Obesity genomics: assessing the transferability of susceptibility loci across diverse populations.
Obesity genomics: assessing the transferability of susceptibility loci across diverse populations.
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作者：
Lu Y;Loos RJ
在过去的三十年里，全世界肥胖症的流行率几乎翻了一番，但各国之间存在着巨大的差异。虽然这些差异部分是由于西方化的程度，遗传因素也有贡献。到目前为止，人们对不同祖先的人群中是否有相同的基因导致肥胖易感性知之甚少。我们回顾了肥胖易感基因座的可转移性（通过全基因组关联研究确定），使用单核苷酸多态性（SNP）和基因座范围内的比较。FTO和MC4R附近的SNPs，首先在欧洲人中发现的肥胖易感性位点，在其他祖先中广泛复制。SNP对SNP的比较表明，超过一半的36个体重指数相关基因座在欧洲和东亚血统人群中共享，而基因座范围的分析表明，可转移性可能更广泛。此外，通过利用单倍型结构的差异，不同祖先的人群可以帮助缩小基因座，从而精确定位致病基因进行功能随访。将需要在祖先多样的人群中进行更大规模的遗传关联研究，以进行深入和全基因座的分析，目的是更有信心地确定基因座的可转移性，并进行精细作图。了解不同血统人群之间遗传易感性的相似性和差异，最终可能有助于更有针对性地预防和定制肥胖治疗。
The prevalence of obesity has nearly doubled worldwide over the past three decades, but substantial differences exist between nations. Although these differences are partly due to the degree of westernization, genetic factors also contribute. To date, little is known about whether the same genes contribute to obesity-susceptibility in populations of different ancestry. We review the transferability of obesity-susceptibility loci (identified by genome-wide association studies) using both single nucleotide polymorphism (SNP) and locus-wide comparisons. SNPs in FTO and near MC4R, obesity-susceptibility loci first identified in Europeans, replicate widely across other ancestries. SNP-to-SNP comparisons suggest that more than half of the 36 body mass index-associated loci are shared across European and East Asian ancestry populations, whereas locus-wide analyses suggest that the transferability might be even more extensive. Furthermore, by taking advantage of differences in haplotype structure, populations of different ancestries can help to narrow down loci, thereby pinpointing causal genes for functional follow-up. Larger-scale genetic association studies in ancestrally diverse populations will be needed for in-depth and locus-wide analyses aimed at determining, with greater confidence, the transferability of loci and allowing fine-mapping. Understanding similarities and differences in genetic susceptibility across populations of diverse ancestries might eventually contribute to a more targeted prevention and customized treatment of obesity.
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通讯作者：
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