Genetic studies of body mass index yield new insights for obesity biology View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-02

AUTHORS

Adam E. Locke, Bratati Kahali, Sonja I. Berndt, Anne E. Justice, Tune H. Pers, Felix R. Day, Corey Powell, Sailaja Vedantam, Martin L. Buchkovich, Jian Yang, Damien C. Croteau-Chonka, Tonu Esko, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Zoltán Kutalik, Jian’an Luan, Reedik Mägi, Joshua C. Randall, Thomas W. Winkler, Andrew R. Wood, Tsegaselassie Workalemahu, Jessica D. Faul, Jennifer A. Smith, Jing Hua Zhao, Wei Zhao, Jin Chen, Rudolf Fehrmann, Åsa K. Hedman, Juha Karjalainen, Ellen M. Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Marian Beekman, Jennifer L. Bolton, Jennifer L. Bragg-Gresham, Steven Buyske, Ayse Demirkan, Guohong Deng, Georg B. Ehret, Bjarke Feenstra, Mary F. Feitosa, Krista Fischer, Anuj Goel, Jian Gong, Anne U. Jackson, Stavroula Kanoni, Marcus E. Kleber, Kati Kristiansson, Unhee Lim, Vaneet Lotay, Massimo Mangino, Irene Mateo Leach, Carolina Medina-Gomez, Sarah E. Medland, Michael A. Nalls, Cameron D. Palmer, Dorota Pasko, Sonali Pechlivanis, Marjolein J. Peters, Inga Prokopenko, Dmitry Shungin, Alena Stančáková, Rona J. Strawbridge, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W. van der Laan, Jessica van Setten, Jana V. Van Vliet-Ostaptchouk, Zhaoming Wang, Loïc Yengo, Weihua Zhang, Aaron Isaacs, Eva Albrecht, Johan Ärnlöv, Gillian M. Arscott, Antony P. Attwood, Stefania Bandinelli, Amy Barrett, Isabelita N. Bas, Claire Bellis, Amanda J. Bennett, Christian Berne, Roza Blagieva, Matthias Blüher, Stefan Böhringer, Lori L. Bonnycastle, Yvonne Böttcher, Heather A. Boyd, Marcel Bruinenberg, Ida H. Caspersen, Yii-Der Ida Chen, Robert Clarke, E. Warwick Daw, Anton J. M. de Craen, Graciela Delgado, Maria Dimitriou, Alex S. F. Doney, Niina Eklund, Karol Estrada, Elodie Eury, Lasse Folkersen, Ross M. Fraser, Melissa E. Garcia, Frank Geller, Vilmantas Giedraitis, Bruna Gigante, Alan S. Go, Alain Golay, Alison H. Goodall, Scott D. Gordon, Mathias Gorski, Hans-Jörgen Grabe, Harald Grallert, Tanja B. Grammer, Jürgen Gräßler, Henrik Grönberg, Christopher J. Groves, Gaëlle Gusto, Jeffrey Haessler, Per Hall, Toomas Haller, Goran Hallmans, Catharina A. Hartman, Maija Hassinen, Caroline Hayward, Nancy L. Heard-Costa, Quinta Helmer, Christian Hengstenberg, Oddgeir Holmen, Jouke-Jan Hottenga, Alan L. James, Janina M. Jeff, Åsa Johansson, Jennifer Jolley, Thorhildur Juliusdottir, Leena Kinnunen, Wolfgang Koenig, Markku Koskenvuo, Wolfgang Kratzer, Jaana Laitinen, Claudia Lamina, Karin Leander, Nanette R. Lee, Peter Lichtner, Lars Lind, Jaana Lindström, Ken Sin Lo, Stéphane Lobbens, Roberto Lorbeer, Yingchang Lu, François Mach, Patrik K. E. Magnusson, Anubha Mahajan, Wendy L. McArdle, Stela McLachlan, Cristina Menni, Sigrun Merger, Evelin Mihailov, Lili Milani, Alireza Moayyeri, Keri L. Monda, Mario A. Morken, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Arthur W. Musk, Ramaiah Nagaraja, Markus M. Nöthen, Ilja M. Nolte, Stefan Pilz, Nigel W. Rayner, Frida Renstrom, Rainer Rettig, Janina S. Ried, Stephan Ripke, Neil R. Robertson, Lynda M. Rose, Serena Sanna, Hubert Scharnagl, Salome Scholtens, Fredrick R. Schumacher, William R. Scott, Thomas Seufferlein, Jianxin Shi, Albert Vernon Smith, Joanna Smolonska, Alice V. Stanton, Valgerdur Steinthorsdottir, Kathleen Stirrups, Heather M. Stringham, Johan Sundström, Morris A. Swertz, Amy J. Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Bamidele O. Tayo, Barbara Thorand, Gudmar Thorleifsson, Jonathan P. Tyrer, Hae-Won Uh, Liesbeth Vandenput, Frank C. Verhulst, Sita H. Vermeulen, Niek Verweij, Judith M. Vonk, Lindsay L. Waite, Helen R. Warren, Dawn Waterworth, Michael N. Weedon, Lynne R. Wilkens, Christina Willenborg, Tom Wilsgaard, Mary K. Wojczynski, Andrew Wong, Alan F. Wright, Qunyuan Zhang, The LifeLines Cohort Study, Eoin P. Brennan, Murim Choi, Zari Dastani, Alexander W. Drong, Per Eriksson, Anders Franco-Cereceda, Jesper R. Gådin, Ali G. Gharavi, Michael E. Goddard, Robert E. Handsaker, Jinyan Huang, Fredrik Karpe, Sekar Kathiresan, Sarah Keildson, Krzysztof Kiryluk, Michiaki Kubo, Jong-Young Lee, Liming Liang, Richard P. Lifton, Baoshan Ma, Steven A. McCarroll, Amy J. McKnight, Josine L. Min, Miriam F. Moffatt, Grant W. Montgomery, Joanne M. Murabito, George Nicholson, Dale R. Nyholt, Yukinori Okada, John R. B. Perry, Rajkumar Dorajoo, Eva Reinmaa, Rany M. Salem, Niina Sandholm, Robert A. Scott, Lisette Stolk, Atsushi Takahashi, Toshihiro Tanaka, Ferdinand M. van’t Hooft, Anna A. E. Vinkhuyzen, Harm-Jan Westra, Wei Zheng, Krina T. Zondervan, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CAIOGRAMplusC4D Consortium, The CKDGen Consortium, GLGC The, ICBP The, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium, Andrew C. Heath, Dominique Arveiler, Stephan J. L. Bakker, John Beilby, Richard N. Bergman, John Blangero, Pascal Bovet, Harry Campbell, Mark J. Caulfield, Giancarlo Cesana, Aravinda Chakravarti, Daniel I. Chasman, Peter S. Chines, Francis S. Collins, Dana C. Crawford, L. Adrienne Cupples, Daniele Cusi, John Danesh, Ulf de Faire, Hester M. den Ruijter, Anna F. Dominiczak, Raimund Erbel, Jeanette Erdmann, Johan G. Eriksson, Martin Farrall, Stephan B. Felix, Ele Ferrannini, Jean Ferrières, Ian Ford, Nita G. Forouhi, Terrence Forrester, Oscar H. Franco, Ron T. Gansevoort, Pablo V. Gejman, Christian Gieger, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, Alistair S. Hall, Tamara B. Harris, Andrew T. Hattersley, Andrew A. Hicks, Lucia A. Hindorff, Aroon D. Hingorani, Albert Hofman, Georg Homuth, G. Kees Hovingh, Steve E. Humphries, Steven C. Hunt, Elina Hyppönen, Thomas Illig, Kevin B. Jacobs, Marjo-Riitta Jarvelin, Karl-Heinz Jöckel, Berit Johansen, Pekka Jousilahti, J. Wouter Jukema, Antti M. Jula, Jaakko Kaprio, John J. P. Kastelein, Sirkka M. Keinanen-Kiukaanniemi, Lambertus A. Kiemeney, Paul Knekt, Jaspal S. Kooner, Charles Kooperberg, Peter Kovacs, Aldi T. Kraja, Meena Kumari, Johanna Kuusisto, Timo A. Lakka, Claudia Langenberg, Loic Le Marchand, Terho Lehtimäki, Valeriya Lyssenko, Satu Männistö, André Marette, Tara C. Matise, Colin A. McKenzie, Barbara McKnight, Frans L. Moll, Andrew D. Morris, Andrew P. Morris, Jeffrey C. Murray, Mari Nelis, Claes Ohlsson, Albertine J. Oldehinkel, Ken K. Ong, Pamela A. F. Madden, Gerard Pasterkamp, John F. Peden, Annette Peters, Dirkje S. Postma, Peter P. Pramstaller, Jackie F. Price, Lu Qi, Olli T. Raitakari, Tuomo Rankinen, D. C. Rao, Treva K. Rice, Paul M. Ridker, John D. Rioux, Marylyn D. Ritchie, Igor Rudan, Veikko Salomaa, Nilesh J. Samani, Jouko Saramies, Mark A. Sarzynski, Heribert Schunkert, Peter E. H. Schwarz, Peter Sever, Alan R. Shuldiner, Juha Sinisalo, Ronald P. Stolk, Konstantin Strauch, Anke Tönjes, David-Alexandre Trégouët, Angelo Tremblay, Elena Tremoli, Jarmo Virtamo, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Gonneke Willemsen, Jacqueline C. Witteman, M. Carola Zillikens, Linda S. Adair, Philippe Amouyel, Folkert W. Asselbergs, Themistocles L. Assimes, Murielle Bochud, Bernhard O. Boehm, Eric Boerwinkle, Stefan R. Bornstein, Erwin P. Bottinger, Claude Bouchard, Stéphane Cauchi, John C. Chambers, Stephen J. Chanock, Richard S. Cooper, Paul I. W. de Bakker, George Dedoussis, Luigi Ferrucci, Paul W. Franks, Philippe Froguel, Leif C. Groop, Christopher A. Haiman, Anders Hamsten, Jennie Hui, David J. Hunter, Kristian Hveem, Robert C. Kaplan, Mika Kivimaki, Diana Kuh, Markku Laakso, Yongmei Liu, Nicholas G. Martin, Winfried März, Mads Melbye, Andres Metspalu, Susanne Moebus, Patricia B. Munroe, Inger Njølstad, Ben A. Oostra, Colin N. A. Palmer, Nancy L. Pedersen, Markus Perola, Louis Pérusse, Ulrike Peters, Chris Power, Thomas Quertermous, Rainer Rauramaa, Fernando Rivadeneira, Timo E. Saaristo, Danish Saleheen, Naveed Sattar, Eric E. Schadt, David Schlessinger, P. Eline Slagboom, Harold Snieder, Tim D. Spector, Unnur Thorsteinsdottir, Michael Stumvoll, Jaakko Tuomilehto, André G. Uitterlinden, Matti Uusitupa, Pim van der Harst, Mark Walker, Henri Wallaschofski, Nicholas J. Wareham, Hugh Watkins, David R. Weir, H-Erich Wichmann, James F. Wilson, Pieter Zanen, Ingrid B. Borecki, Panos Deloukas, Caroline S. Fox, Iris M. Heid, Jeffrey R. O’Connell, David P. Strachan, Kari Stefansson, Cornelia M. van Duijn, Gonçalo R. Abecasis, Lude Franke, Timothy M. Frayling, Mark I. McCarthy, Peter M. Visscher, André Scherag, Cristen J. Willer, Michael Boehnke, Karen L. Mohlke, Cecilia M. Lindgren, Jacques S. Beckmann, Inês Barroso, Kari E. North, Erik Ingelsson, Joel N. Hirschhorn, Ruth J. F. Loos, Elizabeth K. Speliotes

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. More... »

PAGES

197

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  • Journal

    TITLE

    Nature

    ISSUE

    7538

    VOLUME

    518

    Author Affiliations

  • University of Michigan–Ann Arbor
  • National Institutes of Health
  • University of North Carolina at Chapel Hill
  • Technical University of Denmark
  • Institute of Metabolic Science
  • Broad Institute
  • University of Queensland
  • Brigham and Women's Hospital
  • University of Tartu
  • Uppsala University
  • Wellcome Centre for Human Genetics
  • University of Lausanne
  • Wellcome Sanger Institute
  • University of Regensburg
  • University of Exeter
  • Harvard University
  • HudsonAlpha Institute for Biotechnology
  • Erasmus University Medical Center
  • University of Western Australia
  • Leiden University Medical Center
  • University of Edinburgh
  • Rutgers University
  • Imperial College London
  • University Hospital of Geneva
  • Statens Serum Institut
  • Washington University in St. Louis
  • University of Oxford
  • Fred Hutchinson Cancer Research Center
  • Queen Mary University of London
  • University Hospital Ulm
  • National Institute for Health and Welfare
  • University of Hawaii at Manoa
  • Icahn School of Medicine at Mount Sinai
  • King's College London
  • QIMR Berghofer Medical Research Institute
  • Essen University Hospital
  • Umeå University
  • University of Eastern Finland
  • Karolinska Institute
  • National Institute on Aging
  • University of Greifswald
  • University Medical Center Utrecht
  • University Medical Center Groningen
  • Leidos (United States)
  • Université Lille 2 Droit et Santé
  • Helmholtz Zentrum München
  • Dalarna University
  • Pathwest Laboratory Medicine
  • NHS Blood and Transplant
  • Azienda Sanitaria di Firenze
  • University of San Carlos
  • Queensland University of Technology
  • Leipzig University
  • National Human Genome Research Institute
  • Norwegian University of Science and Technology
  • University of California Los Angeles
  • Heidelberg University
  • Harokopio University
  • University of Helsinki
  • Massachusetts General Hospital
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • Kaiser Permanente
  • Glenfield Hospital
  • University Hospital Regensburg
  • German Center for Neurodegenerative Diseases
  • German Center for Diabetes Research
  • UC-Institut inter Régional pour la SAnté
  • Kuopion Liikuntalääketieteen Tutkimuslaitos
  • Boston University School of Medicine
  • VU University Amsterdam
  • Technical University Munich
  • University of Ulm
  • Finnish Institute of Occupational Health
  • Innsbruck Medical University
  • Montreal Heart Institute
  • University of Bristol
  • University College London
  • Amgen (United States)
  • Institute of Genetic and Biomedical Research
  • Ludwig Maximilian University of Munich
  • Sir Charles Gairdner Hospital
  • University of Bonn
  • Medical University of Graz
  • Lund University
  • University of Southern California
  • National Cancer Institute
  • University of Iceland
  • Royal College of Surgeons in Ireland
  • deCODE Genetics (Iceland)
  • Loyola University Chicago
  • University of Cambridge
  • University of Gothenburg
  • Radboud University Nijmegen Medical Centre
  • GlaxoSmithKline (United States)
  • University of Lübeck
  • The Arctic University of Norway
  • MRC Unit for Lifelong Health and Ageing
  • University College Dublin
  • Seoul National University
  • Columbia University
  • University of Melbourne
  • Shanghai Institute of Hematology
  • NIHR Oxford Musculoskeletal Biomedical Research Unit
  • RIKEN
  • Korea National Institute of Health
  • Yale University
  • Dalian Maritime University
  • Queen's University Belfast
  • Medical Research Council Harwell
  • Tokyo Medical and Dental University
  • Genome Institute of Singapore
  • Vanderbilt University Medical Center
  • University of Strasbourg
  • Texas Biomedical Research Institute
  • Ministry of Health
  • University of Milan
  • Johns Hopkins University
  • Vanderbilt University
  • Boston University
  • Fondazione Filarete
  • University of Glasgow
  • Helsinki University Central Hospital
  • German Centre for Cardiovascular Research
  • University of Pisa
  • Hôpital Rangueil
  • University of the West Indies
  • NorthShore University HealthSystem
  • University of Leeds
  • European Academy of Bozen
  • Academic Medical Center
  • University of Utah
  • Hannover Medical School
  • University of Oulu
  • Netherlands Heart Institute
  • Oulu University Hospital
  • Imperial College Healthcare NHS Trust
  • University of Essex
  • University of Tampere
  • Université Laval
  • University of Washington
  • University of Liverpool
  • University of Iowa
  • Illumina (United Kingdom)
  • Ospedale di Bolzano
  • University of Turku
  • Pennington Biomedical Research Center
  • University of Montreal
  • Pennsylvania State University
  • University of Split
  • South Karelia Central Hospital
  • Baltimore VA Medical Center
  • Institute of Cardiometabolism And Nutrition
  • University of North Carolina System
  • Stanford University
  • The University of Texas Health Science Center at Houston
  • Albert Einstein College of Medicine
  • Wake Forest University
  • Synlab (Germany)
  • University of Copenhagen
  • Pirkanmaa Hospital District
  • University of Pennsylvania
  • Danube University Krems
  • Kuopio University Hospital
  • Newcastle University
  • King Abdulaziz University
  • National Heart Lung and Blood Institute
  • University of Maryland, Baltimore
  • Jena University Hospital
  • University Hospital of Lausanne
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature14177

    DOI

    http://dx.doi.org/10.1038/nature14177

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1053003561

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25673413


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