In European-derived populations, one of the earliest, and by far the strongest, adiposity genes identified by GWAS is FTO.11 Additional GWAS and replication studies on adiposity, childhood and adult obesity confirmed the association of FTO with adiposity and obesity in Europeans,9,12,16,17 as well as in Asians.23-25 However, recent studies in African Americans have revealed inconclusive results.12,29-32 FTO is a relatively large gene, approximately 430 kilobases (kb) in length, containing nine exons. Association studies have focused primarily on intron 1, around 47 kb in length, where it is believed that the causal variant resides. As may be expected, the LD structure of FTO differs between European- and African-derived populations, with a greater number of regions of high LD and larger LD blocks observed in individuals of European descent compared with individuals of African descent. Three SNPs in particular (rs3751812, rs8050136 and rs9939609) have been widely studied in Europeans and included in many replication studies in other populations, including African Americans. These SNPs reside in the same LD block (r2 = 0.60, HapMap YRI), located within intron 1 of FTO. However, the inconclusive findings in African Americans do not point to a definitive risk variant in this population.
