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

  • Elizabeth K. Speliotes
  • , Cristen J. Willer
  • , Sonja I. Berndt
  • , Keri L. Monda
  • , Gudmar Thorleifsson
  • , Anne U. Jackson
  • , Hana Lango Allen
  • , Cecilia M. Lindgren
  • , Jian'An Luan
  • , Reedik Mägi
  • , Joshua C. Randall
  • , Sailaja Vedantam
  • , Thomas W. Winkler
  • , Lu Qi
  • , Tsegaselassie Workalemahu
  • , Iris Heid
  • , Valgerdur Steinthorsdottir
  • , Heather Stringham
  • , Michael N. Weedon
  • , Eeleanor Wheeler
  • Andrew R. Wood, Teresa Ferreira, Robert J. Weyant, Ayellet V. Segrè, Karol Eestrada, Liming Liang, James Nemesh, Ju Hyun Park, Stefan Gustafsson, Tuomas O. Kilpeläinen, Jian Yang, Nabila Bouatia-Naji, Tõnu Eesko, Mary F. Feitosa, Zoltán Kutalik, Massimo Mangino, Soumya Raychaudhuri, Andre Scherag, Albert Vernon Smith, Ryan Welch, Jing Hua Zhao, Katja K. Aben, Devin M. Absher, Najaf Amin, Anna L. Dixon, Eeva Fisher, Nicole Glazer, Michael E. Goddard, Nancy Heard-Costa, Volker Hoesel, Jouke Jan Hottenga, Åsa Johansson, Toby Johnson, Shamika Ketkar, Claudia Lamina, Shengxu Li, Miriam F. Moffatt, Richard H. Myers, Narisu Narisu, John R.B. Perry, Marjolein J. Peters, Micheal Preuss, Samuli Ripatti, Fernando Rivadeneira, Camilla Sandholt, Laura J. Scott, Nicholas J. Timpson, Jonathan P. Tyrer, Sophie Van Wingerden, Richard Watanabe, Charles C. White, Fredrik Wiklund, Christina Barlassina, Daniel I. Chasman, Matthew N. Cooper, John Olov Jansson, Robert W. Lawrence, Niina Pellikka, Inga Prokopenko, Jianxin Shi, Eelisabeth Thiering, Helene Alavere, Maria T.S. Alibrandi, Peter Almgren, Alice Arnold, Thor Aspelund, Larry D. Atwood, Beverley Balkau, Anthony J. Balmforth, Amanda J. Bennett, Yoav Ben-Shlomo, Richard Bergman, Sven Bergmann, Heike Biebermann, Alexandra I.F. Blakemore, Tanja Boes, Lori Bonnycastle, Stefan R. Bornstein, Morris J. Brown, Thomas A. Buchanan, Fabio Busonero, Harry Campbell, Francesco P. Cappuccio, Christine Cavalcanti-Proença, Yii Dder Ida Chen, Chih Mei Chen, Peter Chines, Robert Clarke, Lachlan Coin, John Connell, Ian Day, Martin Den Heijer, Jubao Duan, Shah Eebrahim, Paul Eelliott, Roberto Eelosua, Gudny Eeiriksdottir, Micheal R. Eerdos, Johan G. Eeriksson, Maurizio F. Facheris, Stephan B. Felix, Pamela Fischer-Posovszky, Aaron R. Folsom, Nele Friedrich, Nelson B. Freimer, Mao Fu, Stefan Gaget, Pablo V. Gejman, Eeco J. Geus, Christian Gieger, Anette P. Gjesing, Anuj Goel, Philippe Goyette, Harald Grallert, Jürgen Gräßler, Danielle Greenawalt, Christopher J. Groves, Vilmundur Gudnason, Candace Guiducci, Anna Lliisa Hartikainen, Neelam Hassanali, Alistair Hall, Aki Havulinna, Caroline Hayward, Andrew Heath, Christian Hengstenberg, Andrew A. Hicks, Anke Hinney, Albert Hofman, Georg Homuth, Jennie Hui, Wilmar Igl, Carlos Iribarren, Bo Isomaa, Kevin B. Jacobs, Ivonne Jarick, Eelizabeth Jewell, Ulrich John, Torben Jørgensen, Pekka Jousilahti, Antti Jula, Marika Kaakinen, Eeero Kajantie, Lee Kaplan, Sekar Kathiresan, Johannes Kettunen, Leena Kinnunen, Joshua Knowles, Ivana Kolcic, Inke R. König, Seppo Koskinen, Peter Kovacs, Johanna Kusisto, Peter Kraft, Kirsti Kvaløy, Jaana Laitinen, Olivier Lantieri, Chiara Lanzani, Lenore J. Launer, Cecile Lecoeur, Terho Lehtimäki, Guillaume Lettre, Jianjun Liu, Marja Lissa Lokki, Mattias Lorentzon, Robert Luben, Barbara Ludwig, Magic, Paolo Manunta, Diana Marek, Michel Marre, Nicholas G. Martin, Wendy McArdle, Anne McCarthy, Barbara McKnight, Thomas Meitinger, Olle Melander, David Meyre, Kristian Midthjell, Grant Montgomery, Mario A. Morken, Andrew P. Morris, Rosanda Mulic, Julius Ngwa, Mari Nelis, Matt J. Neville, Dale R. Nyholt, Christopher J. O'Ddonnell, Stephen O'Rahilly, Ken Ong, Ben Ostra, Guillaume Paré, Alex Parker, Markus Perola, Irene Pichler, Kirsi H. Pietiläinen, Carl P. Platou, Ozren Polasek, Anneli Pouta, Suzanne Rafelt, Olli Raitakari, Nigel Rayner, Martin Ridderstråle, Winfried Rief, Aimo Ruokonen, Neil R. Robertson, Peter Rzehak, Veikko Salomaa, Alan R. Sanders, Manjinder Sandhu, Serena Sanna, Jouko Saramies, Markku J. Savolainen, Susann Scherag, Sabine Schipf, Stefan Schreiber, Heribert Schunkert, Kaisa Silander, Juha Sinisalo, David S. Siscovick, Jan H. Smit, Nicole Soranzo, Ulla Sovio, Jonathan Stephens, Ida Surakka, Amy J. Swift, Mari Lliis Tammesoo, Jean Claude Tardif, Maris Teder-Laving, Tanya Teslovich, John R. Thompson, Brian Thomson, Anke Tönjes, Tiinamaija Tuomi, Joyce B.J. Van Meurs, Gert Jan Van OMen, Vincent Vatin, Jorma Viikari, Sophie Visvikis-Siest, Veronique Vitart, Carla I. Vogel, Benjamin F. Voight, Lindsay Waite, Henri Wallaschofski, Bragi Walters, Elisabeth Widen, Susanna Wiegand, Sarah H. Wild, Gonneke Willemsen, Deniel R. Witte, Jacqueline Witteman, Jianfeng Xu, Qunyuan Zhang, Lina Zgaga, Andreas Ziegler, Paavo Zitting, John P. Beilby, I. Ssadaf FarOqi, Johannes Hebebrand, Heikki V. Huikuri, Alan James, Mika Kähönen, Douglas F. Levinson, Fabio MacCiardi, Markku S. Nieminen, Claes Ohlsson, Lyle J. Palmer, Paul Ridker, Micheal Stumvoll, Jacques Beckmann, Heiner Boeing, Eeric Boerwinkle, Dorret I. BOmsma, Mark J. Caulfield, Stephan J. Chanock, Francis Collins, L. Adrienne Cupples, George Davey Smith, Jeanette Eerdmann, Philippe Frogue, Henrik Grönberg, Ulf Gyllensten, Per Hall, Torben Hansen, Tamara B. Harris, Andrew T. Hattersley, Richard B. Hayes, Joachim Heinrich, Frank B. Hu, Kristian Hveem, Thomas Illig, Marjo Riitta Jarvelin, Jaakko Kaprio, Fredrik Karpe, Kay Ttee Khaw, Lambertus A. Kiemeney, Heiko Krude, Markku Laakso, Debbie A. Lawlor, Andres Metspalu, Patricia B. Munroe, Willem H. Ouwehand, Oluf Pedersen, Brenda W. Penninx, Annette Peters, Peter P. Pramstaller, Thomas Quertermous, Thomas Reinehr, Aila Rissanen, Igor Rudan, Nilesh J. Samani, Peter E.H. Schwarz, Alan R. Shuldiner, Timothy D. Spector, Jaakko Tuomilehto, Manuela Uda, André Uitterlinden, Timo Valle, Martin Wabitsch, Gérard Waeber, Nicholas J. Wareham, Hugh Watkins, James F. Wilson, Alan F. Wright, M. Ccarola Zillikens, Nilanjan ChatterjE, Steven A. McCarroll, Shaun Purcell, Eric Schadt, Peter Visscher, Themistocles L. Assimes, Ingrid B. Borecki, Panos Deloukas, Caroline S. Fox, Leif C. Groop, Talin Haritunians, David J. Hunter, Robert Kaplan, Karen Mohlke, Jeffrey R. O'ConneL, Leena Peltonen, David SchleSinger, David P. P Strachan, Cornelia Van Duijn, H. Erich Wichmann, Timothy M. Frayling, Unnur Thorsteinsdottir, Gonçalo R. Abecasis, Inês Barroso, Michael Boehnke*, Kari StefanSon, Kari E. North, Mark I. McArthy, Joel N. Hirschhorn, Erik IngelSon, Ruth J.F. Loos
*Corresponding author for this work
  • Broad Institute
  • Massachusetts General Hospital
  • University of Michigan, Ann Arbor
  • National Institutes of Health
  • University of North Carolina at Chapel Hill
  • deCODE Genetics
  • University of Exeter
  • University of Oxford
  • University of Cambridge
  • Boston Children's Hospital
  • University of Regensburg
  • Harvard University
  • Brigham and Women’s Hospital
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • Wellcome Trust Sanger Institute
  • Massachusetts Institute of Technology
  • Erasmus University Rotterdam
  • Netherlands Genomics Initiative
  • Karolinska Institutet
  • Queensland Institute of Medical Research
  • CNRS
  • Université de Lille
  • University of Tartu
  • University of Tartu
  • Washington University St. Louis
  • University of Lausanne
  • Swiss Institute of Bioinformatics
  • King's College London
  • University of Duisburg-Essen
  • Icelandic Heart Association
  • University of Iceland
  • Netherlands Association of Comprehensive Cancer Centres
  • HudsonAlpha Institute for Biotechnology
  • University of Bath, Department of Life Sciences
  • German Institute of Human Nutrition Potsdam-Rehbruecke
  • University of Washington
  • University of Melbourne
  • State Government of Victoria
  • Boston University
  • Technical University of Munich
  • Vrije Universiteit Amsterdam
  • Uppsala University
  • Norwegian University of Science and Technology
  • Queen Mary University of London
  • Innsbruck Medical University
  • Imperial College London
  • University Medical Center Schleswig-Holstein
  • University of Helsinki
  • National Institute for Health and Welfare
  • Novo Nordisk Foundation
  • MRC Centre for Causal Analyses in Translational Epidemiology
  • University of Southern California
  • University of Milan
  • University of Western Australia
  • University of Gothenburg
  • Vita-Salute San Raffaele University
  • Lund University
  • Renal and Cardiovascular Epidemiology
  • University of Leeds
  • University of Bristol
  • Charité – Universitätsmedizin Berlin
  • Technische Universität Dresden
  • National Research Council of Italy
  • University of Edinburgh
  • University of Warwick
  • Cedars-Sinai Medical Center
  • University of Dundee
  • Radboud University Nijmegen
  • NorthShore University HealthSystem
  • London School of Hygiene and Tropical Medicine
  • South Asia Network for Chronic Disease
  • UK Health Security Agency
  • Biomedical Research Networking Center in Epidemiology and Public Health (CiberESP)
  • Helsinki University Hospital
  • Folkhalsan
  • Vaasa Hospital District
  • EURAC Research
  • General Central Hospital
  • University of Greifswald
  • Diabetes and Obesity Unit
  • University of Minnesota Twin Cities
  • University of California at Los Angeles
  • University of Maryland, Baltimore
  • University of Montreal
  • Merck Research Laboratories
  • University of Oulu
  • NHS Lothian
  • Queen Elizabeth II Medical Centre Trust
  • Sir Charles Gairdner Hospital
  • Kaiser Permanente
  • University of California at San Francisco
  • SAIC
  • University of Marburg
  • University of Copenhagen
  • Hospital District of Helsinki and Uusimaa
  • National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
  • Stanford University
  • University of Zagreb
  • Leipzig University
  • University of Eastern Finland
  • Finnish Institute of Occupational Health
  • Institut interrégional pour la Santé (IRSA)
  • Tampere University
  • Agency for Science, Technology and Research, Singapore
  • MAGIC (Meta-Analyses of Glucose and Insulin-related Traits Consortium)
  • Université Paris Cité
  • Université de Lorraine
  • An Bord Taighde Slainte
  • University of Split
  • McMaster University
  • Amgen Incorporated
  • Nord-Trøndelag Health Trust
  • Gen-Info Ltd
  • University of Leicester
  • University of Turku
  • Ludwig Maximilian University of Munich
  • South Karelia Central Hospital
  • Kiel University
  • University of Lübeck
  • VU University Medical Center
  • NHS Blood and Transplant
  • University Hospitals of Leicester NHS Trust
  • Leiden University
  • Institut national de la santé et de la recherche médicale
  • Wake Forest University
  • Lapland Central Hospital
  • University of California at Irvine
  • University of Texas Health Science Center at Houston
  • University of Southern Denmark
  • New York University
  • National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
  • Aarhus University
  • University of Groningen
  • Witten/Herdecke University
  • Department of Veterans Affairs
  • South Ostrobothnia Central Hospital
  • Pacific Biosciences
  • Sage Bionetworks
  • Albert Einstein College of Medicine
  • St. George's University of London

Research output: Contribution to journalArticlepeer-review

Abstract

Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS 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 aSociated loci may provide new insights into human body weight regulation.

Original languageEnglish
Pages (from-to)937-948
Number of pages12
JournalNature Genetics
Volume42
Issue number11
DOIs
Publication statusPublished - 1 Nov 2010
Externally publishedYes

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