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

Author:
  • 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 Nordstrom
  • Ben A. Oostra
  • Colin N. A. Palmer
  • Felicity Payne
  • John F. Peden
  • Inga Prokopenko
  • Frida Renstrom
  • 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 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
  • 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
  • Ines Barroso
  • Mark I. McCarthy
Publishing year: 2010
Language: English
Publication/Series: PLoS Genetics
Volume: 5
Issue: 6
Document type: Journal article
Publisher: Public Library of Science

Abstract english

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 = 2.66x10(-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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Endocrinology
  • ISSN: 1553-7404
Paul Franks
E-mail: paul [dot] franks [at] med [dot] lu [dot] se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49

60-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00