Life stage-specific effects of genetic susceptibility to higher body size on body fat and lean mass: prospective cohort study

Background/ObjectivesSeparate genetic variants are associated with larger body size in childhood and adulthood. Whether these variants predominantly influence adiposity, and whether these truly differ by life stage is unknown. We examined how genetic variants influence total body fat and total lean mass trajectories from childhood to young adulthood. MethodsData were from the Avon Longitudinal Study of Parents and Children birth cohort. Sex-specific genetic risk scores (GRS) for childhood and adulthood body size were generated, and dual-energy X-ray absorptiometry scans were used to measure total body fat and lean mass 6 times between ages 9-25y. We used mutually-adjusted multilevel linear spline models to examine the independent sex-specific associations of childhood and adulthood body size GRSs with fat and lean mass trajectories from 9 -25y. ResultsIn males, the childhood and adulthood GRS were associated with similar differences in fat mass from 9 to 18y; 8.3% (95% confidence interval (CI): 5.1,11.6)) and 7.5% (95% CI: 4.3,10.8) higher fat mass at 18y per standard deviation (SD) higher childhood and adulthood GRS respectively. At 25y, childhood GRS associations with fat mass attenuated while adulthood GRS associations remained similar to those at 18y for males. Among females, associations for the childhood GRS were almost two-fold stronger than the adulthood GRS from 9 to 18y: 10.5% (95% CI: 8.5, 12.4) higher fat mass at 9y per SD higher childhood GRS compared with 5.1% (95% CI 3.2, 6.9) per SD higher adulthood GRS. At 25y, associations of the childhood and adulthood GRS with fat mass were similar; 5.0% (95% CI: 2.5, 7.5) and 5.8% (95% CI: 3.3, 8.3) higher fat mass per SD higher childhood and adulthood GRS respectively: Lean mass effect sizes were much smaller. ConclusionsGenetic variants for body size are more strongly associated with adiposity than lean mass from childhood to early adulthood; childhood variants are more strongly associated with adiposity in females until early adulthood whereas childhood and adulthood variants are similarly associated with adiposity across early life in males. Findings may inform selection of instruments for life stage-specific adiposity in future Mendelian randomization studies.