Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations.

Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations.
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DOI:
10.1038/ng.1086
复制
发表时间:
2012-02-19
期刊:
影响因子:
30.8
通讯作者:
Tanaka, Toshihiro
Tanaka, Toshihiro
中科院分区:
生物学1区
文献类型:
--
作者:
Okada, Yukinori;Kubo, Michiaki;Ohmiya, Hiroko;Takahashi, Atsushi;Kumasaka, Natsuhiko;Hosono, Naoya;Maeda, Shiro;Wen, Wanqing;Dorajoo, Rajkumar;Go, Min Jin;Zheng, Wei;Kato, Norihiro;Wu, Jer-Yuarn;Lu, Qi;Tsunoda, Tatsuhiko;Yamamoto, Kazuhiko;Nakamura, Yusuke;Kamatani, Naoyuki;Tanaka, Toshihiro

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肥胖是一种具有复杂遗传病因的疾病,其流行是一个世界性问题。尽管在欧洲人群中已经发现了与体重指数(BMI)(最常见的肥胖指标)相关的多个基因位点,但很少有研究关注亚洲人群。在这里,我们报告了一项针对 62,245 名东亚受试者的全基因组关联研究 (GWAS) 和复制研究,该研究在 6p22 的 CDKAL1 基因座 (rs2206734,P = 1.4 × 10−11) 和 9q21 的 KLF9 基因座 (rs11142387,P = 1.3 × 10−9) 中确定了两个新的 BMI 相关基因座。如先前报道的基因座(SEC16B、BDNF、FTO、MC4R 和 GIPR 基因座;P < 5.0 × 10−8)。我们随后进行了基因-基因相互作用分析,并确定了 KLF9 基因座 (rs11142387) 中的 SNP 和 2q32 处的 GDF8 基因座 (rs13034723) 中的 SNP 之间的相互作用 (P = 2.0 × 10−8)。这些发现应该为肥胖的病因学提供有用的见解。
Obesity is a disorder with complex genetic etiology, and its epidemic is a worldwide problem. Although multiple genetic loci associated with body mass index (BMI), 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 (GWAS) and replication studies with 62,245 East Asian subjects, which identified two novel BMI-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 previously reported loci (the SEC16B, BDNF, FTO, MC4R, and GIPR loci; P < 5.0 × 10−8). We subsequently performed gene–gene interaction analysis and identified an interaction (P = 2.0 × 10−8) between SNPs in the KLF9 locus (rs11142387) and the GDF8 locus at 2q32 (rs13034723). These findings should provide useful insights into the etiology of obesity.
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