MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Int J Epidemiol. 2023 Oct 5;52(5):1377-1387. doi: 10.1093/ije/dyad029.
BACKGROUND/OBJECTIVES: Different genetic variants are associated with larger body size in childhood vs adulthood. Whether and when these variants predominantly influence adiposity are unknown. We examined how genetic variants influence total body fat and total lean mass trajectories.
Data were from the Avon Longitudinal Study of Parents and Children birth cohort (N = 6926). Sex-specific genetic risk scores (GRS) for childhood and adulthood body size were generated, and dual-energy X-ray absorptiometry scans measured body fat and lean mass six times between the ages of 9 and 25 years. Multilevel linear spline models examined associations of GRS with fat and lean mass trajectories.
In males, the sex-specific childhood and adulthood GRS were associated with similar differences in fat mass from 9 to 18 years; 8.3% [95% confidence interval (CI) 5.1, 11.6] and 7.5% (95% CI 4.3, 10.8) higher fat mass at 18 years per standard deviation (SD) higher childhood and adulthood GRS, respectively. In males, the sex-combined childhood GRS had stronger effects at ages 9 to 15 than the sex-combined adulthood GRS. In females, associations for the sex-specific childhood GRS were almost 2-fold stronger than the adulthood GRS from 9 to 18 years: 10.5% (95% CI 8.5, 12.4) higher fat mass at 9 years per SD higher childhood GRS compared with 5.1% (95% CI 3.2, 6.9) per-SD higher adulthood GRS. In females, the sex-combined GRS had similar effects, with slightly larger effect estimates. Lean mass effect sizes were much smaller.
Genetic variants for body size are more strongly associated with adiposity than with lean mass. Sex-combined childhood variants are more strongly associated with increased adiposity until early adulthood. This may inform future studies that use genetics to investigate the causes and impact of adiposity at different life stages.
背景/目的：不同的遗传变异与儿童期和成年期的体型较大有关。这些变异何时以及主要何时影响肥胖尚不清楚。我们研究了遗传变异如何影响全身脂肪和全身瘦体重的轨迹。
数据来自雅芳纵向研究父母和孩子的出生队列（N=6926）。生成了儿童期和成年期体型的性别特异性遗传风险评分（GRS），并在 9 至 25 岁之间使用双能 X 射线吸收法扫描六次测量体脂肪和瘦体重。多层次线性样条模型检查了 GRS 与脂肪和瘦体重轨迹的关联。
在男性中，性别特异性的儿童期和成年期 GRS 与 9 至 18 岁期间的体脂差异相似；18 岁时，每标准偏差（SD）升高 GRS，体脂分别高出 8.3%（95%CI 5.1，11.6）和 7.5%（95%CI 4.3，10.8）。在男性中，性别组合的儿童期 GRS 在 9 至 15 岁时的作用强于性别组合的成年期 GRS。在女性中，性别特异性儿童期 GRS 的关联从 9 岁到 18 岁几乎比成年期 GRS 强两倍：每 SD 升高儿童期 GRS，9 岁时体脂增加 10.5%（95%CI 8.5，12.4），而每 SD 升高成年期 GRS 则增加 5.1%（95%CI 3.2，6.9）。在女性中，性别组合的 GRS 具有相似的作用，但其效应估计值略大。瘦体重的效应大小要小得多。
与瘦体重相比，体型的遗传变异与肥胖的相关性更强。性别组合的儿童期变异与成年早期之前的肥胖增加相关性更强。这可能为未来的研究提供信息，这些研究使用遗传学来研究不同生命阶段肥胖的原因和影响。
