Dietary Intake, FTO Genetic Variants, and Adiposity: A Combined Analysis of Over 16,000 Children and Adolescents

Abstract

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 the following: 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, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 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 SD [0.03, 0.12 SD], 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 SD [0.07, 0.13 SD], P = 8.2 × 10(-10)) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], 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.

Figure 1

Forest plot of the association between FTO SNP rs9939609 and total energy intake in a fixed-effects meta-analysis of 16,097 children and adolescents. The studies are shown in boys (_B), girls (_G), or mixed case patients (_Case) and control subjects (_Control) for case-control studies and whites (_White) and African Americans (_AA) for studies with multiple ethnicities separately, sorted by sample size (smallest to largest). The β represents the difference in total energy intake per minor allele of SNP rs9939609 or a proxy (r² = 1), adjusted for age, pubertal status (if available), physical activity (if available), region (if available), and eigenvectors (GWAS data only).

Figure 2

Forest plot of the interaction between FTO SNP rs9939609 and dietary protein intake on BMI in a fixed-effects meta-analysis of 16,097 children and adolescents. The studies are shown in boys (_B), girls (_G), or mixed case patients (_Case) and control subjects (_Control) for case-control studies and whites (_White) and African Americans (_AA) for studies with multiple ethnicities separately, sorted by sample size (smallest to largest). The β represents the difference in BMI per minor allele of SNP rs9939609 or a proxy (r² = 1) comparing participants in the high–protein intake group to those in the low–protein intake group, adjusted for age, pubertal status (if available), physical activity (if available), region (if available), and eigenvectors (GWAS data only).