American Diabetes Association, Diabetes, 7(64), p. 2467-2476
The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake on BMI. We found that the BMI-increasing allele (minor allele) of FTO variant was associated with increased total energy intake (effect per allele=14.3[5.9, 22.7] kcal/day, P=6.5×10(-4)) but not with protein, carbohydrate or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele=0.08[0.03, 0.12]SDs, P for interaction=7.2×10(-4)): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele=0.10[0.07, 0.13]SDs, P=8.2×10(-10)) than in those with low intake (effect per allele=0.04[0.01, 0.07]SDs, P=0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.