PLoS Genetics (Jun 2009)

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 Nordström,
  • Peter Nordström,
  • Ben A Oostra,
  • Colin N A Palmer,
  • Felicity Payne,
  • John F Peden,
  • Inga Prokopenko,
  • Frida Renström,
  • 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 Consortium,
  • 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,
  • André G Uitterlinden,
  • Cornelia M van Duijn,
  • Nicholas J Wareham,
  • Hugh Watkins,
  • Procardis Consortia,
  • Dawn M Waterworth,
  • Michael Boehnke,
  • Panos Deloukas,
  • Leif Groop,
  • David J Hunter,
  • Unnur Thorsteinsdottir,
  • David Schlessinger,
  • H-Erich Wichmann,
  • Timothy M Frayling,
  • Gonçalo R Abecasis,
  • Joel N Hirschhorn,
  • Ruth J F Loos,
  • Kari Stefansson,
  • Karen L Mohlke,
  • Inês Barroso,
  • Mark I McCarthy,
  • Giant Consortium

DOI
https://doi.org/10.1371/journal.pgen.1000508
Journal volume & issue
Vol. 5, no. 6
p. e1000508

Abstract

Read online

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.