Obesity is an important risk factor for cardiovascular and metabolic disease. Hence, it comes as no surprise that, because of the robust association between FTO and BMI, FTO SNPs are also associated with a range of cardiometabolic traits.16,121,122 In a recent large-scale meta-analysis of 36 studies (n = up to 198,502) that examined FTO’s effects on 24 cardiometabolic traits, the BMI-increasing allele of the FTO SNP was associated with increased risk of type 2 diabetes, heart failure, coronary heart disease, ever all-cause and ischemic stroke, hypertension, dyslipidemia, metabolic syndrome, and mortality, and also with increased fasting glucose and insulin levels, 2h-OGTT glucose levels, HbA1c, blood pressure, lipid levels, liver enzymes, and inflammation markers.122 For most traits, these associations were fully mediated through FTO’s effect on BMI.122 However, there was evidence that FTO may, at least in part, increase the risk of type 2 diabetes independently of its effect on BMI,122 which is consistent with earlier observations.57,58,123
