The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents

Objective: To investigate possible age-related changes in associations between polymorphisms in the fat mass and obesity-associated (FTO) gene and higher body mass index (BMI).Design and Subjects: Multilevel mixed regression models were used to examine associations between four FTO variants and longitudinal BMI profiles in non-Hispanic white and African American children and adolescents 8-17 years of age from two different longitudinal cohort studies, the Bogalusa Heart Study (BHS) and Project HeartBeat! (PHB). In the BHS, there were 1551 examinations of 478 African Americans and 3210 examinations of 1081 non-Hispanic whites; in PHB, there were 971 examinations of 131 African Americans and 4458 examinations of 505 non-Hispanic whites. Results: In African Americans, no significant FTO associations with BMI were found. In non-Hispanic whites, linkage disequilibrium among all four variants made haplotype analysis superfluous, so we focused on the single-nucleotide polymorphism, rs9939609. In longitudinal multilevel models, the AA genotype of rs9939609 was associated with higher BMI in non-Hispanic whites in both cohorts at all ages. A significant age-by-genotype interaction found only in the BHS cohort predicted that in those with the AA genotype, BMI would be 0.7kgm² higher at age 8 and 1.6kgm² higher at age 17 than in those with AT or TT genotypes. The design of PHB limited follow-up of any single individual to 4 years, and may have reduced the ability to detect any age-by-genotype interaction in this cohort. Conclusions: The AA genotype of rs9939609 in the FTO gene is associated with higher longitudinal BMI profiles in non-Hispanic whites from two different cohorts. The association may change with age, with the AA genotype being associated with a larger BMI difference in late adolescence than in childhood, though this was observed only in the BHS cohort and requires verification.