Lu Yingchang, Loos Ruth Jf
The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA ; The Charles Bronfman Institute of Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA ; The Charles Bronfman Institute of Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA ; The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA ; The Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Genome Med. 2013 Jun 28;5(6):55. doi: 10.1186/gm459. eCollection 2013.
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.
在过去三十年里，全球肥胖症患病率几乎翻了一番，但各国之间存在显著差异。尽管这些差异部分归因于西化程度，但遗传因素也有影响。迄今为止，对于不同血统人群中是否由相同基因导致肥胖易感性，人们知之甚少。我们使用单核苷酸多态性（SNP）和全基因座比较，来综述肥胖易感性基因座（通过全基因组关联研究确定）的可转移性。首先在欧洲人群中发现的肥胖易感性基因座FTO和MC4R附近的SNP，在其他血统人群中广泛重复出现。SNP与SNP比较表明，36个与体重指数相关的基因座中，超过一半在欧洲和东亚血统人群中是共享的，而全基因座分析表明可转移性可能更广泛。此外，利用单倍型结构的差异，不同血统的人群有助于缩小基因座范围，从而确定功能后续研究的因果基因。需要在更多不同血统人群中开展更大规模的遗传关联研究，以进行深入和全基因座分析，从而更有信心地确定基因座的可转移性并实现精细定位。了解不同血统人群在遗传易感性方面的异同，最终可能有助于更有针对性地预防肥胖和进行个性化治疗。
