The genetics of adiposity.
The genetics of adiposity.
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DOI：
10.1016/j.gde.2018.02.009
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发表时间：
2018-06
影响因子：
4
通讯作者：
Loos RJ
中科院分区：
文献类型：
--
作者：
Loos RJ
全基因组发现工作已经确定了500多个与肥胖性状相关的遗传位点。这些基因座中的绝大多数是通过对体重指数（BMI）和腰臀比（WHR）的大规模荟萃分析以及欧洲血统人群中发现的。然而，替代方法，专注于非欧洲血统人群，更精确的肥胖测量，和低频（次要等位基因频率（MAF）< 5%）编码变异，确定了以前没有发现的额外的新基因座。与整体肥胖相关的基因座涉及大脑中作用的途径，而与脂肪分布相关的基因座则指向与脂肪细胞生物学相关的途径。精确定位每个位点内的致病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一步。最终，新的基因可能为减肥药物的开发提供药理学靶点。
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 which 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.
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