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Genetic studies of body mass index yield new insights for obesity biology.

About this Publication
Title
Genetic studies of body mass index yield new insights for obesity biology.
Pubmed ID
25673413 (View this publication on the PubMed website)
Publication
Nature. 2015 Feb; Volume 518 (Issue 7538): Pages 197-206
Authors
Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, Powell C, Vedantam S, Buchkovich ML, Yang J, Croteau-Chonka DC, Esko T, Fall T, Ferreira T, Gustafsson S, Kutalik Z, Luan J, Mägi R, Randall JC, Winkler TW, ...show more Wood AR, Workalemahu T, Faul JD, Smith JA, Zhao JH, Zhao W, Chen J, Fehrmann R, Hedman ÅK, Karjalainen J, Schmidt EM, Absher D, Amin N, Anderson D, Beekman M, Bolton JL, Bragg-Gresham JL, Buyske S, Demirkan A, Deng G, Ehret GB, Feenstra B, Feitosa MF, Fischer K, Goel A, Gong J, Jackson AU, Kanoni S, Kleber ME, Kristiansson K, Lim U, Lotay V, Mangino M, Leach IM, Medina-Gomez C, Medland SE, Nalls MA, Palmer CD, Pasko D, Pechlivanis S, Peters MJ, Prokopenko I, Shungin D, Stančáková A, Strawbridge RJ, Sung YJ, Tanaka T, Teumer A, Trompet S, van der Laan SW, van Setten J, Van Vliet-Ostaptchouk JV, Wang Z, Yengo L, Zhang W, Isaacs A, Albrecht E, Ärnlöv J, Arscott GM, Attwood AP, Bandinelli S, Barrett A, Bas IN, Bellis C, Bennett AJ, Berne C, Blagieva R, Blüher M, Böhringer S, Bonnycastle LL, Böttcher Y, Boyd HA, Bruinenberg M, Caspersen IH, Chen YI, Clarke R, Daw EW, de Craen AJM, Delgado G, Dimitriou M, Doney ASF, Eklund N, Estrada K, Eury E, Folkersen L, Fraser RM, Garcia ME, Geller F, Giedraitis V, Gigante B, Go AS, Golay A, Goodall AH, Gordon SD, Gorski M, Grabe HJ, Grallert H, Grammer TB, Gräßler J, Grönberg H, Groves CJ, Gusto G, Haessler J, Hall P, Haller T, Hallmans G, Hartman CA, Hassinen M, Hayward C, Heard-Costa NL, Helmer Q, Hengstenberg C, Holmen O, Hottenga JJ, James AL, Jeff JM, Johansson Å, Jolley J, Juliusdottir T, Kinnunen L, Koenig W, Koskenvuo M, Kratzer W, Laitinen J, Lamina C, Leander K, Lee NR, Lichtner P, Lind L, Lindström J, Lo KS, Lobbens S, Lorbeer R, Lu Y, Mach F, Magnusson PKE, Mahajan A, McArdle WL, McLachlan S, Menni C, Merger S, Mihailov E, Milani L, Moayyeri A, Monda KL, Morken MA, Mulas A, Müller G, Müller-Nurasyid M, Musk AW, Nagaraja R, Nöthen MM, Nolte IM, Pilz S, Rayner NW, Renstrom F, Rettig R, Ried JS, Ripke S, Robertson NR, Rose LM, Sanna S, Scharnagl H, Scholtens S, Schumacher FR, Scott WR, Seufferlein T, Shi J, Smith AV, Smolonska J, Stanton AV, Steinthorsdottir V, Stirrups K, Stringham HM, Sundström J, Swertz MA, Swift AJ, Syvänen AC, Tan ST, Tayo BO, Thorand B, Thorleifsson G, Tyrer JP, Uh HW, Vandenput L, Verhulst FC, Vermeulen SH, Verweij N, Vonk JM, Waite LL, Warren HR, Waterworth D, Weedon MN, Wilkens LR, Willenborg C, Wilsgaard T, Wojczynski MK, Wong A, Wright AF, Zhang Q, LifeLines Cohort Study, Brennan EP, Choi M, Dastani Z, Drong AW, Eriksson P, Franco-Cereceda A, Gådin JR, Gharavi AG, Goddard ME, Handsaker RE, Huang J, Karpe F, Kathiresan S, Keildson S, Kiryluk K, Kubo M, Lee JY, Liang L, Lifton RP, Ma B, McCarroll SA, McKnight AJ, Min JL, Moffatt MF, Montgomery GW, Murabito JM, Nicholson G, Nyholt DR, Okada Y, Perry JRB, Dorajoo R, Reinmaa E, Salem RM, Sandholm N, Scott RA, Stolk L, Takahashi A, Tanaka T, van 't Hooft FM, Vinkhuyzen AAE, Westra HJ, Zheng W, Zondervan KT, ADIPOGen Consortium, AGEN-BMI Working Group, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GLGC, ICBP, MAGIC Investigators, MuTHER Consortium, MIGen Consortium, PAGE Consortium, ReproGen Consortium, GENIE Consortium, International Endogene Consortium, Heath AC, Arveiler D, Bakker SJL, Beilby J, Bergman RN, Blangero J, Bovet P, Campbell H, Caulfield MJ, Cesana G, Chakravarti A, Chasman DI, Chines PS, Collins FS, Crawford DC, Cupples LA, Cusi D, Danesh J, de Faire U, den Ruijter HM, Dominiczak AF, Erbel R, Erdmann J, Eriksson JG, Farrall M, Felix SB, Ferrannini E, Ferrières J, Ford I, Forouhi NG, Forrester T, Franco OH, Gansevoort RT, Gejman PV, Gieger C, Gottesman O, Gudnason V, Gyllensten U, Hall AS, Harris TB, Hattersley AT, Hicks AA, Hindorff LA, Hingorani AD, Hofman A, Homuth G, Hovingh GK, Humphries SE, Hunt SC, Hyppönen E, Illig T, Jacobs KB, Jarvelin MR, Jöckel KH, Johansen B, Jousilahti P, Jukema JW, Jula AM, Kaprio J, Kastelein JJP, Keinanen-Kiukaanniemi SM, Kiemeney LA, Knekt P, Kooner JS, Kooperberg C, Kovacs P, Kraja AT, Kumari M, Kuusisto J, Lakka TA, Langenberg C, Marchand LL, Lehtimäki T, Lyssenko V, Männistö S, Marette A, Matise TC, McKenzie CA, McKnight B, Moll FL, Morris AD, Morris AP, Murray JC, Nelis M, Ohlsson C, Oldehinkel AJ, Ong KK, Madden PAF, Pasterkamp G, Peden JF, Peters A, Postma DS, Pramstaller PP, Price JF, Qi L, Raitakari OT, Rankinen T, Rao DC, Rice TK, Ridker PM, Rioux JD, Ritchie MD, Rudan I, Salomaa V, Samani NJ, Saramies J, Sarzynski MA, Schunkert H, Schwarz PEH, Sever P, Shuldiner AR, Sinisalo J, Stolk RP, Strauch K, Tönjes A, Trégouët DA, Tremblay A, Tremoli E, Virtamo J, Vohl MC, Völker U, Waeber G, Willemsen G, Witteman JC, Zillikens MC, Adair LS, Amouyel P, Asselbergs FW, Assimes TL, Bochud M, Boehm BO, Boerwinkle E, Bornstein SR, Bottinger EP, Bouchard C, Cauchi S, Chambers JC, Chanock SJ, Cooper RS, de Bakker PIW, Dedoussis G, Ferrucci L, Franks PW, Froguel P, Groop LC, Haiman CA, Hamsten A, Hui J, Hunter DJ, Hveem K, Kaplan RC, Kivimaki M, Kuh D, Laakso M, Liu Y, Martin NG, März W, Melbye M, Metspalu A, Moebus S, Munroe PB, Njølstad I, Oostra BA, Palmer CNA, Pedersen NL, Perola M, Pérusse L, Peters U, Power C, Quertermous T, Rauramaa R, Rivadeneira F, Saaristo TE, Saleheen D, Sattar N, Schadt EE, Schlessinger D, Slagboom PE, Snieder H, Spector TD, Thorsteinsdottir U, Stumvoll M, Tuomilehto J, Uitterlinden AG, Uusitupa M, van der Harst P, Walker M, Wallaschofski H, Wareham NJ, Watkins H, Weir DR, Wichmann HE, Wilson JF, Zanen P, Borecki IB, Deloukas P, Fox CS, Heid IM, O'Connell JR, Strachan DP, Stefansson K, van Duijn CM, Abecasis GR, Franke L, Frayling TM, McCarthy MI, Visscher PM, Scherag A, Willer CJ, Boehnke M, Mohlke KL, Lindgren CM, Beckmann JS, Barroso I, North KE, Ingelsson E, Hirschhorn JN, Loos RJF, Speliotes EK
Affiliations
  • Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
  • Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
  • MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
  • Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
...show more
  • Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden.
  • Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne 1010, Switzerland.
  • Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
  • Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, D-93053 Regensburg, Germany.
  • Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
  • Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
  • Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48104, USA.
  • Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
  • Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA.
  • Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC University Medical Center, 3015 GE Rotterdam, The Netherlands.
  • Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia 6008, Australia.
  • Netherlands Consortium for Healthy Aging (NCHA), Leiden University Medical Center, Leiden 2300 RC, The Netherlands.
  • Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
  • Department of Statistics & Biostatistics, Rutgers University, Piscataway, New Jersey 08854, USA.
  • Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK.
  • Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  • Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, Denmark.
  • Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
  • William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, D-68187 Mannheim, Germany.
  • National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
  • Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
  • The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
  • Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
  • Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.
  • Netherlands Consortium for Healthy Aging (NCHA), 3015GE Rotterdam, The Netherlands.
  • QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
  • Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University Hospital Essen, 45147 Essen, Germany.
  • Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hosptial, Malmö 205 02, Sweden.
  • University of Eastern Finland, FI-70210 Kuopio, Finland.
  • Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
  • Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
  • Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland 21225, USA.
  • Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17475 Greifswald, Germany.
  • Department of Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
  • Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Department of Medical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
  • CNRS UMR 8199, F-59019 Lille, France.
  • Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
  • PathWest Laboratory Medicine of Western Australia, Nedlands, Western Australia 6009, Australia.
  • Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK.
  • Geriatric Unit, Azienda Sanitaria Firenze (ASF), 50125 Florence, Italy.
  • Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK.
  • USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City 6000, Philippines.
  • Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas 78227, USA.
  • Department of Medical Sciences, Endocrinology, Diabetes and Metabolism, Uppsala University, Uppsala 75185, Sweden.
  • Division of Endocrinology, Diabetes and Metabolism, Ulm University Medical Centre, D-89081 Ulm, Germany.
  • Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, D-04103 Leipzig, Germany.
  • Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA.
  • LifeLines Cohort Study, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
  • Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
  • Department of Pediatrics, University of California Los Angeles, Torrance, California 90502, USA.
  • Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.
  • Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
  • Department of Dietetics-Nutrition, Harokopio University, 17671 Athens, Greece.
  • Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
  • Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.
  • Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Bethesda, Maryland 20892, USA.
  • Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala 75185, Sweden.
  • Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Stockholm 17177, Sweden.
  • Kaiser Permanente, Division of Research, Oakland, California 94612, USA.
  • Service of Therapeutic Education for Diabetes, Obesity and Chronic Diseases, Geneva University Hospital, Geneva CH-1211, Switzerland.
  • Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.
  • Department of Psychiatry and Psychotherapy, University Medicine Greifswald, HELIOS-Hospital Stralsund, D-17475 Greifswald, Germany.
  • Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
  • Institut inter Régional pour la Santé, Synergies, F-37520 La Riche, France.
  • Department of Public Health and Clinical Medicine, Unit of Nutritional Research, Umeå University, Umeå 90187, Sweden.
  • Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700RB Groningen, The Netherlands.
  • Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland.
  • MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
  • National Heart, Lung, and Blood Institute, the Framingham Heart Study, Framingham, Massachusetts 01702, USA.
  • Deutsches Forschungszentrum für Herz-Kreislauferkrankungen (DZHK) (German Research Centre for Cardiovascular Research), Munich Heart Alliance, D-80636 Munich, Germany.
  • Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim 7489, Norway.
  • Biological Psychology, VU University Amsterdam, 1081BT Amsterdam, The Netherlands.
  • Department of Pulmonary Physiology and Sleep Medicine, Nedlands, Western Australia 6009, Australia.
  • Uppsala University, Department of Immunology, Genetics, Pathology, SciLifeLab, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden.
  • Department of Internal Medicine II, Ulm University Medical Centre, D-89081 Ulm, Germany.
  • Hjelt Institute Department of Public Health, University of Helsinki, FI-00014 Helsinki, Finland.
  • Department of Internal Medicine I, Ulm University Medical Centre, D-89081 Ulm, Germany.
  • Finnish Institute of Occupational Health, FI-90100 Oulu, Finland.
  • Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria.
  • Institute of Human Genetics, Helmholtz Zentrum München - German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
  • Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala 75185, Sweden.
  • Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada.
  • Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany.
  • Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva 1211, Switzerland.
  • School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.
  • Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cagliari, Sardinia 09042, Italy.
  • Center for Evidence-based Healthcare, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
  • Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia.
  • Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA.
  • Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany.
  • Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
  • Department of Epidemiology and Biostatistics, Institute for Research in Extramural Medicine, Institute for Health and Care Research, VU University Medical Center, 1081BT Amsterdam, The Netherlands.
  • Institute of Physiology, University Medicine Greifswald, D-17495 Karlsburg, Germany.
  • Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
  • Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
  • National Cancer Institute, Bethesda, Maryland 20892, USA.
  • Icelandic Heart Association, Kopavogur 201, Iceland.
  • Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
  • deCODE Genetics, Amgen Inc., Reykjavik 101, Iceland.
  • Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  • Department of Public Health Sciences, Stritch School of Medicine, Loyola University of Chicago, Maywood, Illinois 61053, USA.
  • German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
  • Department of Oncology, University of Cambridge, Cambridge CB2 0QQ, UK.
  • Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg 413 45, Sweden.
  • Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC University Medical Centre, 3000 CB Rotterdam, The Netherlands.
  • Department for Health Evidence, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
  • Department of Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Genetics, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA.
  • German Center for Cardiovascular Research, partner site Hamburg/Lubeck/Kiel, 23562 Lubeck, Germany.
  • Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037 Tromsø, Norway.
  • MRC Unit for Lifelong Health and Ageing at University College London, London WC1B 5JU, UK.
  • Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland.
  • Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
  • Lady Davis Institute, Departments of Human Genetics, Epidemiology and Biostatistics, McGill University, Montréal, Québec H3T1E2, Canada.
  • Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 17176, Sweden.
  • Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
  • Biosciences Research Division, Department of Primary Industries, Victoria 3083, Australia.
  • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
  • Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
  • Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Chungbuk 363-951, Republic of Korea.
  • Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, New Haven, Connecticut 06520, USA.
  • Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, County Down BT9 7AB, UK.
  • National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK.
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
  • Genome Institute of Singapore, Agency for Science, Technology and Research, 138672 Singapore.
  • Department of Biomedical Engineering and Computational Science, Aalto University School of Science, Helsinki FI-00076, Finland.
  • Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan.
  • Division of Epidemiology, Department of Medicine; Vanderbilt Epidemiology Center; and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37075, USA.
  • Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA.
  • Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France.
  • Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9700RB Groningen, The Netherlands.
  • Cedars-Sinai Diabetes and Obesity Research Institute, Los Angeles, California 90048, USA.
  • Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1010 Lausanne, Switzerland.
  • University of Milano, Bicocca, 20126, Italy.
  • Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
  • Department of Health Sciences, University of Milano, I 20142, Italy.
  • Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
  • Clinic of Cardiology, West-German Heart Centre, University Hospital Essen, 45147 Essen, Germany.
  • Department of Internal Medicine B, University Medicine Greifswald, D-17475 Greifswald, Germany.
  • Department of Internal Medicine, University of Pisa, 56100 Pisa, Italy.
  • Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, 31400 Toulouse, France.
  • Robertson Center for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK.
  • UWI Solutions for Developing Countries, The University of the West Indies, Mona, Kingston 7, Jamaica.
  • NorthShore University HealthSystem, Evanston, IL 60201, University of Chicago, Chicago, Illinois, USA.
  • Leeds MRC Medical Bioinformatics Centre, University of Leeds, Leeds LS2 9LU, UK.
  • Institute of Biomedical & Clinical Science, University of Exeter, Barrack Road, Exeter EX2 5DW, UK.
  • Center for Biomedicine, European Academy Bozen, Bolzano (EURAC), Bolzano 39100, Italy (affiliated institute of the University of Lübeck, D-23562 Lübeck, Germany).
  • Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.
  • Department of Vascular Medicine, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
  • Centre for Cardiovascular Genetics, Institute Cardiovascular Sciences, University College London, London WC1E 6JJ, UK.
  • Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84108, USA.
  • Sansom Institute for Health Research, University of South Australia, Adelaide 5000, South Australia, Australia.
  • Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
  • Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK.
  • Institute of Health Sciences, University of Oulu, FI-90014 Oulu, Finland.
  • Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK.
  • Department of Medicine, Kuopio University Hospital and University of Eastern Finland, FI-70210 Kuopio, Finland.
  • Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine University of Tampere, FI-33520 Tampere, Finland.
  • Steno Diabetes Center A/S, Gentofte DK-2820, Denmark.
  • Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculty of Medicine, Laval University, Quebec, QC G1V 0A6, Canada.
  • Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA.
  • Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
  • Department of Surgery, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA.
  • Illumina, Inc, Little Chesterford, Cambridge CB10 1XL, UK.
  • University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine and Tuberculosis, Groningen, The Netherlands.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, FI-20521 Turku, Finland.
  • Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
  • Center for Systems Genomics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
  • South Carelia Central Hospital, 53130 Lappeenranta, Finland.
  • International Centre for Circulatory Health, Imperial College London, London W2 1PG, UK.
  • Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
  • Helsinki University Central Hospital Heart and Lung Center, Department of Medicine, Helsinki University Central Hospital, FI-00290 Helsinki, Finland.
  • Sorbonne Universités, UPMC Univ Paris 06, UMR S 1166, F-75013 Paris, France.
  • Department of Kinesiology, Laval University, Quebec QC G1V 0A6, Canada.
  • Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano & Centro Cardiologico Monzino, Instituto di Ricovero e Cura a Carattere Scientifico, Milan 20133, Italy.
  • Institute of Nutrition and Functional Foods, Laval University, Quebec, QC G1V 0A6, Canada.
  • Department of Internal Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne 1011, Switzerland.
  • Department of Epidemiology, Erasmus MC University Medical Center, 3015GE Rotterdam, The Netherlands.
  • Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
  • Institut Pasteur de Lille; INSERM, U744; Université de Lille 2; F-59000 Lille, France.
  • Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA.
  • Lee Kong Chian School of Medicine, Imperial College London and Nanyang Technological University, Singapore, 637553 Singapore, Singapore.
  • Health Science Center at Houston, University of Texas, Houston, Texas 77030, USA.
  • Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
  • Institute for Molecular Medicine, University of Helsinki, FI-00014 Helsinki, Finland.
  • Albert Einstein College of Medicine, Department of Epidemiology and Population Health, Belfer 1306, New York 10461, USA.
  • Center for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
  • Population, Policy, and Practice, University College London Institute of Child Health, London WC1N 1EH, UK.
  • Finnish Diabetes Association, Kirjoniementie 15, FI-33680 Tampere, Finland.
  • BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK.
  • Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10580, USA.
  • Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
  • Institute of Cellular Medicine, Newcastle University, Newcastle NE1 7RU, UK.
  • DZHK (Deutsches Zentrum für Herz-Kreislaufforschung - German Centre for Cardiovascular Research), partner site Greifswald, D-17475 Greifswald, Germany.
  • Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, D-85764 Munich, Germany.
  • Department of Pulmonology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Division of Population Health Sciences & Education, St George's, University of London, London SW17 0RE, UK.
  • Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

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