveals these theories to be incomplete. Psychological and societal factors account for the decision to diet but not for the phenomenology of the disorder; theories of biological defects fail to explain neuroendocrine findings that suggest coordinated physiological mechanisms. This article presents evidence that AN's distinctive symptoms of restricting food, denial of starvation, and hyperactivity are likely to be evolved adaptive mechanisms that facilitated ancestral nomadic foragers leaving depleted environments; genetically susceptible individuals who lose too much weight may trigger these archaic adaptations. This hypothesis accounts for the occurrence of AN-like syndromes in both humans and animals and is consistent with changes observed in the physiology, cognitions, and behavior of patients with AN.", "author" : [ { "dropping-particle" : "", "family" : "Guisinger", "given" : "Shan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Psychological Review", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2003", "10" ] ] }, "page" : "745-761", "title" : "Adapted to flee famine: adding an evolutionary perspective on anorexia nervosa", "type" : "article-journal", "volume" : "110" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.mehy.2013.12.003", "ISSN" : "1532-2777", "PMID" : "24373562", "abstract" : "Anorexia nervosa is a puzzling and often tragic disorder which causes the individual to self starve and hyper-exercise. We present a speculative analysis of the disorder which begins by acknowledging and accepting the adaptation to flee famine theory. This theory holds that anorexia nervosa results from activation of an archaic pathway that functioned well during human's nomadic past. We advance this idea by suggesting that the faulty signal indicating there is a famine, arises from misalignment of the circadian/circannual oscillations. Entry and exit from hibernation is dependent on these cycles, and we draw an analogy between hibernation and anorexia nervosa. We offer ideas for testing the hypothesis, and targeting these faulty signals.", "author" : [ { "dropping-particle" : "", "family" : "Scolnick", "given" : "Barbara", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mostofsky", "given" : "David I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Hypotheses", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2014", "2" ] ] }, "page" : "231-235", "publisher" : "Elsevier Ltd", "title" : "Anorexia nervosa: A rogue hibernation?", "type" : "article-journal", "volume" : "82" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Guisinger 2003; Scolnick and Mostofsky 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Guisinger 2003; Scolnick and Mostofsky 2014). It is possible that mutations or structural variants such as deletion/duplication, gain of function/loss of function, gain of expression/loss of expression in the same genes may lead to AN and binging behaviour. This ties in with the evolutionary theories as these genes may have been positively selected for in the past under different environmental conditions and people with both types of mutations may have been favoured. This could lead to partial linkage disequilibrium between mutations in the population, leading to the high prevalence of the mixed phenotypes. In the past, people possessing both the loss of function and gain of function mutations may not have suffered from any negative side effects allowing for the transmission of the genes on to future generations. It is feasible that the mixed phenotypes are now only problematic in the obesogenic environment. Weight concerns are a relatively modern concept and dieting to lose weight could trigger the metabolic changes allowing for survival despite low caloric consumption. However, if the same genes are also causing binging behaviour, individuals may purge in order to balance the conflicting biological drives to survive with minimal caloric consumption and to take advantage of the food available to them. The possibility of a single gene having both loss of function and gain of function mutations is supported by recent findings on MC4R and the 16p locus where deletion/loss of function mutations lead to hyperphagic obesity while duplications/gain of function mutations lead to leanness and food-related phenotypes ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1086/382490", "ISSN" : "0002-9297", "PMID" : "14973783", "abstract" : "Several rare mutations in the melanocortin-4 receptor gene (MC4R) predispose to obesity. For the most common missense variant V103I (rs2229616), however, the previously reported similar carrier frequencies in obese and nonobese individuals are in line with in vitro studies, which have not shown a functional implication of this variant. In the present study, we initially performed a transmission/disequilibrium test on 520 trios with obesity, and we observed a lower transmission rate of the I103 allele (P=.017), which was an unexpected finding. Therefore, we initiated two large case-control studies (N=2,334 and N=661) and combined the data with those from 12 published studies, for a total of 7,713 individuals. The resulting meta-analysis provides evidence for a negative association of the I103 allele with obesity (odds ratio 0.69; 95% confidence interval 0.50-0.96; P=.03), mainly comprising samples of European origin. Additional screening of four other ethnic groups showed comparable I103 carrier frequencies well below 10%. Genomic sequencing of the MC4R gene revealed three polymorphisms in the noncoding region that displayed strong linkage disequilibrium with V103I. In our functional in vitro assays, the variant was indistinguishable from the wild-type allele, as was the result in previous studies. This report on an SNP/haplotype that is negatively associated with obesity expands the successful application of meta-analysis of modest effects in common diseases to a variant with a carrier frequency well below 10%. The respective protective effect against obesity implies that variation in the MC4R gene entails both loss and gain of function.", "author" : [ { "dropping-particle" : "", "family" : "Geller", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reichwald", "given" : "Kathrin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dempfle", "given" : "Astrid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Illig", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vollmert", "given" : "Caren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herpertz", "given" : "Stephan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siffert", "given" : "Winfried", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Platzer", "given" : "Matthias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hess", "given" : "Claudia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gudermann", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Biebermann", "given" : "Heike", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wichmann", "given" : "H-Erich", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sch\u00e4fer", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hinney", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hebebrand", "given" : "Johannes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American journal of human genetics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2004", "3" ] ] }, "page" : "572-81", "title" : "Melanocortin-4 receptor gene variant I103 is negatively associated with obesity.", "type" : "article-journal", "volume" : "74" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Geller et al. 2004)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Geller et al. 2004). To test this hypothesis, a gene-level association using a whole-exome sequencing approach could be conducted in patients with AN(R), AN(BP), BN, BED, and healthy controls could be conducted. 5.6.4 Mutations in nearby genes result in partial linkage disequilibrium of Anorexia Nervosa and binge eating traitsSimilar to the theory that the same genes may contain loss of function/gain of function mutations causing the cross-over of traits seen in eating disorders is the theory that the genes coding for the different characteristics of eating disorders are in genes located near each other, 5.6.5 Summary of the role of genetics in the coexistence of Anorexia Nervosa and Bulimia Nervosa in binge/purge subtype Anorexia Nervosa We have proposed four theories for why there is an overlap of characteristics seen in AN(R), AN(BP), BN, and BED. Binge eating is used as a protective mechanism against starvation in people with AN who are not meeting their energy requirements AN(BP) occurs in individuals who have both the independent genes for AN and the independent genes for binge eating Mutations/structural gene variants with opposite effects in the same gene lead to AN or BNMutations in nearby genes result in partial disequilibrium of the genes for AN and the genes for binge eating causing a higher than expected number of people to display the mixed phenotype AN(BP) than would be expected if the genes were not in partial linkage disequilibrium We found that it is unlikely that that binge eating is purely a protective mechanism against AN because it doesn’t account for the high proportion of people who binge eat without having prior starvation as seen in BN and BED. We also discount the theory that AN(BP) occurs in individuals who have the genes for both AN(R) and binge eating as the prevalence of AN(BP) far surpasses what would be expected if the genes for AN(R) and binge eating are independent of each other. It is feasible that both mutations/structural gene variants in the same gene causing opposite effects and that mutations in nearby genes resulting in partial disequilibrium for the genes causing AN(R) and binge eating can explain the overlap of phenotypes seen in AN(BP). 5.7 Conclusions We combined the evolutionary perspective of eating disorders with the possibility of the genetic overlap causing mixed phenotypes, and the epidemiological evidence of differences in prevalence of eating disorders in different ethnicities and cultures to create a framework suggesting under which conditions each eating disorder will occur (Figure 4). In this framework, we propose that there are separate genes predisposing individuals to AN(R) and genes that predispose individuals to binge eating. These genes are likely to overlap because they are in partial linkage disequilibrium, either because mutations/structural variants within the same gene code for loss of function/gain of function mutations or because the genes are located close to each other. Therefore, a greater number of people would have characteristics of both diseases than would be expected if the genes were independent. Thus three genotypic categories were created, people with only AN(R) genes, people with only binge eating genes, and people with genes predisposing to both diseases. Another critical element of the framework is the differences in prevalence of the eating disorders seen in different cultures/ethnicities. Because of the challenges in untangling the effect of culture versus ethnicity it is impossible to determine how much of the between-ethnicity variability in the prevalence of eating disorders is attributable to genetics versus how much is attributable to culture. However, it is well established that White women are more concerned about weight have lower weight ideals in comparison to Black women ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0002-953X", "PMID" : "11532731", "abstract" : "OBJECTIVE: Binge eating disorder was introduced in DSM-IV as a psychiatric disorder needing further study. This community-based study describes the relationship between race and clinical functioning in black and white women with and without binge eating disorder. METHOD: A group of 150 women with binge eating disorder (52 black, 98 white) and a race-matched group of 150 healthy comparison subjects were recruited from the community. Eating and psychiatric symptoms were assessed through interviews and self-report. RESULTS: Black and white women with binge eating disorder differed significantly on numerous eating disorder features, including binge frequency, restraint, history of other eating disorders, treatment-seeking behavior, and concerns with eating, weight, and shape. Black and white healthy comparison subjects differed significantly in obesity rates. CONCLUSIONS: For both black and white women, binge eating disorder was associated with significant impairment in clinical functioning. Yet, racial differences in clinical presentation underscore the importance of considering race in psychopathology research.", "author" : [ { "dropping-particle" : "", "family" : "Pike", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dohm", "given" : "F a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Striegel-Moore", "given" : "R H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilfley", "given" : "D E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fairburn", "given" : "C G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Psychiatry", "id" : "ITEM-1", "issue" : "9", "issued" : { "date-parts" : [ [ "2001", "9" ] ] }, "page" : "1455-1460", "title" : "A comparison of black and white women with binge eating disorder", "type" : "article-journal", "volume" : "158" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "ISSN" : "1351-0126", "PMID" : "11896858", "abstract" : "Anorexia nervosa is currently considered a disorder confined to Western culture. Its recent identification in non-Western societies and different subcultures within the Western world has provoked a theory that Western cultural ideals of slimness and beauty have infiltrated these societies. The biomedical definition of anorexia nervosa emphasizes fat-phobia in the presentation of anorexia nervosa. However, evidence exists that suggests anorexia nevosa can exist without the Western fear of fatness and that this culturally biased view of anorexia nervosa may obscure health care professionals' understanding of a patient's own cultural reasons for self-starvation, and even hinder their recovery.", "author" : [ { "dropping-particle" : "", "family" : "Simpson", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Psychiatric and Mental Health Nursing", "id" : "ITEM-2", "issue" : "1", "issued" : { "date-parts" : [ [ "2002", "2" ] ] }, "page" : "65-71", "title" : "Anorexia nervosa and culture", "type" : "article-journal", "volume" : "9" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "ISSN" : "1471-0153", "PMID" : "15001011", "abstract" : "There is a growing literature on the relationship between race/ethnicity and body image and eating disorders, but the conclusions are still unclear. We therefore examined racial/ethnic influences on body image and eating behaviors in 108 Caucasian, 46 African American, and 40 Asian female undergraduates. Participants completed the Figure Rating Scale (FRS) and the Eating Habits Questionnaire (EHQ) to assess body image and eating pathology. Caucasians had greater body discrepancy (difference between current and ideal) than Asians (P=.05) and higher EHQ scores (P<.0001) than both Asians and African Americans. African Americans chose a larger ideal body size than the other groups (P=.005). However, Asian women had a significantly lower body mass index (BMI) than both groups (P<.0001). After controlling for BMI, ideal body size differences were minimized (P=.08). Also, now, both Caucasians and Asians had greater body discrepancy (P<.0001) and EHQ scores (P<.0001) than African Americans. Our findings help reconcile inconsistencies in the literature by demonstrating the impact of controlling for BMI when comparing body image and eating behaviors in individuals from different racial/ethnic backgrounds.", "author" : [ { "dropping-particle" : "", "family" : "Gluck", "given" : "Marci E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geliebter", "given" : "Allan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Eating Behaviors", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "1" ] ] }, "page" : "143-151", "title" : "Racial/ethnic differences in body image and eating behaviors", "type" : "article-journal", "volume" : "3" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Pike et al. 2001; Gluck and Geliebter 2002; Simpson 2002)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Pike et al. 2001; Gluck and Geliebter 2002; Simpson 2002) and it is very feasible that at least some of the greater prevalence of AN and BN in White females is because they feel an increased pressure to be thin. The pressure to be thin is not exclusively related to ethnicity and consequently in our framework we created a binary variable of either the presence or absence of pressure to be thin. The two independent variables consisting of the three genotypic groups and the presence or absence of the pressure to be thin create six categories. Individuals with only the genes predisposing to AN(R) will develop AN(R) if there is sufficient pressure to be thin using the elaboration of AFFH and rogue hibernation theories which indicate that dieting can cause the metabolic shift leading to the diseases. In the absence of weight concerns, an individual would not develop AN(R) despite having predisposing genes unless starvation was achieved through famine, fasting, or other non-weight related reasons why food consumption may be lowered. People with only the genes predisposing to binge eating in the presence of the pressure to be thin will be at risk for developing BN because genetically they are driven to eat however have a strong desire to maintain a normal weight and therefore use inappropriate compensatory behaviours. Without the pressure to maintain a certain weight, only BED will occur because the individual is not driven to compensate for the overconsumption of calories. For those with the mixed genotype, in the presence of having a weight preoccupation AN(BP) occurs because the individual cannot avoid binging on food, however is highly motivated to maintain a minimum weight and has the genetic advantage of being able to be functional despite their low energy intake. People with the mixed phenotype who do not feel pressure to be thin will be at increased risk for BED because they are driven to binge, yet do not feel the need to compensate for the overconsumption of calories. Genes predisposing to Anorexia Nervosa (restrictive subtype) Genes predisposing to AN (restrictive subtype) and genes predisposing to binge eating Genes predisposing to binge eating Presence of pressure to be thinAnorexia Nervosa (restrictive subtype)Anorexia Nervosa (binge/purge subtype)Bulimia NervosaAbsence of pressure to be thinNo disease – unless Anorexia Nervosa is triggered by factors other than weight loss, such as lack of food availability or fastingBinge Eating DisorderBinge Eating Disorderright180975Figure 4: Framework for the risk of developing an eating disorder based on genotypic category and presence or absence of pressure to be thin020000Figure 4: Framework for the risk of developing an eating disorder based on genotypic category and presence or absence of pressure to be thinThis framework provides a simplified view of the interaction of the potential genetics of eating disorders and the environment, specifically the pressure to be thin. There are many other factors that contribute to the risk of developing eating disorders not captured in the model such as epigenetics, gene by gene interactions, gene by environment interactions in addition to the pressure of being thin, any potential genetic factors which contribute to the predisposition of being more sensitive to the pressure of being thin, and a plethora of other environmental factors. 6.0 Ethical Considerations The investigation of genetic susceptibility of diseases and the subsequent research to determine the biological pathways through which the genes are functioning is working towards personalized medicine. The concept of personalized medicine involves using an individual’s unique genetics as well their life context to predict which diseases or medical conditions they will suffer from and ideally prevent the disease from occurring, as well as providing targeted treatment plans if a disease is not preventable ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1113/jphysiol.2014.272336", "ISSN" : "1469-7793", "PMID" : "24882820", "abstract" : "Ideas about personalized medicine are underpinned in part by evolutionary biology's Modern Synthesis. In this essay we link personalized medicine to the efforts of the early statistical investigators who quantified the heritability of human phenotype and then attempted to reconcile their observations with Mendelian genetics. As information about the heritability of common diseases was obtained, similar efforts were directed at understanding the genetic basis of disease phenotypes. These ideas were part of the rationale driving the Human Genome Project and subsequently the personalized medicine movement. In this context, we discuss: (1) the current state of the genotype-phenotype relationship in humans, (2) the common-disease-common-variant hypothesis, (3) the current ability of 'omic' information to inform clinical decision making, (4) emerging ideas about the therapeutic insight available from rare genetic variants, and (5) the social and behavioural barriers to the wider potential success of personalized medicine. There are significant gaps in knowledge as well as conceptual, intellectual, and philosophical limitations in each of these five areas. We then provide specific recommendations to mitigate these limitations and close by asking if it is time for the biomedical research community to 'stop chasing Mendel?'", "author" : [ { "dropping-particle" : "", "family" : "Joyner", "given" : "Michael J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prendergast", "given" : "Franklyn G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Physiol", "id" : "ITEM-1", "issue" : "11", "issued" : { "date-parts" : [ [ "2014", "6", "1" ] ] }, "page" : "2381-2388", "title" : "Chasing Mendel: five questions for personalized medicine", "type" : "article-journal", "volume" : "592" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Joyner and Prendergast 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Joyner and Prendergast 2014). Examples of genotyping being used to help health care practitioners decide on the treatment or management of disease exist today. Screening for the BRCA1 and BRCA2 genes in females with familial breast cancer allows for increased screening or preventative measures to be taken if necessary ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/path.4205", "ISSN" : "1096-9896", "PMID" : "23620175", "abstract" : "The discovery of the first major breast cancer susceptibility gene, BRCA1, occurred almost 20 years ago. BRCA1, together with BRCA2 remain the most important discoveries in human cancer genetics. Identification of highly penetrant mutations in these two tumour suppressor genes has had broad implications for women at risk and their families, for health professionals caring for these persons and for basic researchers. The BRCA proteins have many critical functions, the most notable of which, from a clinical perspective, is repair of double-strand DNA breaks.", "author" : [ { "dropping-particle" : "", "family" : "Foulkes", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shuen", "given" : "Andrew Y", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "J Pathol", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "8" ] ] }, "page" : "347-349", "title" : "In brief: BRCA1 and BRCA2.", "type" : "article-journal", "volume" : "230" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Foulkes and Shuen 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Foulkes and Shuen 2013). Phenylketonuria, an inability to convert phenylalanine to tyrosine caused by mutations in the gene encoding for phenylalanine hydroxylase can be detected by blood tests and genetic testing can confirm the diagnosis. If identified at birth, phenylketonuria can be effectively managed, however if not it causes severe mental retardation amongst other issues ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Spronsen", "given" : "Francjan J", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nat Rev Endrocrinol", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "509-514", "title" : "Phenylketonuria: a 21st century perspective", "type" : "article-journal", "volume" : "6" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(van Spronsen 2010)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(van Spronsen 2010). Despite the current successes using genetic information to improve human health, the ability to sequence the entire human genome has created an ethical debate about how to best protect the privacy of individuals who participate in genomic research ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3389/fgene.2014.00034", "ISSN" : "1664-8021", "PMID" : "24634673", "abstract" : "Prior to 1974, the Tuskegee Syphilis experiments, expansive use of the HeLa cells, and other blatant instances of research abuse pervaded the medical research field. Ongoing challenges to informed consent, privacy and data-sharing will influence the stories that research participants today share with future generations. This has significant implications for the advancement of genomic science, and the public's perception of genomic research.", "author" : [ { "dropping-particle" : "", "family" : "Callier", "given" : "Shawneequa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Husain", "given" : "Rajah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Simpson", "given" : "Rachel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Frontiers in Genetics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014", "1" ] ] }, "page" : "34", "title" : "Genomic data-sharing: what will be our legacy?", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Callier et al. 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Callier et al. 2014). A specific ethical consideration of genetic research is how to handle disclosure to the individual ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "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" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "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" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Li and Meyre 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Li and Meyre 2014)) and to the family ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/15265161.2013.828531", "ISSN" : "1536-0075", "PMID" : "24024818", "author" : [ { "dropping-particle" : "", "family" : "Rothstein", "given" : "Mark a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Bioethics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "64-65", "title" : "Should researchers disclose results to descendants?", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rothstein 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rothstein 2013). Telling an individual that they have an increased risk for a medical condition, particularly one for which preventative measures or treatments may be unavailable could cause the participant stress. On the other hand, knowing about late onset, non-preventable diseases may allow people to plan reproductive decisions and finances accordingly ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "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" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "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" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Li and Meyre 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Li and Meyre 2014). However, not telling participants if they are at risk could also be ethically unsound because of an individual’s right to know that information and take whatever actions they see fit. More complicated is if an individual involved in a study is found to have a genetic disorder that could be passed on to their family. In some cases the participant may be contacted to determine if they would like to tell family members but in cases where the participant has passed away, an ethical dilemma occurs. There are no current guidelines indicating if disclosing the information to the family is legal, ethical, or what the consequences could be ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/15265161.2013.828531", "ISSN" : "1536-0075", "PMID" : "24024818", "author" : [ { "dropping-particle" : "", "family" : "Rothstein", "given" : "Mark a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Bioethics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "64-65", "title" : "Should researchers disclose results to descendants?", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rothstein 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rothstein 2013). Researchers can in part avoid this situation by asking about the release of information to family members in life and in death on the consent form, however in participants who do not want the information shared, there can still be an ethical dilemma if the lives of family members could be saved by knowing the information ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1080/15265161.2013.828531", "ISSN" : "1536-0075", "PMID" : "24024818", "author" : [ { "dropping-particle" : "", "family" : "Rothstein", "given" : "Mark a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "The American Journal of Bioethics", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013", "1" ] ] }, "page" : "64-65", "title" : "Should researchers disclose results to descendants?", "type" : "article-journal", "volume" : "13" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Rothstein 2013)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Rothstein 2013). Beyond the concerns of how genetic information can be used, there are also issues about for whom genetic testing will be available. The cost to sequence the whole human genome has rapidly dropped from approximately $2.7 billion for the first genome sequenced to $5000 in June 2013. As genetic testing becomes more affordable, physicians will need to start determining who needs genetic testing versus which individuals it is medically unnecessary for to avoid using health care dollars inappropriately. Another consequence of the increasing affordability of genetic testing is that individuals can seek out private testing. This could create system in which people of higher socioeconomic status could be in a position to receive better health care. However, the traditional health care system has not yet fully transitioned to genomic medicine and only 10% of American doctors feel comfortable using approved genetic tests. Though patients want doctors to interpret their genetic testing results, many of them also do not feel that doctors are sufficiently trained to do the task. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "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" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "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" }, "uris" : [ "" ] } ], "mendeley" : { "previouslyFormattedCitation" : "(Li and Meyre 2014)" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }(Li and Meyre 2014). Specific to the research included in this thesis, the only ethical consideration is keeping the data collected from participants confidential which has been built into the study design of EpiDREAM. The EpiDREAM study was approved by the local ethics committee and informed consent was obtained from each subject before participating in the study, in accordance with the Declaration of Helsinki. The individual and collective effect size of obesity predisposing genes on obesity and food consumption patterns is extremely modest. Therefore, the conclusions of this study while supporting the role of genetics in obesity risk also are not significant enough to warrant telling participants or their families about their slightly enhanced risk for obesity. As the field of personalized medicine advances forward and genetic testing becomes more frequent, it is important that guidelines for both research and clinical applications are developed to take the advancements into consideration. For genetics research, it is especially important to determine what results will be passed on to the participants and/or their families and to have this information included as part of the informed consent process. Continued guideline development will be necessary protect individuals from genetic discrimination from insurance companies or potential employers and what information from genetic testing should be provided to individuals and their families. For clinical applications, there will need to be a sufficient number of genetic counsellors available, or extra training provided to relevant physicians, to discuss the implications of the results of the genetic testing. 7.0 Conclusions and Future Work The first half of this thesis focused on the association of 14 obesity predisposing SNPs and a gene score with dietary consumption parameters including daily intakes of total energy, total fat, saturated fat, trans fat, monounsaturated fat, polyunsaturated fat, carbohydrates and protein. Our results confirmed the positive association of two of the obesity predisposing SNPs as well as the gene score with BMI. Adjusting for energy did not significantly change the association, indicating that these SNPs are associated with BMI independent of how much food is consumed, supporting that an increase in energy consumption is not the only biological mechanism leading to obesity. We also found statistically significant relationships between six of the obesity predisposing SNPs and the gene score with at least one energy adjusted dietary parameter, specifically with total energy, total fat, and subcategories of fat. Adjusting these relationships for BMI did not significantly attenuate the relationships demonstrating that participants were not consuming more energy or having higher fat diets because of their increased weight. The most significant finding was the novel association of two separate SNPs located in or near BDNF (rs6265 and rs1401635) with total fat, MUFA, and PUFA intake, with rs1401635 also being associated with total energy and trans fat intake. Biological support of the relationship comes from the role of BDNF in monogenic forms of obesity which are characterized by hyperphagia and mouse models in which dietary fat moderates the relationship between mice with BDNF mutations and hyperphagia. The association of rs6235 (PCSK1) and the genotype score with total energy intake were similarly novel with biological evidence supporting PCSK1 because it is also a gene affiliated with monogenic forms of obesity and that a total PCSK1 deficiency leads to extreme hyperphagia. The second half of this thesis discussed the evolutionary history of eating disorders. Using current epidemiological evidence, we propose that the AFFH best explains AN because it takes into account the weight loss element, increased energy expenditure, and ethnic/cultural differences observed in people with AN. Theories involving suppression of reproduction and sexual competition do not take the increased energy expenditure into account. The sexual competition theories have a further flaw as they indicate that often it is older females who attempt to lose weight to compete with younger females. However, eating disorders, particularly AN are much more prevalent in young females compared to old females. Furthermore, the suppression of fertility that can occur with severe eating disorders does not account for the high heritability of the diseases as those with supressed reproduction would have a less opportunity to reproduce and pass on the genes.We also propose that BN and BED may not be distinct diseases but instead categories of the same disease. Historically, a drive to consume food when available may have been protective during times of food scarcity, however in today’s calorie abundant environment it is an undesirable trait. Both BN and BED feature binge eating as a diagnostic criteria. People with BN use inappropriate compensatory behaviours, often purging, after binges and people with BED do not use inappropriate compensatory behaviours. Evidence that BED and BN have the same basic cause comes from the ethnic differences. The prevalence of BED is relatively equal across ethnicities whereas BN is mostly seen in Western cultures where thinness is idealized. Therefore it could be the socially constructed strive for thinness causing the purging, rather than a unique genetic determinant. The much higher prevalence of AN in Western cultures may also be explained by environmental factors encouraging the drive for thinness. The AFFH does not involve the preoccupation with food which is now part of the AN diagnostic criteria, but instead proposes that the metabolic changes seen in AN came about because of food scarcity. Voluntary food restriction in the form of dieting because of a preoccupation with weight may trigger the same biological response. Together, the two components of this thesis provide evidence supporting that obesity and disordered eating patterns have a strong genetic basis. However, both sections also indicate that there is a need to widen the scope of biological mechanisms and genes being investigated in the context of obesity and eating disorders. Most research conducted in obesity promoting SNPs is focused on excessive energy intake, however the lack of association of most of the obesity promoting SNPs and the modest association of the gene score with energy consumption point to alternative biological mechanisms, such as alterations in metabolism. Despite the high likelihood that there are genetically linked features other than food consumption that are associated with weight, there is still the need of adequately powered studies to confirm the currently known associations of obesity predisposing SNPs with food behaviour as well as detect unknown associations. Using novel populations such as obese people who are successfully losing weight through caloric restriction, or those who are gaining weight for GWAS may also help identify relevant genes. Having a better understanding of the behaviours that SNPs are modifying obesity through will help determine the specific biological pathways that are being impacted. This information will be crucial in the development of preventative strategies for obesity. Great strides have been made in conducting GWAS for obesity in ethnicities other than Europeans, however studies focusing on nutrient consumption patterns and other factors that could be causing obesity are still mostly limited to Europeans. The evidence indicates that some obesity predisposing genes are ethnicity specific. If the ultimate goal of understanding the genetics of obesity is to come up with strategies to avoid weight gain, researchers need to have the information required to create ethnic specific programs. As the field of obesity genetics grows, more emphasis will also need to be placed on understanding gene by gene interactions, gene by environment interactions, and epigenetics. Creating consortiums by pooling large amounts of genetic and phenotypic data from multiple research groups with help to facilitate this research by providing the sample sizes required to have adequately powered studies. To better understand the genetics of eating disorders, many critical questions need to be answered. Not specifically pertaining to genetics is the need for better phenotyping of eating disorders. In our review, we propose that weight preoccupation which is a requirement for the diagnosis of AN may not a relevant diagnostic criteria. Using the adapted to flee famine hypothesis, any food restriction could bring on the metabolic changes seen in AN. In Western cultures, dieting may be the most frequent and relevant instigator but evidence shows that AN occurs world wide, regardless of the idealization of thinness. To determine if the theory that the preoccupation with thinness is a Western ideal instead of an intrinsic part of eating disorders is correct, biochemical data including hormones, metabolites, transcription factors, and protein profiles should be compared between patients who present with all symptoms of AN except for a preoccupation with weight and patients who have all symptoms of AN including a preoccupation with weight. If the biochemical changes are similar in the two populations, this would indicate that the diagnostic criteria for AN should be broadened. While the treatment for people with and without weight occupations may be different, widening the diagnostic criteria may allow for more people in need to receive treatment. Similarly, more research is required to determine if purging, the only difference between BN and BED, is purely because of a desire to be thin, or if there are other biological mechanisms that induce purging. For genetic studies, the next step should be changing the focus from looking at genes associated with neuropeptides and hormones which may only be a symptom of the disease to looking at genes that are linked to metabolism. Small sample sizes are a significant problem in eating disorder research as many people attempt to hide the disease. Establishing clearer phenotypes and subdividing into categories such as people with AN who have weight preoccupations and those who do not have weight preoccupations could increase sample sizes as would collaborations. Because eating disorders are extreme abnormalities in eating patterns, if common gene variants are found to be associated with the diseases, then they are likely to be good candidate genes to investigate for obesity as well, particularly genes associated with BN and BED. Future candidate genes could also be discovered by studying hormones, metabolites, transcription factors, and protein profiles in specific phenotypes, such as people who have successfully recovered from eating disorders versus those who have not. If genes associated with AN can be correctly identified and the biological mechanisms deduced, there is the possibility that the findings could be used to not only help treatment people with AN, but also those who are obese. For example, if the genes that allow people with AN to avoid fixation with food despite low caloric intake can be identified and the biochemical pathway they act through be determined, pharmacotherapy options capitalizing on the information could be developed. The continued decrease in cost of next-generation methods of genome sequencing and the creation of consortiums providing access to genetic information for extremely large sample sizes will also play a significant role in determining the genetic architecture of eating disorders. The large sample sizes will provide adequate power for detecting the small effect sizes seen in polygenic forms of the diseases. However, for GWAS methods to be the most successful, eating disorder phenotypes need to be clearly defined and the same phenotypes used in multiple studies to allow for potential replication of findings. The moderate to high heritability of obesity and eating disorders in conjunction with the findings that the shared environment has little effect highlight the need for environmental changes to help people lead healthier lives. Obesity specifically is often viewed as the fault of the individual but understanding that weight is under genetic control and the way people are raised has little effect on their weight point to the need for stronger policies to help curb the obesogenic environment. Many people who are obese, as well as those who have BN and BED, struggle to moderate what and how much they are eating, showing a preference for unhealthy options. If these options were less readily available, or if health information was more accessible in conjunction with higher health literacy, people may be more equipped to make healthy choices. AN is a more complex disease, but if the desire to be thin is causing the voluntary restriction in food intake prompting the majority of cases of the disease in Western countries, there is a strong argument to invest more in changing the social environment to accept bodies of all shapes and sizes. For future research of both obesity and eating disorders, better defining phenotypes, taking advantage of large consortium data, and investigating novel hormones, metabolites, transcription factors, and protein profiles will be critical in better understanding the diseases. Novel phenotypes should also be investigated as the current missing heritability can be partially attributed to only looking at a limited range of phenotypes, such as just obese people rather than looking at people gaining and losing weight. 8.0 References ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY Abed R. The sexual competition hypothesis for eating disorders. Br J Med Psychol. 1998;71:525–47. Abizaid A, Gao Q, Horvath TL. Thoughts for food: brain mechanisms and peripheral energy balance. Neuron. 2006 Sep 21;51(6):691–702. Ahmad T, Lee I-M, Paré G, Chasman DI, Rose L, Ridker PM, et al. Lifestyle interaction with fat mass and obesity-associated (FTO) genotype and risk of obesity in apparently healthy U.S. women. Diabetes Care. 2011 Mar;34(3):675–80. Akkermann K, Kaasik K, Kiive E, Nordquist N, Oreland L, Harro J. The impact of adverse life events and the serotonin transporter gene promoter polymorphism on the development of eating disorder symptoms. J Psychiatr Res. Elsevier Ltd; 2012 Jan;46(1):38–43. Alegria M, Woo M, Cao Z, Torres M, Meng X, Striegel-moore R. Prevalence and correlates of eating disorders in Latinos in the United States. Int J Eat Disord. 2007;40:S15–S21. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, Virginia: American Psychiatric Association; 2013. Anand SS, Dagenais GR, Mohan V, Diaz R, Probstfield J, Freeman R, et al. Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study. Eur J Prev Cardiol. 2012 Aug;19(4):755–64. Ando T, Ishikawa T, Hotta M, Naruo T, Okabe K, Nakahara T, et al. No association of brain-derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese. Am J Med Genet. 2012 Jan;159B:48–52. Ando T, Komaki G, Naruo T, Okabe K, Takii M, Kawai K, et al. Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa. Am J Med Genet. 2006 Dec 5;141B:929–34. Asai M, Ramachandrappa S, Joachim M, Shen Y, Zhang R, Nuthalapati N, et al. Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science (80- ). 2013 Jul 19;341:275–8. Atalayer D, Gibson C, Konopacka A, Geliebter A. Ghrelin and eating disorders. Prog Neuro-Psychopharmacology Biol Psychiatry. Elsevier B.V.; 2013 Jan 10;40:70–82. Bachner-Melman R, Lerer E, Zohar AH, Kremer I, Elizur Y, Nemanov L, et al. Anorexia nervosa, perfectionism, and dopamine D4 receptor (DRD4). Am J Med Genet. 2007 Sep 5;144B:748–56. Baik J-H. Dopamine signaling in reward-related behaviors. Front Neural Circuits. 2013 Jan;7(152). Bailer UF, Frank GK, Henry SE, Price JC, Meltzer CC, Becker C, et al. Serotonin transporter binding after recovery from eating disorders. Psychopharmacology (Berl). 2007 Dec;195(3):315–24. Bariohay B, Roux J, Tardivel C, Trouslard J, Jean A, Lebrun B. Brain-derived neurotrophic factor/tropomyosin-related kinase receptor type B signaling is a downstream effector of the brainstem melanocortin system in food intake control. Endocrinology. 2009 Jun;150(6):2646–53. Barry D, Clarke M, Petry NM. Obesity and its relationship to addictions: is overeating a form of addictive behavior? Am J Addit. 2009;18(6):439–51. Barry DT, Grilo CM, Masheb RM. Gender differences in patients with binge eating disorder. Interrnational J Eat Disord. 2002;31:63–70. Bastard J-P, Feve B. The secretory face of the adipose cell: A trbiute to two queens, leptin and adiponectin. Biochimie. 2012;94(10):2063–190. Bauer F, Elbers CC, Adan RAH, Loos RJF, Onland-moret NC, Grobbee DE, et al. Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference 1 – 3. Am J Clin Nutr. 2009;90(3):951–9. Bello NT, Hajnal A. Dopamine and binge eating behaviors. Pharmacol Biochem Behav. 2011;97(1):25–33. Benzinou M, Creemers JWM, Choquet H, Lobbens S, Dina C, Durand E, et al. Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet. 2008 Aug;40(8):943–5. Bergen a W, van den Bree MBM, Yeager M, Welch R, Ganjei JK, Haque K, et al. Candidate genes for anorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa. Mol Psychiatry. 2003 Apr;8:397–406. Bergen AW, Yeager M, Welch R a, Haque K, Ganjei JK, van den Bree MBM, et al. Association of multiple DRD2 polymorphisms with anorexia nervosa. Neuropsychopharmacology. 2005 Sep;30:1703–10. Berkey CS, Rockett HRH, Field AE, Gillman MW, Frazier L, Camargo CA, et al. Activity , Dietary Intake , and Weight Changes in a Longitudinal Study of Preadolescent and Adolescent Boys and Girls Lindsay Frazier , Carlos A . Camargo , Jr , MD and Graham A . Colditz The online version of this article , along with updated information. Pediatrics. 2000;105(56). Boomsma D, Busjahn A, Peltonen L. Classical twin studies and beyond. Nat Rev Genet. 2002 Nov;3(11):872–82. Bradfield JP, Taal HR, Timpson NJ, Scherag A, Lecoeur C, Warrington NM, et al. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet. 2012 May;44(5):526–231. Brandys MK, Kas MJH, van Elburg A a, Ophoff R, Slof-Op’t Landt MCT, Middeldorp CM, et al. The Val66Met polymorphism of the BDNF gene in anorexia nervosa: new data and a meta-analysis. World J Biol Psychiatry. 2013 Aug;14:441–51. Brandys MK, Slof-Op’t Landt MCT, van Elburg A a, Ophoff R, Verduijn W, Meulenbelt I, et al. Anorexia nervosa and the Val158Met polymorphism of the COMT gene: meta-analysis and new data. Psychiatr Genet. 2012 Jun;22:130–6. Branson R, Potoczna N, Kral JG, Lentes K-U, Hoehe MR, Horber FF. Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. N Engl J Med. 2003 Mar 20;348(12):1096–103. Bray G a, Paeratakul S, Popkin BM. Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol Behav. 2004 Dec 30;83(4):549–55. Van den Bree MB, Eaves LJ, Dwyer JT. Genetic and environmental influences on eating patterns of twins aged >/=50 y. Am J Clin Nutr. 1999 Oct;70(4):456–65. Breen FM, Plomin R, Wardle J. Heritability of food preferences in young children. Physiol Behav. 2006 Jul 30;88(4-5):443–7. Brewerton TD, Lesem MD, Kennedy A, Garvey WT. Reduced plasma leptin concentrations in bulimia nervosa. Psychoneuroendocrinology. 2000 Oct;25:649–58. Brewerton TD, Lydiard RB, Laraia MT, Shook JE, Ballenger JC. CSF beta-endorphin and dynorphin in bulimia nervosa. Am J Psychiatry. 1992 Aug;149(8):1086–90. Brown KMO, Bujac SR, Mann ET, Campbell D a, Stubbins MJ, Blundell JE. Further evidence of association of OPRD1 & HTR1D polymorphisms with susceptibility to anorexia nervosa. Biol Psychiatry. 2007 Feb 1;61:367–73. Brownley KA, Berkman ND, Sedway JA, Lohr KN, Bulik CM. Binge eating disorder treatment: A systematic review of randomized controlled trials. Int J Eat Disord. 2007;40:337–48. Bruins-Slot L, Gorwood P, Bouvard M, Blot P, Adès J, Feingold J, et al. Lack of association between anorexia nervosa and D3 dopamine receptor gene. Biol Psychiatry. 1998 Jan 1;43:76–8. Brunkwall L, Ericson U, Hellstrand S, Gullberg B, Orho-melander M, Sonestedt E. Genetic variation in the fat mass and obesity-associated gene (FTO) in association with food preferences in healthy adults. Food Nutr Res. 2013;57:20028. Bulloch JM, Daly CJ. Autonomic nerves and perivascular fat: Interactive mechanisms. Pharmacol Ther. Elsevier Inc.; 2014 Feb 18;143:61–73. Bush WS, Moore JH. Chapter 11: Genome-wide association studies. PLoS Comput Biol. 2012 Jan;8(12):e1002822. Byrne NM, Wood RE, Schutz Y, Hills a P. Does metabolic compensation explain the majority of less-than-expected weight loss in obese adults during a short-term severe diet and exercise intervention? Int J Obes (Lond). Nature Publishing Group; 2012 Nov;36(11):1472–8. Cai G, Cole S a, Bastarrachea R a, Bastarrachea-Sosa R a, Maccluer JW, Blangero J, et al. Quantitative trait locus determining dietary macronutrient intakes is located on human chromosome 2p22. Am J Clin Nutr. 2004 Nov;80(5):1410–4. Calati R, De Ronchi D, Bellini M, Serretti A. The 5-HTTLPR polymorphism and eating disorders: a meta-analysis. Int J Eat Disord. 2011 Apr;44(3):191–9. Calle EE, Rodriquez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. New Engl J Med. 2003;348(17):1625–38. Callier S, Husain R, Simpson R. Genomic data-sharing: what will be our legacy? Front Genet. 2014 Jan;5:34. Do Carmo JM, Silva AA, Dubinion J, Sessums PO, Sabira H, Wang Z, et al. Control of metabolic and cardiovascular function by the leptin-brain melanocortin pathway. IUBMB Life. 2013;65(8):201–7. Carnell S, Haworth CM a, Plomin R, Wardle J. Genetic influence on appetite in children. Int J Eat Disord. 2008 Oct;32(10):1468–73. Carter JC, Fairburn CG. Cognitive-behavioral self-help for binge eating disorder: A controlled effectiveness study. J Counsulting Clin Psychol. 1998;66(4):616–23. Cassin SE, von Ranson KM. Personality and eating disorders: a decade in review. Clin Psychol Rev. 2005 Nov;25(7):895–916. Castellini G, Ricca V, Lelli L, Bagnoli S, Lucenteforte E, Faravelli C, et al. Association between serotonin transporter gene polymorphism and eating disorders outcome: a 6-year follow-up study. Am J Med Genet. 2012 Jul;159B:491–500. De Castro JM. Genetic influences on daily intake and meal patterns of humans. Physiol Behav. 1993 Apr;53(4):7777–82. De Castro JM, Lilenfeld LRR. Influence of heredity on dietary restraint, disinhibition, and perceived hunger in humans. Nutr. 2005 Apr;21(4):446–55. Cecil J, Dalton M, Finlayson G, Blundell J, Hetherington M, Palmer C. Obesity and eating behaviour in children and adolescents: contribution of common gene polymorphisms. Int Rev Psychiatry. 2012 Jun;24(3):200–10. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CNA. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med. 2008;359:2558–66. Cellini E, Nacmias B, Brecelj-anderluh M, Bellodi L, Boni C, Di D, et al. Case – control and combined family trios analysis of three polymorphisms in the ghrelin gene in European patients with anorexia and bulimia nervosa. Psychiatr Genet. 2006;700:51–2. Chan LF, Webb TR, Chung T-T, Meimaridou E, Cooray SN, Guasti L, et al. MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6146–51. Choquet H, Meyre D. Genomic insights into early-onset obesity. Genome Med. 2010 Jan;2(36). Choquet H, Meyre D. Genetics of obesity: What have we Learned? Curr Genomics. 2011 a May;12(3):169–79. Choquet H, Meyre D. Molecular basis of obesity: current status and future prospects. Curr Genomics. 2011 b May;12(3):154–68. Chu AY, Workalemahu T, Paynter NP, Rose LM, Giulianini F, Tanaka T, et al. Novel locus including FGF21 is associated with dietary macronutrient intake. Hum Mol Genet. 2013 May 1;22(9):1895–902. Chung WK. An overview of monogenic and syndromic obesities in humans. Pediatr Blood Cancer. 2012;58(1):122–8. Cole SA, Butte NF, Voruganti VS, Cai G, Haack K, Jr JWK, et al. Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic. 2010;22. Cooke LJ, Haworth CM, Wardle J. Genetic and environmental influences on children’s food neophobia. Am J Clin Nutr. 2007;86:428–33. Corander MP, Coll AP. Melanocortins and body weight regulation: Glucocorticoids, agouti-related protein and beyond. Eur J Pharmacol. 2011;1(11):111–8. Corella D, Arnett DK, Tucker KL, Kabagambe EK, Tsai M, Parnell LD, et al. A high intake of saturated fatty acids strengthens the association between the fatt mass and and obesity-associated gene and BMI. J Nutr. 2011;141:2219–25. Cornelis MC, Rimm EB, Curhan GC, Kraft P, Hunter DJ, Hu FB, et al. Obesity susceptibility loci and uncontrolled eating, emotional eating and cognitive restraint behaviors in men and women. Obesity. 2014 May;22(5):135–41. Creemers JWM, Choquet H, Stijnen P, Vatin V, Pigeyre M, Beckers S, et al. Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity. Diabetes. 2012 Feb;61(2):383–90. Currin L, Schmidt U, Treasure J, Jick H. Time trends in eating disorder incidence. Br J Psychiatry. 2005 Feb;186:132–5. Dardennes RM, Zizzari P, Tolle V, Foulon C, Kipman A, Romo L, et al. Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and age of onset. Psychoneuroendocrinology. 2007 Feb;32(2):106–13. Davis C, Levitan RD, Yilmaz Z, Kaplan AS, Carter JC, Kennedy JL. Binge eating disorder and the dopamine D2 receptor: genotypes and sub-phenotypes. Prog Neuro-Psychopharmacology Biol Psychiatry. Elsevier Inc.; 2012 Aug 7;38(2):328–35. Dina C, Meyre D, Gallina S, Durand E, K?rner A, Jacobson P, et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007 Jun;39(6):724–6. Dmitrzak-Weglarz M, Moczko J, Skibinska M, Slopien A, Tyszkiewicz M, Pawlak J, et al. The study of candidate genes related to the neurodevelopmental hypothesis of anorexia nervosa: classical association study versus decision tree. Psychiatry Res. Elsevier; 2013 Mar 30;206(1):117–21. Doche ME, Bochukova EG, Su H, Pearce LR, Keogh JM, Henning E, et al. Human SH2B1 mutations are associated with maladaptive behaviors and obesity. J Clin Invest. 2012;122(12):4732–6. Dolezalova R, Lacinova Z, Dolinkova M, Kleiblova P, Haluzikova D, Housa D, et al. Changes of endocrine function of adipose tissue in anorexia nervosa: comparison of circulating levels versus subcutaneous mRNA expression. Clin Endocrinol (Oxf). 2007 Nov;67(5):674–8. Dougkas A, Yaqoob P, Givens DI, Reynolds CK, Minihane AM. The impact of obesity-related SNP on appetite and energy intake. Brit J Nutr. 2013 Sep 28;110(6):1151–6. Dubois L, Diasparra M, Bédard B, Kaprio J, Fontaine-Bisson B, Pérusse D, et al. Gene-environment contributions to energy and macronutrient intakes in 9-year-old children: results from the Quebec Newborn Twin Study. Physiol Behav. Elsevier Inc.; 2013 Jul 2;119:30–7. Dudbridge F, Gusnanto A. Estimation of significance thresholds for genomewide association scans. Genet Epidemiol. 2008 Apr;32(3):227–34. Eddy KT, Dorer DJ, Franko DL, Tahilani K, Thompson-Brenner H, Herzog DB. Diagnostic crossover in Anorexia Nervosa and Bulimia Nerovsa: implications for the DSM-V. Am J Psychiatry. 2013;165:245–50. Elks CE, den Hoed M, Zhao JH, Sharp SJ, Wareham NJ, Loos RJF, et al. Variability in the heritability of body mass index: a systematic review and meta-regression. Front Endocrinol (Lausanne). 2012 Jan;3:29. Fairburn CG, Cooper Z, Doll H a, Norman P, O’Connor M. The natural course of bulimia nervosa and binge eating disorder in young women. Arch Gen Psychiatry. 2000 Jul;57(7):659–65. Fairburn CG, Harrison PJ. Eating disorders. Lancet. 2003 Feb 1;361(9355):407–16. Faith MS, Heo M, Keller KL, Pietrobelli A. Child food neophobia is heritable, associated with less compliant eating, and moderates familial resemblance for BMI. Obesity. 2013 Aug;21(8):1650–5. Faith MS, Keller KL, Johnson SL, Pietrobelli A, Matz PE, Must S, et al. Familial aggregation of energy intake in children. Am J Clin Nutr. 2004 May;79(5):844–50. Faith MS, Rhea SA, Corley RP, Hewitt JK. Genetic and shared environmental influences on children’s 24-h food and beverage intake: sex differences at age 7 y. Am J Clin Nutr. 2008;87:903–11. Farooqi IS, Volders K, Stanhope R, Heuschkel R, White A, Lank E, et al. Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab. 2007 Sep;92(9):3369–73. Favaro A, Ferrara S, Santonastaso P. The spectrum of eating disorders in young women: A prevalence study in a general population sample. Psychosom Med. 2003 Jul 1;65(4):701–8. Field AE, Sonneville KR, Micali N, Crosby RD, Swanson S a, Laird NM, et al. Prospective association of common eating disorders and adverse outcomes. Pediatrics. 2012 Aug;130(2):e289–295. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet. Elsevier Ltd; 2011 Feb 12;377(9765):557–67. Fisher JO, Cai G, Jaramillo SJ, Cole S a, Comuzzie AG, Butte NF. Heritability of hyperphagic eating behavior and appetite-related hormones among Hispanic children. Obesity. 2007 Jun;15(6):1484–95. Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. J Am Med Assoc. 2003;289(2):187–93. Fornari VM, Braun DL, Sunday SR, Sandberg DE, Matthews M, Chen I, et al. Seasonal patterns in eating disorder subgroups. Compr Psychiatry. 1994;35(6):450–6. Foulkes WD, Shuen AY. In brief: BRCA1 and BRCA2. J Pathol. 2013 Aug;230(4):347–9. Fox EA, Byerly MS. Physiological Regulation of Appetite A mechanism underlying mature-onset obesity?: evidence from the hyperphagic phenotype of brain-derived neurotrophic factor mutants. 2004;47907:994–1004. Frank GR, Fox J, Candela N, Jovanovic Z, Bochukova E, Levine J, et al. Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency. Mol Genet Metab. The Authors; 2013;110(1-2):191–4. Franko DL, Keshaviah A, Eddy KT, Krishna M, Davis MC, Keel PK, et al. A longitudinal investigation of mortality in anorexia nervosa and bulimia nervosa. Am J Psychiatry. 2013 Aug 1;170(8):917–25. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science (80- ). 2007 May 11;316:889–94. French SA, H EL, JEffery RW, Blundell JE, Wardle J. Eating behavior dimensions. Associations with energy intake and body weight. A review. Appetite. 2012;59(1):541–9. Gaesser GA. Carbohydrate quantity and quality in relation to body mass index. J Am Diet Assoc. 2007 Oct;107(10):1768–80. Gamero-Villarroel C, Gordillo I, Carrillo JA, García-Herráiz A, Flores I, Jiménez M, et al. BDNF genetic variability modulates psychopathological symptoms in patients with eating disorders. Eur Child Adolesc Psychiatry. 2013 Nov 29; Gatward N. Anorexia nervosa: an evolutionary puzzle. Eur Eat Disord Rev. 2007 Jan;15(1):1–12. Gauderman J, Morrison J. QUANTO. Los Angeles, California: Department of Preventive Medicine, University of Southern California; 2001. Geller F, Reichwald K, Dempfle A, Illig T, Vollmert C, Herpertz S, et al. Melanocortin-4 receptor gene variant I103 is negatively associated with obesity. Am J Hum Genet. 2004 Mar;74(3):572–81. Gervasini G, Gordillo I, García-Herráiz A, Flores I, Jiménez M, Monge M, et al. Influence of dopamine polymorphisms on the risk for anorexia nervosa and associated psychopathological features. J Clin Psychopharmacol. 2013 Aug;33(4):551–5. Ghaderi A, Scott B. Prevalence, incidence and prospective risk factors for eating disorders. Acta Psychiatr Scand. 2001 Aug;104(2):122–30. Gluck ME, Geliebter A. Racial/ethnic differences in body image and eating behaviors. Eat Behav. 2002 Jan;3(2):143–51. Golan D, Rosset S. Accurate estimation of heritability in genome wide studies using random effects models. Bioinformatics. 2011 Jul 1;27(13):i317–23. Gortmaker SL, Swinburn BA, Levy D, Carter R, Mabry PL, Finegood DT, et al. Changing the future of obesity: science, policy, and action. Lancet. Elsevier Ltd; 2011 Aug 27;378(9793):838–47. Gorwood P. The human genetics of anorexia nervosa. Eur J Pharmacol. 2003 Nov 7;480:163–70. Gorwood P. Eating disorders, serotonin transporter polymorphisms and potential treatment response. Am J Pharmacogenomics. 2004;4:9–17. Gratacòs M, González JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry. 2007 Apr 1;61(7):911–22. Gray J, Yeo GSH, Cox JJ, Morton J, Adlam A-LR, Keogh JM, et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes. 2006 Dec;55(12):3366–71. Gray J, Yeo GSH, Cox JJ, Morton J, Adlam AR, Keogh M, et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes. 2008;55(12):3366–71. Gray LJ, Cooper N, Dunkley a, Warren FC, Ara R, Abrams K, et al. A systematic review and mixed treatment comparison of pharmacological interventions for the treatment of obesity. Obes Rev. 2012 Jun;13(6):483–98. Grice DE, Halmi K a, Fichter MM, Strober M, Woodside DB, Treasure JT, et al. Evidence for a susceptibility gene for anorexia nervosa on chromosome 1. Am J Hum Genet. 2002 Mar;70(3):787–92. Grilo CM, Masheb RM. Onset of dieting vs binge eating in outpatients with binge eating disorder. Int J Obes. 2000 Apr;24(4):404–9. Grucza RA, Przybeck TR, Cloninger CR. Prevalence and correlates of binge eating disorder in a community sample. Compr Psychiatry. 2007;48(2):124–31. Guisinger S. Adapted to flee famine: adding an evolutionary perspective on anorexia nervosa. Psychol Rev. 2003 Oct;110(4):745–61. Gulati P, Yeo GSH. The biology of FTO: from nucleic acid demethylase to amino acid sensor. Diabetologia. 2013 Oct;56(10):2113–21. Haleem DJ. Serotonin neurotransmission in anorexia nervosa. Behav Pharmacol. 2012 Sep;23:478–95. Hales CN, Barker DJP. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Int J Epidemiol. 2013 Oct;42(5):1215–22. Halkjaer J, Tjonneland A, Thomsen BL, Overvad K, Sorensen TI. Intake of macronutrients as predictors of 5-y changes in waist. Am J Clin Nutr. 2006;84(9):789–97. Han JC, Liu Q-R, Jones M, Levinn RL, Menzie CM, Jefferson-George KS, et al. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med. 2008 Aug 28;359(9):918–27. Harten PN Van, Hermans KME, Katzman MA, Matroos GE, Susser ES. The Incidence of Anorexia Nervosa on Cura?ao. Am J Psychiatry. 2005;162:748–52. Hartmann AS, Greenberg JL, Wilhelm S. The relationship between anorexia nervosa and body dysmorphic disorder. Clin Psychol Rev. 2013;33(5):675–85. Hasselbalch AL, Heitmann BL, Kyvik KO, S?rensen TIA. Studies of twins indicate that genetics influence dietary intake. J Nutr. 2008;138:2406–12. Haupt A, Thamer C, Staiger H, Tschritter O, Kirchhoff K, Machicao F, et al. Variation in the FTO gene influences food intake but not energy expenditure. Exp Clin Endocrinol Diabetes. 2009 Apr;117(4):194–7. Hausenblas H a, Campbell A, Menzel JE, Doughty J, Levine M, Thompson JK. Media effects of experimental presentation of the ideal physique on eating disorder symptoms: a meta-analysis of laboratory studies. Clin Psychol Rev. Elsevier Ltd; 2013 Feb;33(1):168–81. Hay P. The epidemiology of eating disorder behaviors: an Australian community-based survey. Int J Eat Disord. 1998 May;23(4):371–82. Hay PJ, Mond J, Buttner P, Darby A. Eating disorder behaviors are increasing: findings from two sequential community surveys in South Australia. PLoS One. 2008 Jan;3(2):e1541. Heaner MK, Walsh BT. A history of the identification of the characteristics eating disturbances of bulimia nervosa, binge eating disorders and anorexia nervosa. Appetite. Elsevier Ltd; 2013 Jun;65:185–8. Hebebrand J, Geller F, Dempfle A, Heinzel-Gutenbrunner M, Raab M, Gerber G, et al. Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations. Mol Psychiatry. 2004 Aug;9(8):796–800. Hinney A, Bornscheuer A, Depenbusch M, Mierke B, T?lle A, Middeke K, et al. No evidence for involvement of the leptin gene in anorexia nervosa, bulimia nervosa, underweight or early onset extreme obesity: identification of two novel mutations in the coding sequence and a novel polymorphism in the leptin gene linked upstream regio. Mol Psychiatry. 1998 Nov;3(6):539–43. Hinney A, Nguyen TT, Scherag A, Friedel S, Br?nner G, Müller TD, et al. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS One. 2007 Jan;2(12):e1361. Hinney A, Schneider J, Ziegler A, Lehmkuhl G, Poustka F, Schmidt MH, et al. No evidence for involvement of polymorphisms of the dopamine D4 receptor gene in anorexia nervosa, underweight, and obesity. Am J Med Genet. 1999 Dec 15;88(6):594–7. Ho N, Sommers M. Anhedonia: a concept analysis. Arch Psychiatr Nurs. Elsevier Inc.; 2013 Jun;27(3):121–239. Hoed M Den, Westerterp-Plantenga MS, Bouwman FG, Mariman ECM, Westerterp KR. Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO. Am J Clin Nutr. 2009;90:1426–32. Hoek HW. Incidence, prevalence and mortality of anorexia nervosa and other eating disorders. Curr Opin Psychiatry. 2006 Jul;19(4):389–94. Hoek HW, van Hoeken D. Review of the prevalence and incidence of eating disorders. Int J Eat Disord. 2003 Dec;34(4):383–96. Holtom-Viesel A, Allan S. A systematic review of the literature on family functioning across all eating disorder diagnoses in comparison to control families. Clin Psychol Rev. Elsevier Ltd; 2014 Feb;34(1):29–43. Hong KW, Oh B. Recapitulation of genome-wide association studies on body mass index in the Korean population. Int J Obes. 2012 Aug;36(8):1127–30. Horstmann A, Kovacs P, Kabisch S, Boettcher Y, Schloegl H, T?njes A, et al. Common genetic variation near MC4R has a sex-specific impact on human brain structure and eating behavior. PLoS One. 2013 Jan;8(9):e74362. Hotta M, Ohwada R, Akamizu T, Shibasaki T, Takano K, Kangawa K. Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: a pilot study. Endocr J. 2009 Jan;56(9):1119–28. Hu X, Karwautz A, Wagner G, Holliday J, Li T, Treasure J, et al. No association between a promoter polymorphism in the noradrenaline transporter gene and anorexia nervosa. Psychiatr Genet. 2007 Aug;17(4):247–8. Hudson JI, Hiripi E, Jr HGP, Kessler RC. The prevalence and correlates of eating disorders in the National Comorbidity Survey replication. Biol Psychiatry. 2008;61(3):348–58. Hur YM, Bouchard TJ, Eckert E. Genetic and environmental influences on self-reported diet: a reared-apart twin study. Physiol Behav. 1998 Jul;64(5):629–36. IBM Corp. IBM SPSS Statistics for Windows. Armonk, NY: IBM Corp; 2011. Ioannidis JP a, Boffetta P, Little J, O’Brien TR, Uitterlinden AG, Vineis P, et al. Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol. 2008 Feb;37(1):120–32. Jaite C, Hoffmann F, Glaeske G, Bachmann CJ. Prevalence, comorbidities and outpatient treatment of anorexia and bulimia nervosa in German children and adolescents. Eat Weight Disord. 2013 Apr 16;18(2):157–65. Janssens CJW, 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 Aug;9(8):528–35. Johnson RD. Opioid involvement in feeding behaviour and the pathogenesis of certain eating disorders. Med Hypotheses. 1995 Nov;45(5):491–7. J?rgensen L, S?rensen T, Schroll M, Larsen S. Influence of dietary factors on weight change assessed by multivariate graphical models. Int J Obes Relat Metab Disord. 1995;19(12):909–15. Joyner MJ, Prendergast FG. Chasing Mendel: five questions for personalized medicine. J Physiol. 2014 Jun 1;592(11):2381–8. Jung CH, Kim M-S. Molecular mechanisms of central leptin resistance in obesity. Arch Pharm Res. 2013 Feb;36(2):201–7. Kardum I, Gra A, Hudek-Kne?evi J. Evolutionary explanations of eating disorders. Psychol Top. 2008;17(2):247–63. Karwautz A, Rabe-Hesketh S, Hu X, Zhao J, Sham P, Collier D a, et al. Individual-specific risk factors for anorexia nervosa: a pilot study using a discordant sister-pair design. Psychol Med. 2001 Feb;31(2):317–29. Kaye W. Neurobiology of anorexia and bulimia nervosa. Physiol Behav. 2008 Apr 22;94(1):121–35. Kaye WH, Klump KL, Frank GK, Strober M. Anorexia and bulimia nervosa. Annu Rev Med. 2000 Jan;51:299–313. Kaye WH, Wierenga CE, Bailer UF, Simmons AN, Bischoff-Grethe A. Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends Neurosci. Elsevier Ltd; 2013 Feb;36(2):110–20. Keating BJ, Tischfield S, Murray SS, Bhangale T, Price TS, Glessner JT, et al. Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. PLoS One. 2008 Jan;3(10):e3583. Keating C. Theoretical perspective on anorexia nervosa: the conflict of reward. Neurosci Biobehav Rev. 2010 Jan;34(1):73–9. Keating C, Tilbrook AJ, Rossell SL, Enticott PG, Fitzgerald PB. Reward processing in anorexia nervosa. Neuropsychologia. Elsevier Ltd; 2012 Apr;50(5):567–75. Keel PK, Brown T a. Update on course and outcome in eating disorders. Int J Eat Disord. 2010 Apr;43(3):195–204. Keel PK, Heatherton TF, Dorer DJ, Joiner TE, Zalta AK. Point prevalence of bulimia nervosa in 1982, 1992, and 2002. Psychol Med. 2006 Jan;36(1):119–27. Keel PK, Klump KL. Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology. Psychol Bull. 2003 Sep;129(5):747–69. Kelemen LE, Anand SS, Vuksan V, Yi Q, Teo KK, Devanesen S, et al. Development and evaluation of cultural food frequency questionnaires for South Asians, Chinese, and Europeans in North America. J Am Diet Assoc. 2003 Sep;103(9):1178–84. Keski-Rahkonen A, Hoek HW, Linna MS, Raevuori A, Sihvola E, Bulik CM, et al. Incidence and outcomes of bulimia nervosa: a nationwide population-based study. Psychol Med. 2009 May;39(5):823–31. Keski-Rahkonen A, Raevuori A, Bulik CM, Hoek HW, Sihvola E, Kaprio J, et al. Depression and drive for thinness are associated with persistent bulimia nervosa in the community. Eur Eat Disord Rev. 2013 Mar;21(2):121–9. Keskitalo K, Silventoinen K, Tuorila H, Perola M, Pietil?inen KH, Rissanen A, et al. Genetic and environmental contributions to food use patterns of young adult twins. Physiol Behav. 2008 a Jan 28;93:235–42. Keskitalo K, Tuorila H, Spector TD, Cherkas LF, Knaapila A, Kaprio J, et al. The Three-Factor Eating Questionnaire, body mass index, and responses to sweet and salty fatty foods: a twin study of genetic and environmental associations. Am J Clin Nutr. 2008 b Aug;88:263–71. Kessler RC, Berglund P a, Chiu WT, Deitz AC, Hudson JI, Shahly V, et al. The prevalence and correlates of binge eating disorder in the World Health Organization World Mental Health Surveys. Biol Psychiatry. 2013 May 1;73(9):904–14. Kindler J, Bailer U, de Zwaan M, Fuchs K, Leisch F, Grün B, et al. No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders. Nord J Psychiatry. 2011 Jun;65(3):203–7. Kinzl JF, Traweger C, Trefalt E, Mangweth B, Biebl W. Binge eating disorder in females: a population-based investigation. Int J Eat Disord. 1999 Apr;25(3):287–92. Klein DA, Walsh BT. Eating disorders. Int Rev Psychiatry. 2003 Aug;15(3):205–16. Klump KL, Kaye WH, Strober M. The evolving genetic foundations of eating disorders. Psychiatr Clin North Am. 2001 Jun;24(2):215–25. Klump KL, Wonderlich S, Lehoux P, Lilenfeld LRR, Bulik CM. Does environment matter? A review of nonshared environment and eating disorders. Int J Eat Disord. 2002 Mar;31(2):118–35. Knaapila A, Silventoinen K, Broms U, Rose RJ, Perola M, Kaprio J, et al. Food neophobia in young adults: genetic architecture and relation to personality, pleasantness and use frequency of foods, and body mass index--a twin study. Behav Genet. 2011 Jul;41:512–21. Knaapila A, Tuorila H, Silventoinen K, Keskitalo K, Kallela M, Wessman M, et al. Food neophobia shows heritable variation in humans. Physiol Behav. 2007 Aug 15;91:573–8. Kontis D, Theochari E. Dopamine in anorexia nervosa: a systematic review. Behav Pharmacol. 2012 Sep;23:496–515. Kral JG, N?slund E. Surgical treatment of obesity. Nat Clin Pract Endocrinol Metab. 2007 Aug;3(8):574–83. Lear S a, Deng WQ, Paré G, Sulistyoningrum DC, Loos RJF, Devlin A. Associations of the FTO rs9939609 variant with discrete body fat depots and dietary intake in a multi-ethnic cohort. Genet Rest Camb. 2011 Dec;93(6):419–26. Lee H-J, Kim IK, Kang JH, Ahn Y, Han B-G, Lee J-Y, et al. Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans. Clin Chim Acta. Elsevier B.V.; 2010 Nov 11;411:1716–22. Lehnert T, Sonntag D, Konnopka A, Riedel-Heller S, K?nig H-H. Economic costs of overweight and obesity. Best Pract Res Clin Endocrinol Metab. 2013 Apr;27(2):105–15. Levitan RD, Wendland B. Novel “thrifty” models of increased eating behaviour. Curr Psychiatry Rep. 2013 Nov;15(11):408. 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. 2014; Llewellyn CH, Jaarsveld CHM Van, Boniface D, Carnell S, Wardle J. Eating rate is a heritable phenotype related to weight in children. Am J Clin Nutr. 2008;88:1560–6. Llewellyn CH, Jaarsveld CHM Van, Johnson L, Carnell S, Wardle J. Nature and nurture in infant appetite?: analysis of the Gemini twin birth cohort. Am J Clin Nutr. 2010;91:1172–9. Llewellyn CH, Jaarsveld CHM Van, Plomin R, Fisher A, Wardle J. Inherited behavioral susceptibility to adiposity in infancy?: a multivariate genetic analysis of appetite and weight in the Gemini birth cohort 1 – 3. 2012; Llewellyn CH, Trzaskowski M, van Jaarsveld CHM, Plomin R, Wardle J. Satiety mechanisms in genetic risk of obesity. JAMA Pediatr. 2014 May;168(4):338–44. Lloyd DJ, Bohan S, Gekakis N. Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice. Hum Mol Genet. 2006 Jun 1;15(11):1884–93. Lofrano-Prado MC, Prado WL Do, de Piano A, Tock L, Caranti DA, Nascimento CMO Do, et al. Eating disorders in adolescents: correlations between symptoms and central control of eating behavior. Eat Behav. 2011 Jan;12(1):78–82. Lubrano-Berthelier C, Dubern B, Lacorte J-M, Picard F, Shapiro A, Zhang S, et al. Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating. J Clin Endocrinol Metab. 2006 May;91(5):1811–8. Lyons WE, Mamounas L a, Ricaurte G a, Coppola V, Reid SW, Bora SH, et al. Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15239–44. Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997 Jul;27(4):325–51. Maj M, Monteleone P. Genetic susceptibility to eating disorders: associated polymorphisms and pharmacogenetic suggestions. Pharmacogenomics. 2008;9(10):1487. Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat Rev Endocrinol. 2013;9:13–27. Manolio T a, Collins FS, Cox NJ, Goldstein DB, Hindorff L a, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. Nature Publishing Group; 2009 Oct 8;461(7265):747–53. Marian AJ. Elements of “missing heritability.”Curr Opin Cardiol. 2012 May;27:197–201. Marques L, Alegria M, Becker A, Chen C, Fang A, Chosak A, et al. Comparative prevalence, correlates of impairment, and service utilization for eating disorders across U.S. ethnic groups: Implications for reducing ethnic disparities in health care access for eating disorders. Int J Eat Disord. 2011;44(5):412–20. Martaskova D, Slachtova L, Kemlink D, Zahorakova D, Papezova H. Polymorphisms in serotonin-related genes in anorexia nervosa. The first study in Czech population and meta-analyses with previously performed studies. Folia Biolgica. 2009;55:192–7. Mathes WF, Brownley, Kimberly A, Mo X, Bulik CM. The biology of binge eating. Appetite. 2010;52(3):545–53. McAllister EJ, Dhurandhar N V, Keith SW, Aronne LJ, Barger J, Baskin M, et al. Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr. 2009 Nov;49(10):868–913. Mccaffery JM, Papandonatos GD, Peter I, Huggins GS, Raynor HA, Delahanty LM, et al. Obesity susceptibility loci and dietary intake in the Look AHEAD Trial. Am J Clin Nutr. 2012;95:1477–86. Meczekalski B, Podfigurna-Stopa A, Katulski K. Long-term consequences of anorexia nervosa. Maturitas. Elsevier Ireland Ltd; 2013 Jul;75(3):215–20. Mencarelli M, Dubern B, Alili R, Maestrini S, Benajiba L, Tagliaferri M, et al. Rare melanocortin-3 receptor mutations with in vitro functional consequences are associated with human obesity. Hum Mol Genet. 2011 Jan 15;20(2):392–9. Mercader JM, Ribasés M, Gratacòs M, González JR, Bayés M, de Cid R, et al. Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia. Genes, Brain Behav. 2007 Nov;6(8):706–16. Merle J V, Haas V, Burghardt R, D?hler N, Schneider N, Lehmkuhl U, et al. Agouti-related protein in patients with acute and weight-restored anorexia nervosa. Psychol Med. 2011 Oct;41(10):2183–92. Mitchell BD, Rainwater DL, Hsueh W-C, Kennedy AJ, Stern MP, Maccluer JW. Familial aggregation of nutrient intake and physical activity: results from the San Antonio Family Heart Study. Ann Epidemiol. 2003 Feb;13(2):128–35. Mitchell NS, Catenacci V a, Wyatt HR, Hill JO. Obesity: overview of an epidemic. Psychiatr Clin North Am. Elsevier Inc.; 2011 Dec;34(4):717–32. Mitchison D, Hay PJ. The epidemiology of eating disorders: genetic, environmental, and societal factors. Clin Epidemiol. 2014 Jan;6:89–97. Moleres A, Ochoa MC, Rendo-Urteaga T, Martínez-González MA, Azcona San Julián MC, Martínez JA, et al. Dietary fatty acid distribution modifies obesity risk linked to the rs9939609 polymorphism of the fat mass and obesity-associated gene in a Spanish case-control study of children. Brit J Nutr. 2012 Feb;107(4):533–8. Monteleone P, DiLieto A, Castaldo E, Maj M. Leptin functioning in eating disorders. CNS Spectr. 2004;9(7):523–9. Monteleone P, Tortorella A, Castaldo E, Di Filippo C, Maj M. No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene with anorexia nervosa or bulimia nervosa. Neurosci Lett. 2006 May 8;398(3):325–7. Moriya J, Takimoto Y, Yoshiuchi K, Shimosawa T, Akabayashi A. Plasma agouti-related protein levels in women with anorexia nervosa. Psychoneuroendocrinology. 2006 Oct;31(9):1057–61. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. J Am Med Assoc. 1999;282(16):1523–9. Nakazato M, Hashimoto K, Shimizu E, Niitsu T, Iyo M. Possible involvement of brain-derived neurotrophic factor in eating disorders. Life. 2012 May;64(5):355–61. Neel J V. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress.”Am J Hum Genet. 1962;14:353–62. Neel J V. The thrifty genotype in 1998. Nutr Rev. 1999;57:S2–S7. Nelson SM, Telfer EE, Anderson R a. The ageing ovary and uterus: new biological insights. Hum Reprod Update. 2013;19(1):67–83. Nicdao EG, Hong S, Takeuchi DT. Prevalence and correlates of eating disorders among Asian Americans: Results from the National Latino and Asian American Study. Int J Eat Disord. 2007;40:S22–S26. O’Rahilly S, Farooqi IS. Human obesity as a heritable disorder of the central control of energy balance. Int J Obes (Lond). 2008 Dec;32 Suppl 7:S55–61. O’Shaughnessy R, Dallos R. Attachment research and eating disorders: a review of the literature. Clin Child Psychol Psychiatry. 2009 Oct;14(4):559–74. Park SL, Cheng I, Pendergrass S a, Kucharska-Newton AM, Lim U, Ambite JL, et al. Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations: the PAGE study. Am J Epidemiol. 2013 Sep 1;178(5):780–90. Phillips CM, Kesse-Guyot E, Mcmanus R, Hercberg S, Lairon D, Planells R, et al. High dietary saturated fat intake accentuates obesity risk associated with the fatt mas and obesity-associated gene in adults. J Nutr. 2012;142:824–31. Pike KM, Dohm F a, Striegel-Moore RH, Wilfley DE, Fairburn CG. A comparison of black and white women with binge eating disorder. Am J Psychiatry. 2001 Sep;158(9):1455–60. Polsinelli GN, Levitan RN, De Luca V. 5-HTTLPR polymorphism in bulimia nervosa: a multiple-model meta-analysis. Psychiatr Genet. 2012 Oct;22(5):219–25. Prentice A, Jebb S. Energy Intake / Physical Activity Interactions in the Homeostasis of Body Weight Regulation. 2004;62(7). Prentice AM, Hennig BJ, Fulford AJ. Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release? Int J Obes. 2008 Nov;32(11):1607–10. Preti A, Girolamo G De, Vilagut G, Alonso J, Graaf R De, Bruffaerts R, et al. The epidemiology of eating disorders in six European countries: results of the ESEMeD-WMH project. J Psychiatr Res. Elsevier Ltd; 2009 Sep;43(14):1125–32. Quinton ND, Meechan DW, Brown K, Eastwood H, Blakemore a IF. Single nucleotide polymorphisms in the leptin receptor gene: studies in anorexia nervosa. Psychiatr Genet. 2004 Dec;14(4):191–4. Rask-Andersen M, Olszewski PK, Levine AS, Schi?th HB. Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake. Brain Res Rev. Elsevier B.V.; 2010 Mar;62(2):147–64. Razak F, Anand SS, Shannon H, Vuksan V, Davis B, Jacobs R, et al. Defining obesity cut points in a multiethnic population. Circulation. 2007 Apr 24;115:2111–8. Reichborn-Kjennerud T, Bulik CM, Sullivan PF, Tambs K, Harris JR. Psychiatric and medical symptoms in binge eating in the absence of compensatory behaviors. Obes Res. 2004 Sep;12(9):1445–54. Ribasés M, Gratacòs M, Armengol L, de Cid R, Badía A, Jiménez L, et al. Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type. Mol Psychiatry. 2003 Aug;8(8):745–51. Ribasés M, Gratacòs M, Fernández-Aranda F, Bellodi L, Boni C, Anderluh M, et al. Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations. Eur J Hum Genet. 2005 Apr;13(4):428–34. Rijsdijk F V, Sham PC. Analytic approaches to twin data using structural equation models. Brief Bioinform. 2002 Jun;3(2):119–33. Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R, et al. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol. 2001 Oct;15(10):1748–57. Robiou-du-Pont S, Yengo L, Vaillant E, Lobbens S, Durand E, Horber F, et al. Common variants near BDNF and SH2B1 show nominal evidence of association with snacking behavior in European populations. J Mol Med. 2013 May 3; Rothstein M a. Should researchers disclose results to descendants? Am J Bioeth. 2013 Jan;13(10):64–5. Rukh G, Sonestedt E, Melander O, Hedblad B, Wirf?lt E, Ericson U, et al. Genetic susceptibility to obesity and diet intakes: association and interaction analyses in the Malm? Diet and Cancer Study. Genes Nutr. 2013 Jul 17;8(6):535–47. Runkel N, Colombo-Benkmann M, Hüttl TP, Tigges H, Mann O, Sauerland S. Bariatric surgery. Dtsch Arztebl Int. 2011 May;108(20):341–6. Rutters F, Lemmens SGT, Born JM, Bouwman F, Nieuwenhuizen AG, Mariman E, et al. Genetic associations with acute stress-related changes in eating in the absence of hunger. Patient Educ Couns. Elsevier Ireland Ltd; 2010 Jun;79(3):367–71. Schelbert KB. Comorbidities of obesity. Prim Care Clin Off Pr. Elsevier Ltd; 2009 Jun;36(2):271–85. Scherag S, Hebebrand J, Hinney A. Eating disorders: the current status of molecular genetic research. Eur Child Adolesc Psychiatry. 2010 Mar;19(3):211–6. Scheurink AJW, Boersma GJ, Nerg?rdh R, S?dersten P. Neurobiology of hyperactivity and reward: agreeable restlessness in anorexia nervosa. Physiol Behav. Elsevier Inc.; 2010 Jul 14;100(5):490–5. Scolnick B, Mostofsky DI. Anorexia nervosa: A rogue hibernation? Med Hypotheses. Elsevier Ltd; 2014 Feb;82(2):231–5. Scuteri A, Sanna S, Chen W-M, Uda M, Albai G, Strait J, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007 Jul;3(7):e115. Silventoinen K, Kaprio J. Genetics of tracking of body mass index from birth to late middle age: evidence from twin and family studies. Eur J Obes. 2009 Jan;2(3):196–202. Silventoinen K, Rokholm B, Kaprio J, S?rensen TIA. The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies. Int J Obes. 2010 Jan;34:29–40. Simpson KJ. Anorexia nervosa and culture. J Psychiatr Ment Health Nurs. 2002 Feb;9(1):65–71. Slof-Op ’t Landt MCT, van Furth EF, Meulenbelt I, Slagboom PE, Bartels M, Boomsma DI, et al. Eating disorders: from twin studies to candidate genes and beyond. Twin Res Hum Genet. 2005 Oct;8(5):467–82. Slof-Op ’t Landt MCT, Meulenbelt I, Bartels M, Suchiman E, Middeldorp CM, Houwing-Duistermaat JJ, et al. Association study in eating disorders: TPH2 associates with anorexia nervosa and self-induced vomiting. Genes Brain Behav. 2011 Mar;10(2):236–43. Smink FRE, van Hoeken D, Hoek HW. Epidemiology of eating disorders: incidence, prevalence and mortality rates. Curr Psychiatry Rep. 2012 Aug;14(4):406–14. Smith DE, Marcus MD, Lewis CE, Fitzgibbon M, Schreiner P. Prevalence of binge eating disorder, obesity, and depression in a biracial cohort of young adults. Ann Behav Med. 1998 Jan;20(3):227–32. Smitka K, Papezova H, Vondra K, Hill M, Hainer V, Nedvidkova J. The role of “mixed” orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: Relevance to food intake and nutritional status in patients with anorexia nervosa. Int J Endocrinol. 2013 Jan;2013:483145. Smolak L, Murnen SK. A meta-analytic examination of the relationship between child sexual abuse and eating disorders. Int J Eat Disord. 2002;31(2):559–74. S?dersten P, Nerg?rdh R, Bergh C, Zandian M, Scheurink A. Behavioral neuroendocrinology and treatment of anorexia nervosa. Front Neuroendocrinol. 2008 Oct;29(4):445–62. Son E Van, Hoeken D Van, Bartelds AIM, Furth EF Van, Hoek HW. Time trends in the incidence of eating disorders: A primary care study in the Netherlands. Int J Eat Disord. 2006;39:565–9. Speakman JR. A nonadaptive scenario explaining the genetic predisposition to obesity: the “predation release” hypothesis. Cell Metab. 2007 Jul;6(1):5–12. Speakman JR. Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the “drifty gene” hypothesis. Int J Obes. 2008 Nov;32(11):1611–7. Speakman JR, O’Rahilly S. Fat: an evolving issue. Dis Model Mech. 2012 Sep;5(5):569–73. Speakman JR, Rance K a, Johnstone AM. Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity. 2008 Aug;16:1961–5. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010 Nov;42(11):937–48. Spitzer R., Devlin M, Walsh TB, Hasin DS, Wing R, Marcus M, et al. Binge eating disorder: A multisite field trial of the diagnostic criteria. Int J Eat Disord. 1992;11:191–204. Spitzer R., Yanovski SZ, Wadden T, Wing R, Marcus MD, Stunkard A., et al. Binge eating disorder: Its further validation in a multi-site study. Int J Eat Disord. 1993;13:137–54. Van Spronsen FJ. Phenylketonuria: a 21st century perspective. Nat Rev Endrocrinol. 2010;6:509–14. Spurrell EB, Wilfley DE, Tanofsky MB, Brownell KD. Age of onset for binge eating: are there different pathways to binge eating? Int J Eat Disord. 1997 Jan;21(1):55–65. Sternheim L, Danner U, Adan R, van Elburg A. Drive for activity in patients with anorexia nervosa. Int J Eat iDsorders. 2014 Mar 29;0(00):1–4. St?ger R. The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes? BioEssays. 2008 Feb;30(2):156–66. Striegel-Moore RH, Dohm F a, Kraemer HC, Taylor CB, Daniels S, Crawford PB, et al. Eating disorders in white and black women. Am J Psychiatry. 2003 Jul;160(7):1326–31. Strober M, Freeman R, Lampert C, Diamond J, Kaye W. Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes. Am J Psychiatry. 2000 Mar;157(3):393–401. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The body mass index of twins who have been reared apart. N Engl J Med. 1990;322:1483–7. Stutzmann F, Cauchi S, Durand E, Calvacanti-Proen?a C, Pigeyre M, Hartikainen A-L, et al. Common genetic variation near MC4R is associated with eating behaviour patterns in European populations. Int J Obes. 2009 Mar;33(3):373–8. Stutzmann F, Cauchi S, Durand E, Pigeyre M, Hartikainen A, Sheehy AM, et al. The disease burden associated with overweight and obesity. Int J Obes. Elsevier Ltd; 2011 Jan 12;282(1):1523–9. Stutzmann F, Vatin V, Cauchi S, Morandi A, Jouret B, Landt O, et al. Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene. Hum Mol Genet. 2007 Aug 1;26(15):1837–44. Surbey MK. Anorexia nervosa, amenorrhea, and adaptation. Ethol Sociobiol. 1987;8:47–61. Swinburn B a, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. Elsevier Ltd; 2011 Aug 27;378(9793):804–14. Tan L-J, Zhu H, He H, Wu K-H, Li J, Chen X-D, et al. Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries. PLoS One. 2014 Jan;9(5):e96149. Tanaka T, Ngwa JS, van Rooij FJ a, Zillikens MC, Wojczynski MK, Frazier-Wood AC, et al. Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake. Am J Clin Nutr. 2013 Jun;97:1395–402. Tanofsky-Kraff M, Han JC, Anandalingam K, Shomaker LB, Columbo KM, Wolkoff LE, et al. The FTO gene rs9939609 obesity-risk allele and loss of control over eating. Am J Clin Nutr. 2009;90:1483–8. Taylor JY, Caldwell CH, Baser RE, Matuski N, Faison N, Jackson JS. Classification and correlates of eating disorders among blacks: Findings from the National Survey of American Life. J Heal Care Poor Underserved. 2013;24(1):289–310. Teare MD, Barrett J. Genetic Epidemiology 2: Genetic linkage studies. Lancet. 2005;366:1036–44. Teucher B, Skinner J, Skidmore PML, Cassidy A, Fairweather-Tait SJ, Hooper L, et al. Dietary patterns and heritability of food choice in a UK female twin cohort. Twin Res Hum Genet. 2007 Oct;10(5):734–48. Tholin S, Rasmussen F, Tynelius P, Karlsson J. Genetic and environmental influences on eating behavior: the Swedish Young Male Twins Study. Am J Clin Nutr. 2005 Mar;81:564–9. Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet. 2009 Jan;41(1):18–24. Thornton LM, Mazzeo SE, Bulik CM. The heritability of eating disorders: Methods and current findings. Curr Top Behav Neurosci. 2011;6:141–56. Timpson NJ, Emmett PM, Frayling TM, Rogers I, Hattersley AT, McCarthy MI, et al. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr. 2008 Oct;88(4):971–8. Trace SE, Baker JH, Pe?as-Lledó E, Bulik CM. The genetics of eating disorders. Annu Rev Clin Psychol. 2013 Jan;9:589–620. Tung Y-CL, Yeo GSH. From GWAS to biology: lessons from FTO. Ann N Y Acad Sci. 2011 Mar;1220:162–71. Urwin RE, Bennetts B, Wilcken B, Lampropoulos B, Beumont P, Clarke S, et al. Anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region. Mol Psychiatry. 2002 Jan;7(6):652–7. Valette M, Bellisle F, Carette C, Poitou C, Dubern B, Paradis G, et al. Eating behaviour in obese patients with melanocortin-4 receptor mutations: a literature review. Int J Obes. 2013 a Aug;37(8):1027–35. Valette M, Poitou C, Kesse-Guyot E, Bellisle F, Carette C, Le Beyec J, et al. Association between melanocortin-4 receptor mutations and eating behaviors in obese patients: a case-control study. Int J Obes. 2013 b Oct 9;38(6):883–5. Velders FP, De Wit JE, Jansen PW, Jaddoe VW V, Hofman A, Verhulst FC, et al. FTO at rs9939609, food responsiveness, emotional control and symptoms of ADHD in preschool children. PLoS One. 2012 Jan;7(11):e49131. Vink T, Hinney A, van Elburg AA, van Goozen SH, Sandkuijl LA, Sinke RJ, et al. Association between an agouti-related protein gene polymorphism and anorexia nervosa. Mol Psychiatry. 2001 May;6(3):325–8. Vinkhuyzen AA, Wrap NR, Yang J, Goddard ME, Visscher PM. Estimation and partioning of heritability in human populations using whole genome analysis methods. Annu Rev Genet. 2014;47:75–95. Wade TD, Bergin JL, Tiggemann M, Bulik CM, Fairburn CG. Prevalence and long-term course of lifetime eating disorders in an adult Australian twin cohort. Aust N Z J Psychiatry. 2006 Jan;40(2):121–8. Wang G, Volkow ND, Thanos PK, Fowler JS. Similarity between obesity and drug addiction as assessed by neurofunctional imaging. J Addict Dis. 2004;23(3):39–53. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, et al. Brain dopamine and obesity. Lancet. 2001 Feb 3;357(9253):354–7. Wardle J, Carnell S, Haworth CM a, Farooqi IS, O’Rahilly S, Plomin R. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab. 2008 Sep;93:3640–3. Wardle J, Cooke L. Genetic and environmental determinants of children’s food preferences. Brit J Nutr. 2008 Mar;99 Suppl 1:S15–21. Wardle J, Llewellyn C, Sanderson S, Plomin R. The FTO gene and measured food intake in children. Int J Obes. 2009 Jan;33:42–5. Wasser SK, Barash DP. Reproductive suppression among female mammals: implications for biomedicine and sexual selection theory. Q Rev Biol. 1983 Dec;58(4):513–38. Wei Z, Wang K, Qu H-Q, Zhang H, Bradfield J, Kim C, et al. From disease association to risk assessment: an optimistic view from genome-wide association studies on type 1 diabetes. PLoS Genet. 2009 Oct;5(10):e1000678. Wellman PJ. Norepinephrine and the control of food intake. Nutrition. 2000 Oct;16(10):837–42. Wells JCK. The evolution of human fatness and susceptibility to obesity: an ethological approach. Biol Rev. 2006 May;81(2):183–205. Wells JE, Oakley Browne M a., Scott KM, McGee M a., Baxter J, Kokaua J. Prevalence, interference with life and severity of 12 month DSM-IV disorders in Te Rau Hinengaro: The New Zealand Mental Health Survey. Aust N Z J Psychiatry. 2006 Jan;40(10):845–54. Willer CJ, Speliotes EK, Loos RJF, Li S, Lindgren CM, Heid IM, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009 Jan;41(1):25–34. Willett W, Stampfer MJ. Re: “Total energy intake: implications for epidemiologic analyses”. Am J Epidemiol. 1986 Apr 1;124(1):17–27. Wolfe BE, Baker CW, Smith AT, Kelly-Weeder S. Validity and utility of the current definition of binge eating. Int J Eat Disord. 2009 Dec;42(8):674–86. World Health Organization. Please see the Table of Contents for access to the PDF files. Wyatt HR. Update on treatment strategies for obesity. J Clin Endocrinol Metab. 2013 Apr;98(4):1299–306. Yang J, Benyamin B, McEvoy BP, Gordon S, Henders AK, Nyholt DR, et al. Common SNPs explain a large proportion of the heritability for human height. Nat Genet. 2010 Jul;42(7):565–9. Yanovski SZ. Binge eating disorder and obesity in 2003: could treating an eating disorder have a positive effect on the obesity epidemic? Int J Eat Disord. 2003 Jan;34 Suppl:S117–120. Young LR, Nestle M. The contribution of expanding portion sizes to the US obesity epidemic. Am J Public Health. 2002 Mar;92(2):246–9. Yu W, Clyne M, Yesupriya A, Khoury MJ. A navigator for human genome epidemiology. Nat Genet. 2008;40(2):124–5. Zegers D, Beckers S, Hendrickx R, Van Camp JK, de Craemer V, Verrijken A, et al. Mutation screen of the SIM1 gene in pediatric patients with early-onset obesity. Int J Obes. Nature Publishing Group; 2014 Jul;38(7):1000–4. Zhao W, Wineinger NE, Tiwari HK, Mosley TH, Broeckel U, Arnett DK, et al. Copy number variations associated with obesity-related traits in African Americans: a joint analysis between GENOA and HyperGEN. Obesity (Silver Spring). Nature Publishing Group; 2012 Dec;20(12):2431–7. Zhu M, Zhao S. Candidate gene identification approach: progress and challenges. Int J Biol Sci. 2007 Jan;3(7):420–7. ................
................

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

Google Online Preview   Download