Gene-by-age effects on BMI from birth to adulthood: the Fels Longitudinal Study.

Objectives Genome wide association studies have shown 32 loci to influence BMI in European-American adults but replication in other studies is inconsistent and may be attributed to gene-by-age effects. The aims of this study were to determine if the influence of the summed risk score of these 32 loci (GRS) on BMI differed across age from birth to 40 years, and to determine if additive genetic effects other than those in the GRS differed by age. Methods Serial measures of BMI were calculated at 0, 1, 3, 6, 9, 12, 18, and 28 months, and 4, 7, 11, 15, 19, 23, 30, and 40 years for 1,176 (605 females, 571 males) European-American participants in the Fels Longitudinal Study. SOLAR was used for genetic analyses. Results GRS was significant (P < 0.05) at ages: 6, 9 months, 4-15 years, and 23-40 years. Remaining additive genetic effects independently influenced BMI (P < 5.3 × 10−5, 0.40 < h2 < 0.76). Some genetic correlations between ages were not significant. Differential GRS effects did not retain significance after multiple comparisons adjustments. Conclusions While well-known BMI variants do not appear to have significant differential effects, other additive genes differ over the lifespan.