However, in populations of African ancestry, the correlation between SNPs in FTO’s first intron is substantially weaker than in European or East Asian ancestry populations (Figure 1b). This looser correlation structure provides the opportunity to narrow down to chromosomal region in which the causal variant(s) might be located. For example, a large-scale GWAS in African ancestry populations that combined data from 45,849 individuals, identified rs17817964 as the most significantly BMI-associated FTO SNP.26 In populations of European and East Asian ancestry, rs17817964 is part of the same large cluster described above, whereas in African ancestry populations, rs17817964 represents a cluster of much fewer SNPs across a smaller region, thus narrowing the locus that harbors the causal FTO variant (Figure 1b). In a targeted fine-mapping effort by the PAGE (Population Architecture using Genomics and Epidemiology) study, genotypes of 3,756 SNPs across a 646kb-region at 16q12.2, encompassing FTO and the neighboring RPGRIP1L, were tested in more than 20,000 African Americans, identifying rs56137030 as the SNP with the most significant association with BMI.27 In Europeans ancestry populations, this SNP represents a cluster (r2CEU >0.50)
