{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:15:59Z","timestamp":1792700159736,"version":"4.5.0"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2018,12,25]]},"DOI":"10.1001\/jama.2018.19329","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T11:06:09Z","timestamp":1545390369000},"page":"2553","source":"Crossref","is-referenced-by-count":232,"title":["Association of Genetic Variants Related to Gluteofemoral vs Abdominal Fat Distribution With Type 2 Diabetes, Coronary Disease, and Cardiovascular Risk Factors"],"prefix":"10.1001","volume":"320","author":[{"given":"Luca A.","family":"Lotta","sequence":"first","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura B. L.","family":"Wittemans","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Zuber","sequence":"additional","affiliation":[{"name":"MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isobel D.","family":"Stewart","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Sharp","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2019an","family":"Luan","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix R.","family":"Day","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Bowker","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Cai","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuella","family":"De Lucia Rolfe","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay-Tee","family":"Khaw","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R. B.","family":"Perry","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"O\u2019Rahilly","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Scott","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Savage","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Burgess","sequence":"additional","affiliation":[{"name":"MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom"},{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Wareham","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Langenberg","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"joi180146r1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1093\/ajcn\/4.1.20","article-title":"The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease.","volume":"4","author":"Vague","year":"1956","journal-title":"Am J Clin Nutr"},{"issue":"9497","key":"joi180146r2","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1016\/S0140-6736(05)67663-5","article-title":"Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study.","volume":"366","author":"Yusuf","year":"2005","journal-title":"Lancet"},{"issue":"24","key":"joi180146r3","doi-asserted-by":"publisher","first-page":"2504","DOI":"10.1001\/jama.2010.843","article-title":"Association between adiposity in midlife and older age and risk of diabetes in older adults.","volume":"303","author":"Biggs","year":"2010","journal-title":"JAMA"},{"issue":"6","key":"joi180146r4","doi-asserted-by":"publisher","first-page":"e1001230","DOI":"10.1371\/journal.pmed.1001230","article-title":"Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-InterAct case-cohort study.","volume":"9","author":"Langenberg","year":"2012","journal-title":"PLoS Med"},{"issue":"2","key":"joi180146r5","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/S2213-8587(13)70062-7","article-title":"Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications.","volume":"1","author":"Stefan","year":"2013","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"12","key":"joi180146r6","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1056\/NEJMra025261","article-title":"Acquired and inherited lipodystrophies.","volume":"350","author":"Garg","year":"2004","journal-title":"N Engl J Med"},{"issue":"4","key":"joi180146r7","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1210\/er.2010-0020","article-title":"Genetic syndromes of severe insulin resistance.","volume":"32","author":"Semple","year":"2011","journal-title":"Endocr Rev"},{"issue":"2","key":"joi180146r8","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/nrendo.2014.185","article-title":"Biology of upper-body and lower-body adipose tissue: link to whole-body phenotypes.","volume":"11","author":"Karpe","year":"2015","journal-title":"Nat Rev Endocrinol"},{"issue":"10","key":"joi180146r9","doi-asserted-by":"publisher","first-page":"E1870","DOI":"10.1210\/jc.2014-1526","article-title":"Adipose tissue and metabolic alterations: regional differences in fat cell size and number matter, but differently: a cross-sectional study.","volume":"99","author":"Ryd\u00e9n","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"joi180146r10","doi-asserted-by":"publisher","first-page":"433","DOI":"10.2337\/db15-0828","article-title":"Numerous genes in loci associated with body fat distribution are linked to adipose function.","volume":"65","author":"Dahlman","year":"2016","journal-title":"Diabetes"},{"issue":"1","key":"joi180146r11","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/ng.3714","article-title":"Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.","volume":"49","author":"Lotta","year":"2017","journal-title":"Nat Genet"},{"issue":"12","key":"joi180146r12","doi-asserted-by":"publisher","first-page":"4378","DOI":"10.2337\/db14-0319","article-title":"Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity.","volume":"63","author":"Scott","year":"2014","journal-title":"Diabetes"},{"issue":"12","key":"joi180146r13","doi-asserted-by":"publisher","first-page":"4369","DOI":"10.2337\/db14-0318","article-title":"Genetic evidence for a normal-weight \u201cmetabolically obese\u201d phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes.","volume":"63","author":"Yaghootkar","year":"2014","journal-title":"Diabetes"},{"issue":"8","key":"joi180146r14","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.2337\/db15-1671","article-title":"Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension, and heart disease.","volume":"65","author":"Yaghootkar","year":"2016","journal-title":"Diabetes"},{"issue":"3","key":"joi180146r15","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age.","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med"},{"issue":"7538","key":"joi180146r16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nature14132","article-title":"New genetic loci link adipose and insulin biology to body fat distribution.","volume":"518","author":"Shungin","year":"2015","journal-title":"Nature"},{"key":"joi180146r17","first-page":"95","article-title":"EPIC-Norfolk: study design and characteristics of the cohort: European Prospective Investigation of Cancer.","volume":"80","author":"Day","year":"1999","journal-title":"Br J Cancer"},{"issue":"9","key":"joi180146r18","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.1007\/s00125-011-2182-9","article-title":"Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study.","volume":"54","author":"Langenberg","year":"2011","journal-title":"Diabetologia"},{"issue":"7538","key":"joi180146r19","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic studies of body mass index yield new insights for obesity biology.","volume":"518","author":"Locke","year":"2015","journal-title":"Nature"},{"issue":"9","key":"joi180146r20","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/ng.2385","article-title":"Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.","volume":"44","author":"Scott","year":"2012","journal-title":"Nat Genet"},{"issue":"6","key":"joi180146r21","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/ng.2274","article-title":"A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.","volume":"44","author":"Manning","year":"2012","journal-title":"Nat Genet"},{"issue":"11","key":"joi180146r22","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1038\/ng.2797","article-title":"Discovery and refinement of loci associated with lipid levels.","volume":"45","author":"Willer","year":"2013","journal-title":"Nat Genet"},{"issue":"9","key":"joi180146r23","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1038\/ng.2383","article-title":"Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.","volume":"44","author":"Morris","year":"2012","journal-title":"Nat Genet"},{"issue":"10","key":"joi180146r24","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/ng.3396","article-title":"A comprehensive 1,000 genomes-based genome-wide association meta-analysis of coronary artery disease.","volume":"47","author":"Nikpay","year":"2015","journal-title":"Nat Genet"},{"issue":"9","key":"joi180146r25","doi-asserted-by":"publisher","first-page":"e0162388","DOI":"10.1371\/journal.pone.0162388","article-title":"Algorithms for the capture and adjudication of prevalent and incident diabetes in UK Biobank.","volume":"11","author":"Eastwood","year":"2016","journal-title":"PLoS One"},{"issue":"6","key":"joi180146r26","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1001\/jama.2016.21042","article-title":"Genetic association of waist-to-hip ratio with cardiometabolic traits, type 2 diabetes, and coronary heart disease.","volume":"317","author":"Emdin","year":"2017","journal-title":"JAMA"},{"issue":"3","key":"joi180146r27","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/ng.3190","article-title":"Efficient Bayesian mixed-model analysis increases association power in large cohorts.","volume":"47","author":"Loh","year":"2015","journal-title":"Nat Genet"},{"issue":"7","key":"joi180146r28","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/s41588-018-0144-6","article-title":"Mixed-model association for Biobank-scale datasets.","volume":"50","author":"Loh","year":"2018","journal-title":"Nat Genet"},{"issue":"17","key":"joi180146r29","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: fast and efficient meta-analysis of genomewide association scans.","volume":"26","author":"Willer","year":"2010","journal-title":"Bioinformatics"},{"issue":"7145","key":"joi180146r30","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.","volume":"447","author":"Wellcome Trust Case Control Consortium","year":"2007","journal-title":"Nature"},{"issue":"2","key":"joi180146r31","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.ajhg.2014.12.021","article-title":"Adjusting for heritable covariates can bias effect estimates in genome-wide association studies.","volume":"96","author":"Aschard","year":"2015","journal-title":"Am J Hum Genet"},{"issue":"4","key":"joi180146r32","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1198\/073500102288618658","article-title":"A survey of weak instruments and weak identification in generalized method of moments.","volume":"20","author":"Stock","year":"2002","journal-title":"J Bus Econ Stat"},{"issue":"7","key":"joi180146r33","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data.","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"issue":"2","key":"joi180146r34","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1534\/genetics.117.300191","article-title":"Dissecting causal pathways using mendelian randomization with summarized genetic data: application to age at menarche and risk of breast cancer.","volume":"207","author":"Burgess","year":"2017","journal-title":"Genetics"},{"issue":"24","key":"joi180146r35","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.1161\/CIRCULATIONAHA.116.026560","article-title":"Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a mendelian randomization analysis.","volume":"135","author":"Dale","year":"2017","journal-title":"Circulation"},{"issue":"1","key":"joi180146r36","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/79111","article-title":"Failure of adipocyte differentiation causes type II diabetes mellitus?","volume":"26","author":"Danforth","year":"2000","journal-title":"Nat Genet"},{"issue":"3","key":"joi180146r37","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.bbalip.2009.12.006","article-title":"Adipose tissue expandability, lipotoxicity and the metabolic syndrome: an allostatic perspective.","volume":"1801","author":"Virtue","year":"2010","journal-title":"Biochim Biophys Acta"},{"issue":"9492","key":"joi180146r38","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1016\/S0140-6736(05)67483-1","article-title":"Obesity.","volume":"366","author":"Haslam","year":"2005","journal-title":"Lancet"},{"issue":"8","key":"joi180146r39","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1038\/ejhg.2015.272","article-title":"Rare variant associations with waist-to-hip ratio in European-American and African-American women from the NHLBI-Exome Sequencing Project.","volume":"24","author":"Kan","year":"2016","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"joi180146r40","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/ng.3738","article-title":"Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.","volume":"49","author":"Chu","year":"2017","journal-title":"Nat Genet"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2719309","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T19:15:24Z","timestamp":1662664524000},"score":1,"resource":{"primary":{"URL":"http:\/\/jama.jamanetwork.com\/article.aspx?doi=10.1001\/jama.2018.19329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,25]]},"references-count":40,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2018,12,25]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2018.19329","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2018,12,25]]}}}