Results of targeted replication of FTO in Africans and African Americans have been inconsistent,27,59-74 which may be due to the substantial differences in correlation structure between FTO SNPs in African compared to European/Asian ancestry populations (Figure 1b). As such, an FTO SNP that is part of the larger ‘European/Asian’ cluster, but that does not overlap with the ‘African’ cluster, will likely not show association with obesity related traits. However, in the recent large-scale GWAS in African ancestry populations, SNPs in FTO were among the most significantly associated with BMI, firmly establishing FTO as an obesity-susceptibility locus also in this ancestry.26 While FTO’s effect on BMI was similar to that observed in European ancestry populations, the minor allele frequency was much lower (12%) (Figure 2), such that only 0.10% of the variation of BMI in African ancestry populations was explained (Table 1).26
