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; 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: Cecilia M. Lindgren - University of Oxford
Iris M. Heid - University of Regensburg
Joshua C. Randall - Wellcome Centre for Human Genetics
Claudia Lamina - Innsbruck Medical University
Valgerdur Steinthorsdottir - deCODE Genet, Reykjavik, Iceland
Lu Qi - Harvard University
Elizabeth K. Speliotes - Broad Institute
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Cristen J. Willer - University of Michigan–Ann Arbor
Blanca M. Herrera - Wellcome Centre for Human Genetics
Anne U. Jackson - University of Michigan–Ann Arbor
Noha Lim - College Station Medical Center
Paul Scheet - Michigan United
Nicole Soranzo - Wellcome Sanger Institute
Najaf Amin - Erasmus MC
Yurii S. Aulchenko - Erasmus MC
John C. Chambers - Imperial College London
Alexander Drong - Wellcome Centre for Human Genetics
Jian'an Luan - MRC Epidemiology Unit
Helen N. Lyon - Boston Children's Hospital
Fernando Rivadeneira - Erasmus MC
Serena Sanna - Institute of Genetic and Biomedical Research
Nicholas J. Timpson - University of Bristol
M. Carola Zillikens - Erasmus MC
Jing Hua Zhao - MRC Epidemiology Unit
Peter Almgren - Malmö University
Stefania Bandinelli - Azienda Sanitaria di Firenze
Amanda J. Bennett - University of Oxford
Richard N. Bergman - University of Southern California
Lori L. Bonnycastle - National Human Genome Research Institute
Suzannah J. Bumpstead - Wellcome Sanger Institute
Stephen J. Chanock - National Cancer Institute
Lynn Cherkas - King's College London
Peter Chines - National Human Genome Research Institute
Lachlan Coin - Imperial College London
Cyrus Cooper - University of Southampton
Gabriel Crawford - Broad Institute
Angela Doering - Helmholtz Zentrum München
Anna Dominiczak - University of Glasgow
Alex S. F. Doney - Ninewells Hospital
Shah Ebrahim - University of Bristol
Paul Elliott - Imperial College London
Michael R. Erdos - National Human Genome Research Institute
Karol Estrada - Erasmus MC
Luigi Ferrucci - National Institute on Aging
Guido Fischer - Helmholtz Zentrum München
Nita G. Forouhi - MRC Epidemiology Unit
Christian Gieger - Helmholtz Zentrum München
Harald Grallert - Helmholtz Zentrum München
Christopher J. Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Scott Grundy - The University of Texas Southwestern Medical Center
Candace Guiducci - Broad Institute
David Hadley - St George's, University of London
Anders Hamsten - Karolinska Institutet
Aki S. Havulinna - Institute for Molecular Medicine Finland
Albert Hofman - Erasmus MC
Rolf Holle - Helmholtz Zentrum München
John W. Holloway - University of Southampton
Thomas Illig - Helmholtz Zentrum München
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 - Oxford Centre for Diabetes, Endocrinology and Metabolism
Johanna Kuusisto - University of Helsinki
Jaana Laitinen - Finnish Inst Occpat Hlth, Oulu, Finland
G. Mark Lathrop - Centre National de Recherche en Génomique Humaine
Debbie A. Lawlor - University of Bristol
Massimo Mangino - King's College London
Wendy L. McArdle - University of Bristol
Thomas Meitinger - Helmholtz Zentrum München
Mario A. Morken - National Human Genome Research Institute
Andrew P. Morris - University of Oxford
Patricia Munroe - Queen Mary University of London
Narisu Narisu - National Human Genome Research Institute
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 - Wellcome Centre for Human Genetics
Inga Prokopenko - Wellcome Centre for Human Genetics
Frida Renstroem - Umeå University
Aimo Ruokonen - University of Oulu
Veikko Salomaa - Institute for Molecular Medicine Finland
Manjinder S. Sandhu - University of Cambridge
Laura J. Scott - University of Michigan–Ann Arbor
Angelo Scuteri - Istituti di Ricovero e Cura a Carattere Scientifico
Kaisa Silander - Institute for Molecular Medicine Finland
Kijoung Song - College Station Medical Center
Xin Yuan - College Station Medical Center
Heather M. Stringham - University of Michigan–Ann Arbor
Amy J. Swift - National Human Genome Research Institute
Tiinamaija Tuomi - University of Helsinki
Manuela Uda - Institute of Genetic and Biomedical Research
Peter Vollenweider - University Hospital of Lausanne
Gerard Waeber - University Hospital of Lausanne
Chris Wallace - William Harvey Research Institute
G. Bragi Walters - deCODE Genetics
Michael N. Weedon - Peninsula College of Medicine and Dentistry
Wellcome Trust Case Control Consor
Publication Details: PLoS genetics, Vol.5(6), pp.e1000508-e1000508
Publisher: Public Library Science
Number of pages: 13
Date published: 01/06/2009
Grant note: 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) MC_U106188470; G0000934; G0701863; G0600705; MC_qA137934; G9521010; G0801056; G0601261 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) The Barts
Identifiers: 99928751102346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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