Edinburgh Research Explorer Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution
Edinburgh Research Explorer Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution
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为了确定影响中心性肥胖和脂肪分布的遗传位点，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 SNP 进行随访，这些 SNP 与中央肥胖（腰围和/或腰臀比）测量值相关的证据很强，并且与整体肥胖或身高的相关性不成比例。对最多 70,689 名个体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座；这些地图靠近 TFAP2B (WC, P =1.9 6 10 2 11 ) 和 MSRA (WC, P =8.9 6 10 2 9 )。第三个基因座，靠近 LYPLAL1 ，仅与女性的腰臀比相关（ P =2.6 6 10 2 8 ）。 TFAP2B 附近的变异似乎通过影响整体肥胖/脂肪量来影响中心性肥胖，而 LYPLAL1 显示出与脂肪分布的强烈关联（仅限女性）。通过关注中心性肥胖和脂肪分布的人体测量指标，我们确定了与人类肥胖调节有关的三个基因座。 70,689 名个体）旨在揭示影响中心性肥胖和脂肪分布的人体测量指标的变异，即腰围（WC）和腰臀比（WHR）。这项工作补充了已成功定义影响整体肥胖的变异的并行努力，并重点关注与代谢和心血管疾病特别密切相关的内脏脂肪积累。我们的分析确定了两个与 WC 相关的基因座（TFAP2B 和 MSRA），以及靠近 LYPLAL1 的另一个基因座，该基因座显示了与 WHR 的性别特异性关系（均达到全基因组显着性水平）。这些位点与整体肥胖的关联强度各不相同，尤其是 LYPLAL1 似乎对脂肪分布模式有特定的影响。总而言之，这三个基因座为人类生理学和肥胖的发展提供了新的见解。
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 =1.9 6 10 2 11 ) and MSRA (WC, P =8.9 6 10 2 9 ). A third locus, near LYPLAL1 , was associated with WHR in women only ( P =2.6 6 10 2 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. 70,689 individuals) designed to uncover variants influencing anthropometric measures of central obesity and fat distribution, namely waist circumference (WC) and waist–hip ratio (WHR). This work complements parallel efforts that have been successful in defining variants impacting overall adiposity and focuses on the visceral fat accumulation which has particularly strong relationships to metabolic and cardiovascular disease. Our analyses have identified two loci ( TFAP2B and MSRA ) associated with WC, and a further locus, near LYPLAL1 , which shows gender-specific relation- ships with WHR (all to levels of genome-wide significance). These loci vary in the strength of their associations with overall adiposity, and LYPLAL1 in particular appears to have a specific effect on patterns of fat distribution. All in all, these three loci provide novel insights into human physiology and the development of obesity.