The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Curr Opin Genet Dev. 2018 Jun;50:86-95. doi: 10.1016/j.gde.2018.02.009. Epub 2018 Mar 9.
Genome-wide discovery efforts have identified more than 500 genetic loci associated with adiposity traits. The vast majority of these loci were found through large-scale meta-analyses for body mass index (BMI) and waist-to-hip ratio (WHR), and in European ancestry populations. However, alternative approaches, focusing on non-European ancestry populations, more refined adiposity measures, and low-frequency (minor allele frequency (MAF)<5%) coding variants, identified additional novel loci that had not been identified before. Loci associated with overall obesity implicate pathways that act in the brain, whereas loci associated with fat distribution point to pathways involved in adipocyte biology. Pinpointing the causal gene within each locus remains challenging, but is a critical step towards translation of genome-wide association study (GWAS) loci into new biology. Ultimately, new genes may provide pharmacological targets for the development of weight loss drugs.
全基因组发现工作已经确定了 500 多个与肥胖特征相关的遗传位点。这些位点中的绝大多数是通过针对体重指数 (BMI) 和腰臀比 (WHR) 的大规模荟萃分析以及在欧洲血统人群中发现的。然而，关注非欧洲血统人群、更精细的肥胖测量方法以及低频 (次要等位基因频率 (MAF)<5%) 编码变体的替代方法，确定了以前未发现的其他新位点。与整体肥胖相关的位点涉及作用于大脑的途径，而与脂肪分布相关的位点则指向涉及脂肪细胞生物学的途径。确定每个位点中的因果基因仍然具有挑战性，但这是将全基因组关联研究 (GWAS) 位点转化为新生物学的关键步骤。最终，新基因可能为开发减肥药提供药理学靶点。
