FTO Genetic Variation and Association With Obesity in West Africans and African Americans

Abstract

OBJECTIVEThe 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.RESEARCH DESIGN AND METHODSThe 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.RESULTSAs 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.CONCLUSIONSThe 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.