Influence of common variants in FTO and near INSIG2 and MC4R on growth curves for adiposity in African- and European-American youth

Recent genome-wide association (GWA) studies identified several common variants for obesity: rs9939609 in FTO, rs7566605 near INSIG2 and both rs17782313 and rs17700633 near the MC4R gene. This study aimed to assess the influence of these polymorphisms on development of adiposity in European- (EA) and African-American (AA) youth in two ongoing longitudinal studies including 986 and 606 participants with age ranges of 10-25.8 and 4.0-23.9 years, respectively. Individual growth curve modeling was conducted separately in the two studies. We tested the effect of the SNPs on levels and increase with age (i.e., slope) of weight, body mass index (BMI), waist circumference and skinfolds from childhood to adulthood, and potential moderation by ethnicity or gender. Beta coefficients computed in the two studies were pooled using meta-analysis. Rs9939609 was associated with logtransformed levels of BMI (beta = 0.021, P = 0.01), weight (beta = 0.019, P = 0.04) and waist circumference (beta = 0.012, P = 0.04). Rs17782313 was associated with triceps (beta = 0.05, P = 0.02). Significant interactions of rs17700633 with gender were observed on subscapular-, suprailiac- and sum of skinfolds, with significant associations limited to males (P <0.05). No significant interactions with ethnicity were found. Only one effect on the slope was observed, rs17700633 showed a significant interaction with age on triceps (beta = 0.004, P = 0.04). In two longitudinal studies of EA and AA youth, we replicated the effect of FTO and common variants near MC4R on general and central adiposity. These variants did not affect the increase with age of adiposity from childhood to adulthood with one exception. Common variants for obesity identified in GWA studies have detectable but modest effects on growth curves for adiposity in EA and AA youth.