Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

Cecilia M. Lindgren; Iris M. Heid; Joshua C. Randall; Claudia Lamina; Valgerdur Steinthorsdottir; Lu Qi; Elizabeth K. Speliotes; Gudmar Thorleifsson; Cristen J. Willer; Blanca M. Herrera; Anne U. Jackson; Noha Lim; Paul Scheet; Nicole Soranzo; Najaf Amin; Yurii S. Aulchenko; John C. Chambers; Alexander Drong; Jian'an Luan; Helen N. Lyon; Fernando Rivadeneira; Serena Sanna; Nicholas J. Timpson; M. Carola Zillikens; Jing Hua Zhao; Peter Almgren; Stefania Bandinelli; Amanda J. Bennett; Richard N. Bergman; Lori L. Bonnycastle; Suzannah J. Bumpstead; Stephen J. Chanock; Lynn Cherkas; Peter Chines; Lachlan Coin; Cyrus Cooper; Gabriel Crawford; Angela Doering; Anna Dominiczak; Alex S. F. Doney; Shah Ebrahim; Paul Elliott; Michael R. Erdos; Karol Estrada; Luigi Ferrucci; Guido Fischer; Nita G. Forouhi; Christian Gieger; Harald Grallert; Christopher J. Groves; Scott Grundy; Candace Guiducci; David Hadley; Anders Hamsten; Aki S. Havulinna; Albert Hofman; Rolf Holle; John W. Holloway; Thomas Illig; Bo Isomaa; Leonie C. Jacobs; Karen Jameson; Pekka Jousilahti; Fredrik Karpe; Johanna Kuusisto; Jaana Laitinen; G. Mark Lathrop; Debbie A. Lawlor; Massimo Mangino; Wendy L. McArdle; Thomas Meitinger; Mario A. Morken; Andrew P. Morris; Patricia Munroe; Narisu Narisu; Anna Nordstrom; Peter Nordstroem; Ben A. Oostra; Colin N. A. Palmer; Felicity Payne; John F. Peden; Inga Prokopenko; Frida Renstroem; Aimo Ruokonen; Veikko Salomaa; Manjinder S. Sandhu; Laura J. Scott; Angelo Scuteri; Kaisa Silander; Kijoung Song; Xin Yuan; Heather M. Stringham; Amy J. Swift; Tiinamaija Tuomi; Manuela Uda; Peter Vollenweider; Gerard Waeber; Chris Wallace; G. Bragi Walters; Michael N. Weedon; Jacqueline C. M. Witteman; Cuilin Zhang; Weihua Zhang; Mark J. Caulfield; Francis S. Collins; George Davey Smith; Ian N. M. Day; Paul W. Franks; Andrew T. Hattersley; Frank B. Hu; Marjo-Riitta Jarvelin; Augustine Kong; Jaspal S. Kooner; Markku Laakso; Edward Lakatta; Vincent Mooser; Andrew D. Morris; Leena Peltonen; Nilesh J. Samani; Timothy D. Spector; David P. Strachan; Toshiko Tanaka; Jaakko Tuomilehto; Andre G. Uitterlinden; Cornelia M. van Duijn; Nicholas J. Wareham; Hugh Watkins; Dawn M. Waterworth; Michael Boehnke; Panos Deloukas; Leif Groop; David J. Hunter; Unnur Thorsteinsdottir; David Schlessinger; H. -Erich Wichmann; Timothy M. Frayling; Goncalo R. Abecasis; Joel N. Hirschhorn; Ruth J. F. Loos; Kari Stefansson; Karen L. Mohlke; Ine S. Barroso; Mark I. McCarthy; Wellcome Trust Case Control Consor

doi:10.1371/journal.pgen.1000508

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Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

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Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

Cecilia M. Lindgren, Iris M. Heid, Joshua C. Randall, Claudia Lamina, Valgerdur Steinthorsdottir, Lu Qi, Elizabeth K. Speliotes, Gudmar Thorleifsson, Cristen J. Willer, Blanca M. Herrera, …

PLoS genetics, Vol.5(6), pp.e1000508-e1000508

01/06/2009

DOI: https://doi.org/10.1371/journal.pgen.1000508

PMID: 19557161

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

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Title: Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution
Creators - without role: Cecilia M. Lindgren - University of Oxford
Iris M. Heid - Helmholtz Zentrum München
Joshua C. Randall - University of Oxford
Claudia Lamina - Helmholtz Zentrum München
Valgerdur Steinthorsdottir - deCODE Genet, Reykjavik, Iceland
Lu Qi - Harvard University
Elizabeth K. Speliotes - Harvard University
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Cristen J. Willer - Biostat
Blanca M. Herrera - University of Oxford
Anne U. Jackson - Biostat
Noha Lim - College Station Medical Center
Paul Scheet - Biostat
Nicole Soranzo - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Najaf Amin - Erasmus MC
Yurii S. Aulchenko - Erasmus MC
John C. Chambers - University of London
Alexander Drong - University of Oxford
Jian'an Luan - Massachusetts Rehabilitation Commission
Helen N. Lyon - Broad Institute
Fernando Rivadeneira - Erasmus MC
Serena Sanna - CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy
Nicholas J. Timpson - University of Bristol
M. Carola Zillikens - Erasmus MC
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Peter Almgren - Malmö University
Stefania Bandinelli - Florence
Amanda J. Bennett - University of Oxford
Richard N. Bergman - Supreme Council Of Health
Lori L. Bonnycastle - NHGRI, Bethesda, MD 20892 USA
Suzannah J. Bumpstead - Wellcome Sanger Institute
Stephen J. Chanock - NCI, Radiat Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA
Lynn Cherkas - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Peter Chines - NHGRI, Bethesda, MD 20892 USA
Lachlan Coin - University of London
Cyrus Cooper - University of Southampton
Gabriel Crawford - Broad Institute
Angela Doering - Helmholtz Zentrum München
Anna Dominiczak - University of Glasgow
Alex S. F. Doney - University of Dundee
Shah Ebrahim - University of Bristol
Paul Elliott - University of London
Michael R. Erdos - NHGRI, Bethesda, MD 20892 USA
Karol Estrada - Erasmus MC
Luigi Ferrucci - NIA, Clin Res Branch, Baltimore, MD 21224 USA
Guido Fischer - Helmholtz Zentrum München
Nita G. Forouhi
Christian Gieger - Helmholtz Zentrum München
Harald Grallert - Helmholtz Zentrum München
Christopher J. Groves - University of Oxford
Scott Grundy - College Station Medical Center
Candace Guiducci - Broad Institute
David Hadley - University of London
Anders Hamsten - Karolinska Institutet
Aki S. Havulinna - KTL Natl Publ Hlth Inst, Helsinki, Finland
Albert Hofman - Erasmus MC
Rolf Holle - Helmholtz Zentrum München
John W. Holloway - University of Southampton
Thomas Illig
Bo Isomaa - Malmska Municipal Hlth Ctr & Hosp, Folkhalsan Res Ctr, Pietarsaari, Finland
Leonie C. Jacobs - Erasmus MC
Karen Jameson - University of Southampton
Pekka Jousilahti - KTL Natl Publ Hlth Inst, Helsinki, Finland
Fredrik Karpe - University of Oxford
Johanna Kuusisto - University of Helsinki
Jaana Laitinen - Finnish Inst Occpat Hlth, Oulu, Finland
G. Mark Lathrop - Evry
Debbie A. Lawlor - University of Bristol
Massimo Mangino - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Wendy L. McArdle - University of Bristol
Thomas Meitinger - Helmholtz Zentrum München
Mario A. Morken - NHGRI, Bethesda, MD 20892 USA
Andrew P. Morris - University of Oxford
Patricia Munroe - Queen Mary University of London
Narisu Narisu - NHGRI, Bethesda, MD 20892 USA
Anna Nordstrom - Umeå University
Peter Nordstroem - Umeå University
Ben A. Oostra - Erasmus MC
Colin N. A. Palmer - University of Dundee
Felicity Payne - Wellcome Sanger Institute
John F. Peden - University of Oxford
Inga Prokopenko - University of Oxford
Frida Renstroem - Umeå University
Aimo Ruokonen - University of Oulu
Veikko Salomaa - KTL Natl Publ Hlth Inst, Helsinki, Finland
Manjinder S. Sandhu - Massachusetts Rehabilitation Commission
Laura J. Scott - Biostat
Angelo Scuteri - Istituto Nazionale di Riposo e Cura per Anziani
Kaisa Silander - College Station Medical Center
Kijoung Song - College Station Medical Center
Xin Yuan - College Station Medical Center
Heather M. Stringham - Biostat
Amy J. Swift - NHGRI, Bethesda, MD 20892 USA
Tiinamaija Tuomi - University of Helsinki
Manuela Uda - CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy
Peter Vollenweider
Gerard Waeber - College Station Medical Center
Chris Wallace - Queen Mary University of London
G. Bragi Walters - deCODE Genet, Reykjavik, Iceland
Michael N. Weedon - Supreme Council Of Health
Jacqueline C. M. Witteman - Erasmus MC
Cuilin Zhang - NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA
Weihua Zhang - Ealing Gen Hosp, Natl Hlth Serv Trust, Southall, Middx, England
Mark J. Caulfield - Queen Mary University of London
Francis S. Collins - NHGRI, Bethesda, MD 20892 USA
George Davey Smith - University of Bristol
Ian N. M. Day - University of Bristol
Paul W. Franks - Umeå University
Andrew T. Hattersley - Supreme Council Of Health
Frank B. Hu - Harvard University
Marjo-Riitta Jarvelin - University of London
Augustine Kong - deCODE Genet, Reykjavik, Iceland
Jaspal S. Kooner - University of London
Markku Laakso - University of Helsinki
Edward Lakatta - NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA
Vincent Mooser - College Station Medical Center
Andrew D. Morris - University of Dundee
Leena Peltonen - Wellcome Sanger Institute
Nilesh J. Samani - University of Leicester
Timothy D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
David P. Strachan - University of London
Toshiko Tanaka - NIA, Clin Res Branch, Baltimore, MD 21224 USA
Jaakko Tuomilehto - Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet Unit, Helsinki, Finland
Andre G. Uitterlinden - Erasmus MC
Cornelia M. van Duijn - Erasmus MC
Nicholas J. Wareham - Massachusetts Rehabilitation Commission
Hugh Watkins - University of Oxford
Dawn M. Waterworth - College Station Medical Center
Michael Boehnke - Biostat
Panos Deloukas - Addenbrookes Hosp, Inst Metab Sci, Cambridge, England
Leif Groop - Malmö University
David J. Hunter - Harvard University
Unnur Thorsteinsdottir - deCODE Genet, Reykjavik, Iceland
David Schlessinger - NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA
H. -Erich Wichmann - Helmholtz Zentrum München
Timothy M. Frayling - Supreme Council Of Health
Goncalo R. Abecasis - Biostat
Joel N. Hirschhorn - Broad Institute
Ruth J. F. Loos - Massachusetts Rehabilitation Commission
Kari Stefansson - deCODE Genet, Reykjavik, Iceland
Karen L. Mohlke - Univ N Carolina, Dept Genet, Chapel Hill, NC USA
Ine S. Barroso - Wellcome Sanger Institute
Mark I. McCarthy - University of Oxford
Wellcome Trust Case Control Consor
Publication Details: PLoS genetics, Vol.5(6), pp.e1000508-e1000508
Publisher: Public Library Science
Number of pages: 13
Grant note: G0601261; G0701863; G0600705; MC_qA137934; G0000934; G9521010; G0801056; MC_U106188470 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G0601261; G9521010; MC_U106188470; MC_qA137934; G0801056; G0000934; G0801056B; G0701863; G0600705; U1475000001; G0600717B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) DK062370; DK072193; DK075787; DK079466; DK080145; DK067288; DK07191 / NIDDK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Netherlands Organization for Scientific Research; Netherlands Organization for Scientific Research (NWO) Faculty of Biology and Medicine of Lausanne, Switzerland ADA Smith Family Foundation Pinnacle Program German National Genome Research Net, GlaxoSmithKline; GlaxoSmithKline UK Department of Health Policy Research Programme 33CSCO-122661 / Swiss National Science Foundation; Swiss National Science Foundation (SNSF) HL087679; HL084729 / NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) The Barts Netherlands Center of Medical Systems Biology N01-HG-65403 / The London Charity, Biocentrum Helsinki, Biotechnology and Biological Sciences Research Council (UK), British Heart Foundation, Camstrad, Cancer Research UK, CIDR; British Heart Foundation; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Cancer Research UK UK National Institute of Health Research; National Institutes of Health Research (NIHR) 104781; 124243 / Academy of Finland; Research Council of Finland Sigrid Juselius Foundation NF-SI-0508-10082 / National Institute for Health Research; National Institutes of Health Research (NIHR) G0000934; G0000649; G0601261; G0500539; G9521010D; G0600705 / Medical Research Council UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) University of Oxford 050-060-810 / Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO); Netherlands Organization for Scientific Research (NWO); Netherlands Government Swedish Heart-Lung Foundation Karolinska Institute, Kings College London; Karolinska Institutet 560183 / Novartis, Peninsula Medical School, Scottish Executive Chief Scientist's Office, Stockholm County Council Knut and AliceWallenberg Foundation; Knut & Alice Wallenberg Foundation Finnish Heart Association National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) 8691 / Swedish Medical Research Council; Swedish Medical Research Council (SMRC) LSHG-CT-2004-518153; LSHG-CT-2004-512066; LSHM-CT-2006-037197; LSHM-CT-2003-503041; QL46-CT-2002-02629; LSHM-CT-2007-037273; HEALTH-F4-2007-201413 / European Commission; European Commission Joint Research Centre 068545/Z/02; GR072960; GR076113; GR069224; 086596/Z/08/Z / Wellcome Trust Finnish Cultural Foundation, Folkhalsan Research Foundation; Finnish Cultural Foundation 1Z01-HG000024 / MedStar Research Institute, Munich Center of Health Sciences, National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Vandervell Foundation American Diabetes Association, Arthritis Research Campaign, AstraZeneca AB; American Diabetes Association; Versus Arthritis; AstraZeneca HG02651 / NHGRI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
Identifiers: 9937443808331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article