In 2007, within a time period of three months, two studies claimed the discovery of FTO as the first GWAS-identified obesity-susceptibility gene.8-10 FTO was first discovered through a GWAS of type 2 diabetes in Europeans, comparing 1,924 cases and 2,938 controls.8 A cluster of single nucleotide polymorphisms (SNPs) in the first intron of the gene showed highly significant association with risk of type 2 diabetes. However, after adjusting for BMI, the association with type 2 diabetes completely abolished, suggesting that the FTO - type 2 diabetes association was mediated through FTO’s effect on BMI. Follow-up analyses in 38,759 individuals confirmed the association with BMI and obesity risk.8 Eight weeks after the first discovery, a GWAS for BMI in 4,741 Sardinians observed highly significant associations for SNPs from the same intronic cluster in FTO, which was subsequently replicated in 2,335 European and Hispanic Americans.9 A third study, published at around the same time as the two GWAS, identified the same FTO locus serendipitously, while testing for population stratification in their case-control obesity data.10
