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与身体脂肪分布相关的心血管代谢特征

在本期发表的来自GIANT Consortium的两篇论文的第一篇当中,对超过20万人的腰围和臀围相关特征所做的全基因组关联元分析结果,被用来识别与根据体重指数调整后的腰围-臀围比有关的49个位点(其中33个是新位点)和另外19个与相关腰围和臀围数值有关的位点。

这些位点中的一个子类显示了显著的性别二态性,其中很多在女性中效应更强。分析表明,脂肪生成、血管生成、转录调控和胰岛素抗性是影响脂肪分布的过程,这为了解潜在的病理生理机制提供了信息,也为在与腹部脂肪积累相关的风险中采取干预措施提供了潜在目标。


Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

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