Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

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 ∼ 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 × 10⁻⁸), 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.

Keywords

Affiliated Institutions

• University of Gothenburg SE
• Harvard University US
• The University of Melbourne AU
• King's College London GB
• University of Exeter GB
• Medical Research Council GB
• National Cancer Institute US
• Helmholtz Zentrum München DE
• Charité - Universitätsmedizin Berlin DE
• Norwegian University of Science and Technology
• The University of Western Australia AU
• Broad Institute US
• University of North Carolina at Chapel Hill US
• Technische Universität Dresden DE
• Technical University of Munich DE
• Addenbrooke's Hospital GB
• Netherlands Consortium for Healthy Ageing NL
• Karolinska Institutet SE
• National Human Genome Research Institute US
• Massachusetts General Hospital US
• Centre National de la Recherche Scientifique FR
• deCODE Genetics (Iceland) IS
• University of Duisburg-Essen DE
• Centre for Human Genetics GB
• Institute for Molecular Medicine Finland FI
• QIMR Berghofer Medical Research Institute AU
• University Hospital Schleswig-Holstein DE
• Massachusetts Institute of Technology US
• University of Bath GB
• Finnish Institute for Health and Welfare FI
• Imperial College London GB
• Uppsala University SE
• University of Helsinki FI
• Netherlands Comprehensive Cancer Organisation NL
• Vrije Universiteit Amsterdam NL
• Brigham and Women's Hospital US
• University of Milan IT
• SIB Swiss Institute of Bioinformatics CH
• University of Cambridge GB
• Centre de recherche en Epidémiologie et Santé des Populations FR
• Estonian Biocentre EE
• University of Oxford GB
• Boston University US
• Lund University SE
• Erasmus MC NL
• Erasmus University Rotterdam NL
• University of Bristol GB
• National Institutes of Health US
• Genomics (United Kingdom) GB
• University of Iceland IS
• Icelandic Heart Association IS
• Center for Human Genetics US
• Inserm FR
• Vita-Salute San Raffaele University IT
• Oxford Centre for Diabetes, Endocrinology and Metabolism GB
• Université Lille Nord de France FR
• Institut Pasteur de Lille FR
• HudsonAlpha Institute for Biotechnology US
• University of Michigan US
• University of Lübeck DE
• Peninsula College of Medicine and Dentistry GB
• MRC Epidemiology Unit GB
• Wellcome Sanger Institute GB
• University of Leeds GB
• German Institute of Human Nutrition DE
• University of Southern California US
• University of Tartu EE
• University of Washington US
• Washington University in St. Louis US
• University of Lausanne CH

Related Publications