Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Obesity (Silver Spring). 2012 Mar;20(3):622-7. doi: 10.1038/oby.2011.154. Epub 2011 Jun 23.
Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with obesity in Europeans but results in other ethnicities are less convincing. Here, we report a two-stage GWAS of BMI in African Americans. The GWAS was performed using the Affymetrix 6.0 platform in 816 nondiabetic and 899 diabetic nephropathy subjects. 746,626 single-nucleotide polymorphisms (SNPs) were tested for association with BMI after adjustment for age, gender, disease status, and population structure. Sixty high scoring SNPs that showed nominal association in both GWAS cohorts were further replicated in 3,274 additional subjects in four replication cohorts and a meta-analysis was computed. Meta-analysis of 4,989 subjects revealed five SNPs (rs6794092, rs268972, rs2033195, rs815611, and rs6088887) at four loci showing consistent associations in both GWAS (P < 0.0001) and replication cohorts (P < 0.05) with combined P values range from 2.4 × 10(-6) to 5 × 10(-5). These loci are located near PP13439-TMEM212, CDH12, MFAP3-GALNT10, and FER1L4 and had effect sizes between 0.091 and 0.167 s.d. unit (or 0.67-1.24 kg/m(2)) of BMI for each copy of the effect allele. Our findings suggest the presence of novel loci potentially associated with adiposity in African Americans. Further replication and meta-analysis in African Americans and other populations will shed light on the role of these loci in different ethnic populations.
最近的全基因组关联研究（GWAS）已经确定了多个与欧洲人体重相关的新基因座，但在其他种族中的结果则不太令人信服。在这里，我们报告了一项针对非裔美国人 BMI 的两阶段 GWAS 研究。GWAS 使用 Affymetrix 6.0 平台在 816 名非糖尿病和 899 名糖尿病肾病患者中进行。在调整年龄、性别、疾病状态和人口结构后，对 746626 个单核苷酸多态性（SNP）与 BMI 进行关联测试。在两个 GWAS 队列中都显示出名义关联的 60 个高分 SNP 在四个复制队列中的另外 3274 名受试者中进一步复制，并进行了荟萃分析。在 4989 名受试者的荟萃分析中，在两个 GWAS （P < 0.0001）和复制队列（P < 0.05）中都显示出一致关联的四个基因座中的五个 SNP（rs6794092、rs268972、rs2033195、rs815611 和 rs6088887），合并 P 值范围从 2.4×10(-6)到 5×10(-5)。这些基因座位于 PP13439-TMEM212、CDH12、MFAP3-GALNT10 和 FER1L4 附近，每个效应等位基因的 BMI 效应大小在 0.091 到 0.167 个标准差单位（或 0.67-1.24kg/m(2)）之间。我们的研究结果表明，非裔美国人中存在可能与肥胖相关的新基因座。在非裔美国人和其他人群中的进一步复制和荟萃分析将阐明这些基因座在不同种族人群中的作用。
