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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.


ABSTRACT: 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.

SUBMITTER: Lindgren CM 

PROVIDER: S-EPMC2695778 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

Lindgren Cecilia M CM   Heid Iris M IM   Randall Joshua C JC   Lamina Claudia C   Steinthorsdottir Valgerdur V   Qi Lu L   Speliotes Elizabeth K EK   Thorleifsson Gudmar G   Willer Cristen J CJ   Herrera Blanca M BM   Jackson Anne U AU   Lim Noha N   Scheet Paul P   Soranzo Nicole N   Amin Najaf N   Aulchenko Yurii S YS   Chambers John C JC   Drong Alexander A   Luan Jian'an J   Lyon Helen N HN   Rivadeneira Fernando F   Sanna Serena S   Timpson Nicholas J NJ   Zillikens M Carola MC   Zhao Jing Hua JH   Almgren Peter P   Bandinelli Stefania S   Bennett Amanda J AJ   Bergman Richard N RN   Bonnycastle Lori L LL   Bumpstead Suzannah J SJ   Chanock Stephen J SJ   Cherkas Lynn L   Chines Peter P   Coin Lachlan L   Cooper Cyrus C   Crawford Gabriel G   Doering Angela A   Dominiczak Anna A   Doney Alex S F AS   Ebrahim Shah S   Elliott Paul P   Erdos Michael R MR   Estrada Karol K   Ferrucci Luigi L   Fischer Guido G   Forouhi Nita G NG   Gieger Christian C   Grallert Harald H   Groves Christopher J CJ   Grundy Scott S   Guiducci Candace C   Hadley David D   Hamsten Anders A   Havulinna Aki S AS   Hofman Albert A   Holle Rolf R   Holloway John W JW   Illig Thomas T   Isomaa Bo B   Jacobs Leonie C LC   Jameson Karen K   Jousilahti Pekka P   Karpe Fredrik F   Kuusisto Johanna J   Laitinen Jaana J   Lathrop G Mark GM   Lawlor Debbie A DA   Mangino Massimo M   McArdle Wendy L WL   Meitinger Thomas T   Morken Mario A MA   Morris Andrew P AP   Munroe Patricia P   Narisu Narisu N   Nordström Anna A   Nordström Peter P   Oostra Ben A BA   Palmer Colin N A CN   Payne Felicity F   Peden John F JF   Prokopenko Inga I   Renström Frida F   Ruokonen Aimo A   Salomaa Veikko V   Sandhu Manjinder S MS   Scott Laura J LJ   Scuteri Angelo A   Silander Kaisa K   Song Kijoung K   Yuan Xin X   Stringham Heather M HM   Swift Amy J AJ   Tuomi Tiinamaija T   Uda Manuela M   Vollenweider Peter P   Waeber Gerard G   Wallace Chris C   Walters G Bragi GB   Weedon Michael N MN   Witteman Jacqueline C M JC   Zhang Cuilin C   Zhang Weihua W   Caulfield Mark J MJ   Collins Francis S FS   Davey Smith George G   Day Ian N M IN   Franks Paul W PW   Hattersley Andrew T AT   Hu Frank B FB   Jarvelin Marjo-Riitta MR   Kong Augustine A   Kooner Jaspal S JS   Laakso Markku M   Lakatta Edward E   Mooser Vincent V   Morris Andrew D AD   Peltonen Leena L   Samani Nilesh J NJ   Spector Timothy D TD   Strachan David P DP   Tanaka Toshiko T   Tuomilehto Jaakko J   Uitterlinden André G AG   van Duijn Cornelia M CM   Wareham Nicholas J NJ   Hugh Watkins   Waterworth Dawn M DM   Boehnke Michael M   Deloukas Panos P   Groop Leif L   Hunter David J DJ   Thorsteinsdottir Unnur U   Schlessinger David D   Wichmann H-Erich HE   Frayling Timothy M TM   Abecasis Gonçalo R GR   Hirschhorn Joel N JN   Loos Ruth J F RJ   Stefansson Kari K   Mohlke Karen L KL   Barroso Inês I   McCarthy Mark I MI  

PLoS genetics 20090626 6


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  ...[more]

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