在两项研究中，研究人员在东亚人体内鉴定出一些常见性的与肥胖相关的遗传变异型(genetic variant)。
在第一项研究中，通过分析来自62000多名东亚人的数据，研究人员在基因KLF9和MSTN中鉴定出这些变异型或者说单核苷酸多态性(single nucleotide polymorphism, SNP)中的两个。KLF9是一种转录因子，能够激活参与多种生理过程(包括一种参与脂肪细胞分化和与肥胖相关联的过程)的基因表达。已知MSTN突变导致身体脂肪减少。进一步分析揭示这两个新鉴定出的SNP相互作用，这就提示着MSTN调节KLF9对身体质量指数(body mass index, BMI)产生的影响。BMI是衡量肥胖的通行标准。
在第二项研究中，研究人员对来自8项全基因组关联研究的数据进行整合分析，涉及将近28000名东亚人基因组中大约240万个SNP。这项研究在三种已证实与BMI相关联的基因FTO、SEC16B和MC4R中鉴定出SNP。
在对来自另外55000名东亚人的数据进行分析之后，来自日本理化学研究所的Yukinori Okada、Toshihiro Tanaka和同事们着重关注他们发现与BMI相关联的798个SNP，以及在较早前研究中发现与BMI相关联的另外50个SNP。通过将这些数据集结合在一起，他们证实之前发现与欧洲人肥胖相关联的6个基因中的SNP也显著性地与东亚人BMI相关联。
研究人员也鉴定出3个之前未知的与BMI显著性相关联的变异位于或靠近基因CDKAL1、PCSK1和GP2。
在这些所有被鉴定的变异型中，FTO变异型最为强烈地与BMI相关联，而且它将近占参与研究者个体变异的0.2%。这种变异型与9个与BMI相关联的其他基因大约占研究参与者之间个体变异的0.9%，而全部22个被鉴定出的基因一起也只占研究参与者之间个体变异的1.18%。
类似这样的大规模研究提供关于肥胖遗传基础方面有价值的信息。通过鉴定在东亚人体内发挥重要作用的遗传变异型，研究人员就可以将它们与欧洲人携带的遗传型进行比较。(生物谷：Bioon.com)
本文编译自Finding genes that expand waistlines
doi: 10.1038/ng.1086
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Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations
Yukinori Okada, Michiaki Kubo, Hiroko Ohmiya et al.
Obesity is a disorder with a complex genetic etiology, and its epidemic is a worldwide problem. Although multiple genetic loci associated with body mass index, the most common measure of obesity, have been identified in European populations, few studies have focused on Asian populations. Here we report a genome-wide association study and replication studies with 62,245 east Asian subjects, which identified two new body mass index–associated loci in the CDKAL1 locus at 6p22 (rs2206734, P = 1.4 × 10−11) and the KLF9 locus at 9q21 (rs11142387, P = 1.3 × 10−9), as well as several previously reported loci (the SEC16B, BDNF, FTO, MC4R and GIPR loci, P < 5.0 × 10−8). We subsequently performed gene-gene interaction analyses and identified an interaction (P = 2.0 × 10−8) between a SNP in the KLF9 locus (rs11142387) and one in the MSTN (also known as GDF8) locus at 2q32 (rs13034723). These findings should provide useful insights into the etiology of obesity.
doi: 10.1038/ng.1087
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Meta-analysis identifies common variants associated with body mass index in east Asians
Wanqing Wen,Yoon-Shin Cho, Wei Zheng, Rajkumar Dorajoo et al.
Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 × 10−8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 × 10−7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.
