Since the discovery of FTO in 2007, at least 75 additional obesity-susceptibility loci have been identified through large-scale GWAS efforts. However, the FTO locus stands out, as it has by far the largest effect size, is very common, and has the largest explained variance among individuals of European ancestry. More specifically, each additional minor (risk) allele is associated with a 0.39 kg/m2 higher BMI (equivalent to 1,130 g for a person of 1.70m tall) and a 1.20 fold increased risk of obesity (Table 1).16 Approximately 43% of the population carries one risk allele and 20% carries two risk alleles, with small variations in genotype frequencies within European ancestry populations (Figure 2). Of all BMI-associated loci identified thus far, the FTO locus explains the most of the inter-individual variation in BMI, yet only a mere 0.34%.16 As a consequence, the ability to predict a person’s risk of obesity based on their FTO genotype is poor and only slightly better than tossing a coin.30
