Background Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias. Methods We evaluated pairwise associations among handgrip strength, adult height, and genetically determined height (using a polygenic score [PGS] for height in a mediation framework and a 2-sample Mendelian randomization approach) by means of a multivariable regression model using a prospective cohort of Chinese living in Singapore. We additionally evaluated pathway enrichments of height-related genes in relation to increased handgrip strength to discover common biological mechanisms underlying associations of genetically determined height with handgrip strength. Results Height PGS exhibited a positive association with handgrip strength at late life after adjusting for midlife body weight and other baseline exposures (cigarette smoking, education, and physical activity status, p = 1.2 × 10−9). Approximately 66.4% of the total effect of height PGS on handgrip strength was mediated through adult height (βindirect-effect = 0.034, pindirect-effect = 1.4 × 10−40). Two-sample Mendelian randomization evaluations showed a consistent causal relationship between increased height and increased handgrip strength in late life (p between 6.6 × 10−4 and 3.9 × 10−18), with insignificant horizontal pleiotropic effects (pMR-Egger intercept = 0.853). Pathway analyses of genes related to both increased adult height and handgrip strength revealed enrichment in ossification and adipogenesis pathways (padj between .034 and 6.8 × 10−4). Conclusions The study highlights a potentially causal effect between increased adult height and increased handgrip strength in late life, which may be explained by related biological processes underlying the preservation of muscle mass and strength in aging.

中文翻译：

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成人身高对晚年握力的因果效应：新加坡华人健康研究


背景 成人身高与握力有关，握力是身体虚弱的替代标志。然而，尚不确定这种关联是因果关系还是由于混杂偏倚。方法 我们通过使用居住在新加坡的华人前瞻性队列的多变量回归模型，评估了握力、成人身高和遗传确定身高之间的成对关联 （在中介框架中使用身高多基因评分 [PGS] 和 2 样本孟德尔随机化方法）。我们还评估了与握力增加相关的身高相关基因的通路富集，以发现遗传决定的身高与握力关联的常见生物学机制。结果在调整中年体重和其他基线暴露后，身高 PGS 与晚年握力呈正相关 （吸烟、教育和身体活动状况，p = 1.2 × 10-9）。身高 PGS 对握力的总影响中约 66.4% 是通过成人身高介导的 （β间接效应 = 0.034，针×直接效应 = 1.4 10-40）。双样本孟德尔随机化评估显示，晚年身高增加和握力增加之间存在一致的因果关系 （p 在 6.6 × 10-4 和 3.9 之间 × 10-18），水平多效性效应不显著 （pMR-Egger 截距 = 0.853）。与成年身高增加和握力相关的基因通路分析显示骨化和脂肪生成通路的富集 （padj 在 .034 和 6.8 之间× 10-4）。 结论 该研究强调了成年身高增加与晚年握力增加之间的潜在因果关系，这可能由衰老中保持肌肉质量和力量的相关生物过程来解释。