Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
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DOI:
10.1038/ng.685
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发表时间:
2010-11
期刊:
影响因子:
30.8
通讯作者:
--
中科院分区:
生物学1区
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--
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腰臀比(WHR)是一个衡量身体脂肪分布的指标,也是一个独立于整体肥胖的代谢结果的预测指标。腰臀比是可遗传的,但很少有影响这一性状的遗传变异已被确定。我们对32项调整体重指数的WHR全基因组关联研究(多达77,167名参与者)进行了荟萃分析,并对另外29项研究(多达113,636名受试者)中的16个位点进行了随访。我们在RSPO 3、VEGFA、TBX 15-WARS 2、NFE 2L 3、GRB 14、DNM 3-PIGC、ITPR 2-SSPN、LY 86、HOXC 13、ADAMTS 9、ZNRF 3-KREMEN 1、NISCH-STAB 1和CPEB 4(P 1.9 × 10−9至1.8 × 10−40)中或附近发现了13个新基因座,并在LYPLAL 1处发现了已知信号。其中7个位点表现出明显的性别二态性,所有位点对女性WHR的影响都强于男性(性别差异P为1.9 × 10−3至1.2 × 10−13)。这些发现为多个基因座调节体脂分布提供了证据,独立于整体肥胖,并揭示了强大的基因与性别的相互作用。
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body-mass-index (up to 77,167 participants), following up 16 loci in an additional 29 studies (up to 113,636 subjects). We identified 13 novel loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1, and CPEB4 (P 1.9 × 10−9 to 1.8 × 10−40), and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex-difference 1.9 × 10−3 to 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution, independent of overall adiposity, and reveal powerful gene-by-sex interactions.
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