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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

  • Sonja I. Berndt
  • , Stefan Gustafsson
  • , Reedik Mägi
  • , Andrea Ganna
  • , Eleanor Wheeler
  • , Mary F. Feitosa
  • , Anne E. Justice
  • , Keri L. Monda
  • , Damien C. Croteau-Chonka
  • , Felix R. Day
  • , Tõnu Esko
  • , Tove Fall
  • , Teresa Ferreira
  • , Davide Gentilini
  • , Anne U. Jackson
  • , Jianan Luan
  • , Joshua C. Randall
  • , Sailaja Vedantam
  • , Cristen J. Willer
  • , Thomas W. Winkler
  • Andrew R. Wood, Tsegaselassie Workalemahu, Yi Juan Hu, Sang Hong Lee, Liming Liang, Dan Yu Lin, Josine L. Min, Benjamin M. Neale, Gudmar Thorleifsson, Jian Yang, Eva Albrecht, Najaf Amin, Jennifer L. Bragg-Gresham, Gemma Cadby, Martin Den Heijer, Niina Eklund, Krista Fischer, Anuj Goel, Jouke Jan Hottenga, Jennifer E. Huffman, Ivonne Jarick, Åsa Johansson, Toby Johnson, Stavroula Kanoni, Marcus E. Kleber, Inke R. König, Kati Kristiansson, Zoltán Kutalik, Claudia Lamina, Cecile Lecoeur, Guo Li, Massimo Mangino, Wendy L. McArdle, Carolina Medina-Gomez, Martina Müller-Nurasyid, Julius S. Ngwa, Ilja M. Nolte, Lavinia Paternoster, Sonali Pechlivanis, Markus Perola, Marjolein J. Peters, Michael Preuss, Lynda M. Rose, Jianxin Shi, Dmitry Shungin, Albert Vernon Smith, Rona J. Strawbridge, Ida Surakka, Alexander Teumer, Mieke D. Trip, Jonathan Tyrer, Jana V. Van Vliet-Ostaptchouk, Liesbeth Vandenput, Lindsay L. Waite, Jing Hua Zhao, Devin Absher, Folkert W. Asselbergs, Mustafa Atalay, Antony P. Attwood, Anthony J. Balmforth, Hanneke Basart, John Beilby, Lori L. Bonnycastle, Paolo Brambilla, Marcel Bruinenberg, Harry Campbell, Daniel I. Chasman, Peter S. Chines, Francis S. Collins, John M. Connell, William O Cookson, Ulf De Faire, Femmie De Vegt, Mariano Dei, Maria Dimitriou, Sarah Edkins, Karol Estrada, David M. Evans, Martin Farrall, Marco M. Ferrario, Jean Ferrières, Lude Franke, Francesca Frau, Pablo V. Gejman, Harald Grallert, Henrik Grönberg, Vilmundur Gudnason, Alistair S. Hall, Per Hall, Anna Liisa Hartikainen, Caroline Hayward, Nancy L. Heard-Costa, Andrew C. Heath, Johannes Hebebrand, Georg Homuth, Frank B. Hu, Sarah E. Hunt, Elina Hyppönen, Carlos Iribarren, Kevin B. Jacobs, John Olov Jansson, Antti Jula, Mika Kähönen, Sekar Kathiresan, Frank Kee, Kay Tee Khaw, Mika Kivimäki, Wolfgang Koenig, Aldi T. Kraja, Meena Kumari, Kari Kuulasmaa, Johanna Kuusisto, Jaana H. Laitinen, Timo A. Lakka, Claudia Langenberg, Lenore J. Launer, Lars Lind, Jaana Lindström, Jianjun Liu, Antonio Liuzzi, Marja Liisa Lokki, Mattias Lorentzon, Pamela A. Madden, Patrik K. Magnusson, Paolo Manunta, Diana Marek, Winfried März, Irene Mateo Leach, Barbara McKnight, Sarah E. Medland, Evelin Mihailov, Lili Milani, Grant W. Montgomery, Vincent Mooser, Thomas W. Mühleisen, Patricia B. Munroe, Arthur W. Musk, Narisu Narisu, Gerjan Navis, George Nicholson, Ellen A. Nohr, Ken K. Ong, Ben A. Oostra, Colin N. Palmer, Aarno Palotie, John F. Peden, Nancy Pedersen, Annette Peters, Ozren Polasek, Anneli Pouta, Peter P. Pramstaller, Inga Prokopenko, Carolin Pütter, Aparna Radhakrishnan, Olli Raitakari, Augusto Rendon, Fernando Rivadeneira, Igor Rudan, Timo E. Saaristo, Jennifer G. Sambrook, Alan R. Sanders, Serena Sanna, Jouko Saramies, Sabine Schipf, Stefan Schreiber, Heribert Schunkert, So Youn Shin, Stefano Signorini, Juha Sinisalo, Boris Skrobek, Nicole Soranzo, Alena Stancáková, Klaus Stark, Jonathan C. Stephens, Kathleen Stirrups, Ronald P. Stolk, Michael Stumvoll, Amy J. Swift, Eirini V. Theodoraki, Barbara Thorand, David Alexandre Tregouet, Elena Tremoli, Melanie M. Van Der Klauw, Joyce B. Van Meurs, Sita H. Vermeulen, Jorma Viikari, Jarmo Virtamo, Veronique Vitart, Gérard Waeber, Zhaoming Wang, Elisabeth Widén, Sarah H. Wild, Gonneke Willemsen, Bernhard R. Winkelmann, Jacqueline C. Witteman, Bruce H. Wolffenbuttel, Andrew Wong, Alan F. Wright, M. Carola Zillikens, Philippe Amouyel, Bernhard O. Boehm, Eric Boerwinkle, Dorret I. Boomsma, Mark J. Caulfield, Stephen J. Chanock, L. Adrienne Cupples, Daniele Cusi, George V. Dedoussis, Jeanette Erdmann, Johan G. Eriksson, Paul W. Franks, Philippe Froguel, Christian Gieger, Ulf Gyllensten, Anders Hamsten, Tamara B. Harris, Christian Hengstenberg, Andrew A. Hicks, Aroon Hingorani, Anke Hinney, Albert Hofman, Kees G. Hovingh, Kristian Hveem, Thomas Illig, Marjo Riitta Jarvelin, Karl Heinz Jöckel, Sirkka M. Keinanen-Kiukaanniemi, Lambertus A. Kiemeney, Diana Kuh, Markku Laakso, Terho Lehtimäki, Douglas F. Levinson, Nicholas G. Martin, Andres Metspalu, Andrew D. Morris, Markku S. Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J. Oldehinkel, Willem H. Ouwehand, Lyle J. Palmer, Brenda Penninx, Chris Power, Michael A. Province, Bruce M. Psaty, Lu Qi, Rainer Rauramaa, Paul M. Ridker, Samuli Ripatti, Veikko Salomaa, Nilesh J. Samani, Harold Snieder, Thorkild I. Sørensen, Timothy D. Spector, Kari Stefansson, Anke Tönjes, Jaakko Tuomilehto, André G. Uitterlinden, Matti Uusitupa, Pim Van Der Harst, Peter Vollenweider, Henri Wallaschofski, Nicholas J. Wareham, Hugh Watkins, H. Erich Wichmann, James F. Wilson, Goncalo R. Abecasis, Themistocles L. Assimes, Inês Barroso, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Caroline S. Fox, Timothy Frayling, Leif C. Groop, Talin Haritunian, Iris M. Heid, David Hunter, Robert C. Kaplan, Fredrik Karpe, Miriam F. Moffatt, Karen L. Mohlke, Jeffrey R. O'Connell, Yudi Pawitan, Eric E. Schadt, David Schlessinger, Valgerdur Steinthorsdottir, David P. Strachan, Unnur Thorsteinsdottir, Cornelia M. Van Duijn, Peter M. Visscher, Anna Maria Di Blasio, Joel N. Hirschhorn, Cecilia M. Lindgren, Andrew P. Morris, David Meyre, André Scherag, Mark I. McCarthy, Elizabeth K. Speliotes, Kari E. North, Ruth J. Loos, Erik Ingelsson*
*Corresponding author for this work
  • National Institutes of Health
  • Uppsala University
  • Karolinska Institutet
  • University of Oxford
  • University of Tartu
  • Wellcome Trust Sanger Institute
  • Washington University St. Louis
  • University of North Carolina at Chapel Hill
  • Amgen Incorporated
  • Cambridge University Hospitals NHS Foundation Trust
  • University of Tartu
  • IRCCS Istituto Auxologico Italiano - Milano
  • University of Michigan, Ann Arbor
  • Boston Children's Hospital
  • Broad Institute
  • Harvard University
  • University of Regensburg
  • University of Exeter
  • Brigham and Women’s Hospital
  • Emory University
  • University of Queensland
  • Massachusetts General Hospital
  • deCODE Genetics
  • Queensland Institute of Medical Research
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • Erasmus University Rotterdam
  • Ontario Institute for Cancer Research
  • University of Toronto
  • University of Western Australia
  • VU University Medical Center
  • National Institute for Health and Welfare
  • Vrije Universiteit Amsterdam
  • NHS Lothian
  • University of Marburg
  • Queen Mary University of London
  • Ludwigshafen Risk and Cardiovascular Health (LURIC) Study
  • Heidelberg University 
  • University of Lübeck
  • University of Lausanne
  • Swiss Institute of Bioinformatics
  • Innsbruck Medical University
  • Université de Lille
  • CNRS
  • University of Washington
  • King's College London
  • University of Bristol
  • Netherlands Genomics Initiative
  • Ludwig Maximilian University of Munich
  • Boston University
  • University of Groningen
  • University of Duisburg-Essen
  • University of Helsinki
  • Lund University
  • Umeå University
  • Icelandic Heart Association
  • University of Iceland
  • University of Greifswald
  • Amsterdam University Medical Centers
  • University of Cambridge
  • University of Gothenburg
  • HudsonAlpha Institute for Biotechnology
  • Utrecht University
  • University of Eastern Finland
  • National Institute for Health and Care Research
  • University of Leeds
  • Queen Elizabeth II Medical Centre Trust
  • University of Milan - Bicocca
  • University of Edinburgh
  • University of Glasgow
  • University of Dundee
  • Imperial College London
  • Radboud University Nijmegen
  • National Research Council of Italy
  • Harokopio University
  • University of Insubria
  • INSERM UMR 1043 and Paul Sabatier University
  • University of Milan
  • The University of Chicago
  • NorthShore University HealthSystem
  • University of Oulu
  • University College London
  • Kaiser Permanente
  • SAIC
  • Tampere University
  • Queen's University Belfast
  • Ulm University
  • Finnish Institute of Occupational Health
  • Agency for Science, Technology and Research, Singapore
  • Vita-Salute San Raffaele University
  • SYNLAB International GmbH
  • GlaxoSmithKline
  • University of Bonn
  • Sir Charles Gairdner Hospital
  • MRC Harwell Institute
  • Aarhus University
  • Medical Research Council
  • Leiden University
  • Illumina, Inc.
  • Munich Heart Alliance
  • University of Split
  • EURAC Research
  • General Central Hospital
  • NHS Blood and Transplant
  • University of Turku
  • Finnish Diabetes Association
  • Pirkanmaa Hospital District
  • South Karelia Central Hospital
  • Kiel University
  • German Centre for Cardiovascular Research
  • Azienda Ospedaliera di Desio e Vimercate
  • Helsinki University Hospital
  • Klinik und Poliklinik für Innere Medizin II
  • Leipzig University
  • Institut national de la santé et de la recherche médicale
  • Cardiology Group
  • University of Texas Health Science Center at Houston
  • Fondazione Filarete
  • Norwegian University of Science and Technology
  • Hannover Medical School
  • Netherlands Association of Comprehensive Cancer Centres
  • Stanford University
  • University of Tromsø – The Arctic University of Norway
  • Group Health Cooperative
  • University of Leicester
  • University Hospitals of Leicester NHS Trust
  • University of Copenhagen
  • University for Continuing Education Krems
  • King Abdulaziz University
  • National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
  • Cedars-Sinai Medical Center
  • Albert Einstein College of Medicine
  • Oxford University Hospitals NHS Foundation Trust
  • University of Maryland, Baltimore
  • Icahn School of Medicine at Mount Sinai
  • St. George’s Hospital
  • McMaster University

Research output: Contribution to journalArticlepeer-review

Abstract

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Original languageEnglish
Pages (from-to)501-512
Number of pages12
JournalNature Genetics
Volume45
Issue number5
DOIs
Publication statusPublished - May 2013
Externally publishedYes

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