近日,着名国际期刊nature发表了多国科学家共同研究的一项最新成果,他们对大量人群进行了全基因组关联性分析,发现了许多影响人体脂肪分布的基因。这一研究成果为进一步了解基因如何影响人体脂肪分布和肥胖提供了重要启示。
研究人员指出,身体的脂肪分布是一种遗传性状,同时也是预测代谢不良结果的有效指标,不依赖于全身性肥胖。为进一步理解脂肪分布的基因基础以及其与心脏代谢特征的分子联系,研究人员对多达224459个人的腰围臀围相关特征进行了全基因组关联性分析。结果发现49个位点(33个新位点)与进行了BMI矫正后的腰臀比具有相关性,另外新发现有19个位点与腰围臀围测量结果具有相关性(P < 5 × 10?8)。<>
在这49个位点中有20个表现出性别差异,这20个位点中有19个位点在女性中表现出很强的效应。研究人员鉴定出的位点主要富集在脂肪组织表达的基因以及脂肪细胞的调控元件中。同时,信号通路分析暗示脂肪生成,血管生成,转录调控和胰岛素抵抗均能够影响脂肪分布,这项研究为深入了解影响脂肪分布的潜在生理机制具有重要意义。
综上所述,该文章应用GWAS分析发现了49个影响人体脂肪分布的基因位点,这些位点富集在影响脂肪生成,转录调控等多条通路中。这项研究为我们了解基因与脂肪分布和肥胖的关系提供了重要启示。
访问英文原文点这里 doi:10.1038/nature14132
New genetic loci link adipose and insulin biology to body fat distribution
Dmitry Shungin,Thomas W. Winkler,Damien C. Croteau-Chonka,Teresa Ferreira,Adam E. Locke,Reedik M?gi, Rona J. Strawbridge, Tune H. Pers, Krista Fischer,Anne E. Justice, Tsegaselassie Workalemahu, Joseph M. W. Wu, Martin L. Buchkovich, Nancy L. Heard-Costa, Tamara S. Roman, Alexander W. Drong, Ci Song, Stefan Gustafsson, Felix R. Day, Tonu Esko, Tove Fall, Zoltán Kutalik, Joshua C. Randall, André Scherag et al.
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.<>
来源:生物谷