Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama, Japan.
Nat Genet. 2012 Feb 19;44(3):302-6. doi: 10.1038/ng.1086.
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.
肥胖是一种具有复杂遗传病因的疾病，其流行是一个全球性问题。虽然已经在欧洲人群中鉴定出多个与体重指数（肥胖的最常用衡量标准）相关的遗传位点，但很少有研究关注亚洲人群。在这里，我们报告了一项全基因组关联研究和对 62245 名东亚受试者的复制研究，该研究在 6p22 上的 CDKAL1 基因座（rs2206734，P = 1.4×10(-11))和 9q21 上的 KLF9 基因座（rs11142387，P = 1.3×10(-9))发现了两个与体重指数相关的新基因座，以及几个先前报道的基因座（SEC16B、BDNF、FTO、MC4R 和 GIPR 基因座，P<5.0×10(-8))。随后，我们进行了基因-基因相互作用分析，并鉴定出 KLF9 基因座(rs11142387)中的一个 SNP 与 2q32 上的 MSTN（也称为 GDF8）基因座(rs13034723)中的一个 SNP 之间存在相互作用（P=2.0×10(-8))。这些发现应该为肥胖的病因提供有用的见解。
