Virginia Institute for Psychiatric and Behavior Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, United States of America.
QIMR Berghofer Medical Research Institute, Herston, Australia.
PLoS Genet. 2022 Aug 11;18(8):e1010303. doi: 10.1371/journal.pgen.1010303. eCollection 2022 Aug.
Genome-wide association studies (GWAS) have successfully identified common variants associated with BMI. However, the stability of aggregate genetic variation influencing BMI from midlife and beyond is unknown. By analysing 165,717 men and 193,073 women from the UKBiobank, we performed BMI GWAS on six independent five-year age intervals between 40 and 72 years. We then applied genomic structural equation modeling to test competing hypotheses regarding the stability of genetic effects for BMI. LDSR genetic correlations between BMI assessed between ages 40 to 73 were all very high and ranged 0.89 to 1.00. Genomic structural equation modeling revealed that molecular genetic variance in BMI at each age interval could not be explained by the accumulation of any age-specific genetic influences or autoregressive processes. Instead, a common set of stable genetic influences appears to underpin genome-wide variation in BMI from middle to early old age in men and women alike.
全基因组关联研究（GWAS）已经成功地确定了与 BMI 相关的常见变异。然而，从中年到老年影响 BMI 的综合遗传变异的稳定性尚不清楚。通过分析来自 UKBiobank 的 165717 名男性和 193073 名女性，我们在 40 至 72 岁之间的六个独立的五年年龄间隔中对 BMI 进行了 GWAS。然后，我们应用基因组结构方程模型来检验关于 BMI 遗传效应稳定性的竞争性假设。在 40 至 73 岁之间评估的 BMI 的 LDSR 遗传相关性都非常高，范围在 0.89 到 1.00 之间。基因组结构方程模型表明，每个年龄间隔的 BMI 的分子遗传方差不能用任何特定年龄的遗传影响或自回归过程的积累来解释。相反，一组共同的稳定遗传影响似乎为男性和女性从中年到老年早期的 BMI 全基因组变异提供了基础。
