全基因组关联扫描荟萃分析确定了影响肥胖和脂肪分布的三个基因座。
Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
作者信息
Lindgren Cecilia M, Heid Iris M, Randall Joshua C, Lamina Claudia, Steinthorsdottir Valgerdur, Qi Lu, Speliotes Elizabeth K, Thorleifsson Gudmar, Willer Cristen J, Herrera Blanca M, Jackson Anne U, Lim Noha, Scheet Paul, Soranzo Nicole, Amin Najaf, Aulchenko Yurii S, Chambers John C, Drong Alexander, Luan Jian'an, Lyon Helen N, Rivadeneira Fernando, Sanna Serena, Timpson Nicholas J, Zillikens M Carola, Zhao Jing Hua, Almgren Peter, Bandinelli Stefania, Bennett Amanda J, Bergman Richard N, Bonnycastle Lori L, Bumpstead Suzannah J, Chanock Stephen J, Cherkas Lynn, Chines Peter, Coin Lachlan, Cooper Cyrus, Crawford Gabriel, Doering Angela, Dominiczak Anna, Doney Alex S F, Ebrahim Shah, Elliott Paul, Erdos Michael R, Estrada Karol, Ferrucci Luigi, Fischer Guido, Forouhi Nita G, Gieger Christian, Grallert Harald, Groves Christopher J, Grundy Scott, Guiducci Candace, Hadley David, Hamsten Anders, Havulinna Aki S, Hofman Albert, Holle Rolf, Holloway John W, Illig Thomas, Isomaa Bo, Jacobs Leonie C, Jameson Karen, Jousilahti Pekka, Karpe Fredrik, Kuusisto Johanna, Laitinen Jaana, Lathrop G Mark, Lawlor Debbie A, Mangino Massimo, McArdle Wendy L, Meitinger Thomas, Morken Mario A, Morris Andrew P, Munroe Patricia, Narisu Narisu, Nordström Anna, Nordström Peter, Oostra Ben A, Palmer Colin N A, Payne Felicity, Peden John F, Prokopenko Inga, Renström Frida, Ruokonen Aimo, Salomaa Veikko, Sandhu Manjinder S, Scott Laura J, Scuteri Angelo, Silander Kaisa, Song Kijoung, Yuan Xin, Stringham Heather M, Swift Amy J, Tuomi Tiinamaija, Uda Manuela, Vollenweider Peter, Waeber Gerard, Wallace Chris, Walters G Bragi, Weedon Michael N, Witteman Jacqueline C M, Zhang Cuilin, Zhang Weihua, Caulfield Mark J, Collins Francis S, Davey Smith George, Day Ian N M, Franks Paul W, Hattersley Andrew T, Hu Frank B, Jarvelin Marjo-Riitta, Kong Augustine, Kooner Jaspal S, Laakso Markku, Lakatta Edward, Mooser Vincent, Morris Andrew D, Peltonen Leena, Samani Nilesh J, Spector Timothy D, Strachan David P, Tanaka Toshiko, Tuomilehto Jaakko, Uitterlinden André G, van Duijn Cornelia M, Wareham Nicholas J, Waterworth Dawn M, Boehnke Michael, Deloukas Panos, Groop Leif, Hunter David J, Thorsteinsdottir Unnur, Schlessinger David, Wichmann H-Erich, Frayling Timothy M, Abecasis Gonçalo R, Hirschhorn Joel N, Loos Ruth J F, Stefansson Kari, Mohlke Karen L, Barroso Inês, McCarthy Mark I
机构信息
Wellcome Trust Centre for Human Genetics, University of Oxford, , Oxford, United Kingdom.
出版信息
PLoS Genet. 2009 Jun;5(6):e1000508. doi: 10.1371/journal.pgen.1000508. Epub 2009 Jun 26.
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.
为了确定影响中心性肥胖和脂肪分布的基因位点，我们对16项全基因组关联研究（GWAS，N = 38,580）进行了荟萃分析，这些研究提供了成人腰围（WC）和腰臀比（WHR）的信息。我们选择了26个单核苷酸多态性（SNP）进行后续研究，这些SNP与中心性肥胖指标（WC和/或WHR）的关联证据充分，且与总体肥胖或身高的关联证据不成比例。在最多70,689名个体中进行的后续研究确定了两个与中心性肥胖指标密切相关的基因位点；它们位于TFAP2B附近（WC，P = 1.9x10(-11)）和MSRA附近（WC，P = 8.9x10(-9)）。第三个基因位点位于LYPLAL1附近，仅与女性的WHR相关（P = 2.6x10(-8)）。TFAP2B附近的变异似乎通过对总体肥胖/脂肪量的影响来影响中心性肥胖，而LYPLAL1仅与女性的脂肪分布有很强的关联。通过关注中心性肥胖和脂肪分布的人体测量指标，我们确定了三个与人类肥胖调节有关的基因位点。
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