FTO genetic variation and association with obesity in West Africans and African Americans.
FTO genetic variation and association with obesity in West Africans and African Americans.
复制标题
作者：
Adeyemo A;Chen G;Zhou J;Shriner D;Doumatey A;Huang H;Rotimi C
FTO基因是肥胖症最稳定的复制基因之一。然而，来自非洲血统人口的数据有限。我们评估了FTO基因的遗传变异，并调查了西非人和非裔美国人与肥胖的关系。研究样本包括968名非洲裔美国人(59%女性，平均年龄49岁，平均体重指数30.8公斤/平方米)和517名西非人(58%女性，平均年龄54岁，平均体重指数25.5公斤/平方米)。通过对全基因的262个标签单核苷酸多态(SNPs)进行基因分型，评估FTO的遗传变异。在加性模型下，研究了每个SNP与BMI、腰围和脂肪质量百分比的关系。正如预期的那样，这两个非洲血统样本与其他大陆(例如欧洲)群体相比，表现出较弱的连锁不平衡(LD)模式。在两个研究样本中，除了内含子1外，还有几个内含子8 SNPs显示出显著的相关性。Meta分析显示，单核苷酸多态对体重指数的综合效应分别为0.77 kg/m2(P=0.009，rs9932411)和0.7 kg/m2(P=0.006，rs7191513)。先前报道的两个与内含子1 SNPs相关的基因(rs1121980和rs7204609，R2=0.001)在西非人中重复出现。与其他大陆人群相比，非洲血统人群的FTO基因在等位基因频率和LD模式上表现出显著差异。尽管存在这些差异，但我们观察到了非裔美国人和西非人与肥胖有关的证据，以及相关的异质性证据。需要对多民族FTO进行更多的研究。
The FTO gene is one of the most consistently replicated loci for obesity. However, data from populations of African ancestry are limited. We evaluated genetic variation in the FTO gene and investigated associations with obesity in West Africans and African Americans. The study samples comprised 968 African Americans (59% female, mean age 49 years, mean BMI 30.8 kg/m2) and 517 West Africans (58% female, mean age 54 years, mean BMI 25.5 kg/m2). FTO genetic variation was evaluated by genotyping 262 tag single nucleotide polymorphisms (SNPs) across the entire gene. Association of each SNP with BMI, waist circumference, and percent fat mass was investigated under an additive model. As expected, both African-ancestry samples showed weaker linkage disequilibrium (LD) patterns compared with other continental (e.g., European) populations. Several intron 8 SNPs, in addition to intron 1 SNPs, showed significant associations in both study samples. The combined effect size for BMI for the top SNPs from meta-analysis was 0.77 kg/m2 (P = 0.009, rs9932411) and 0.70 kg/m2 (P = 0.006, rs7191513). Two previously reported associations with intron 1 SNPs (rs1121980 and rs7204609, r2 = 0.001) were replicated among the West Africans. The FTO gene shows significant differences in allele frequency and LD patterns in populations of African ancestry compared with other continental populations. Despite these differences, we observed evidence of associations with obesity in African Americans and West Africans, as well as evidence of heterogeneity in association. More studies of FTO in multiple ethnic groups are needed.
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