Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Int J Obes (Lond). 2012 Jan;36(1):159-63. doi: 10.1038/ijo.2011.86. Epub 2011 Apr 19.
Recent genome-wide association studies (GWAS) have identified 38 obesity-associated loci among European populations. However, their contribution to obesity in other ethnicities is largely unknown.
We utilised five GWAS (N=10 482) from Chinese (three cohorts, including one with type 2 diabetes and another one of children), Malay and Indian ethnic groups from Singapore. Data sets were analysed individually and subsequently in combined meta-analysis for Z-score body-mass index (BMI) associations.
Variants at the FTO locus showed the strongest associations with BMI Z-score after meta-analysis (P-values 1.16 × 10(-7)-7.95 × 10(-7)). We further detected associations with nine other index obesity variants close to the MC4R, GNPDA2, TMEM18, QPCTL/GIPR, BDNF, ETV5, MAP2K5/SKOR1, SEC16B and TNKS/MSRA loci (meta-analysis P-values ranging from 3.58 × 10(-4)-1.44 × 10(-2)). Three other single-nucleotide polymorphisms (SNPs) from CADM2, PTBP2 and FAIM2 were associated with BMI (P-value ≤ 0.0418) in at least one dataset. The neurotrophin/TRK pathway (P-value=0.029) was highlighted by pathway-based analysis of loci that had statistically significant associations among Singaporean populations.
Our data confirm the role of FTO in obesity predisposition among Chinese, Malays and Indians, the three major Asian ethnic groups. We additionally detected associations for 12 obesity-associated SNPs among Singaporeans. Thus, it is likely that Europeans and Asians share some of the genetic predisposition to obesity. Furthermore, the neurotrophin/TRK signalling may have a central role for common obesity among Asians.
最近的全基因组关联研究（GWAS）已经在欧洲人群中鉴定出 38 个与肥胖相关的基因座。然而，它们在其他种族中的肥胖贡献在很大程度上是未知的。
我们利用了来自新加坡的中国（三个队列，包括一个 2 型糖尿病队列和一个儿童队列）、马来族和印度族的五项 GWAS（N=10482）。数据分别进行分析，然后进行合并元分析，以获得 Z 分数体重指数（BMI）的关联。
在元分析后，FTO 基因座的变异与 BMI Z 分数的关联最强（P 值为 1.16×10(-7)-7.95×10(-7)）。我们还检测到了与 MC4R、GNPDA2、TMEM18、QPCTL/GIPR、BDNF、ETV5、MAP2K5/SKOR1、SEC16B 和 TNKS/MSRA 基因座附近的另外 9 个肥胖指数变异体的关联（元分析 P 值范围为 3.58×10(-4)-1.44×10(-2)）。CADM2、PTBP2 和 FAIM2 中的另外三个单核苷酸多态性（SNP）在至少一个数据集中与 BMI 相关（P 值≤0.0418）。基于在新加坡人群中有统计学显著关联的基因座的基于途径的分析，突出了神经营养素/TRK 途径（P 值=0.029）。
我们的数据证实了 FTO 在中国人、马来人和印度人（亚洲三个主要种族）中肥胖易感性的作用。我们还在新加坡人群中检测到了 12 个与肥胖相关的 SNP 的关联。因此，欧洲人和亚洲人可能有一些共同的肥胖遗传易感性。此外，神经营养素/TRK 信号可能在亚洲人的常见肥胖中起核心作用。
