Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore 119074, Singapore.
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
J Gerontol A Biol Sci Med Sci. 2024 Nov 1;79(11). doi: 10.1093/gerona/glae216.
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.
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.
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).
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.
成人身高与握力有关，握力是身体脆弱的替代标志物。然而，尚不确定这种关联是因果关系还是由于混杂偏倚所致。
我们通过多变量回归模型，使用在新加坡居住的中国前瞻性队列，在中介框架中使用身高多基因评分（PGS）和双样本 Mendelian 随机化方法评估了握力、成人身高和遗传决定的身高（PGS）之间的两两关联。我们还评估了与握力增加相关的身高相关基因的途径富集，以发现遗传决定的身高与握力之间关联的共同生物学机制。
调整中年体重和其他基线暴露（吸烟、教育和身体活动状况）后，PGS 与晚年握力呈正相关（p=1.2×10-9）。PGS 对握力的总效应中，约 66.4%通过成人身高间接介导（β间接效应=0.034，p 间接效应=1.4×10-40）。双样本 Mendelian 随机化评估显示，晚年身高增加与握力增加之间存在一致的因果关系（p 介于 6.6×10-4 和 3.9×10-18 之间），水平多效性效应不显著（pMR-Egger 截距=0.853）。与成人身高和握力增加均相关的基因途径分析显示，骨化和脂肪生成途径富集（padj 在 0.034 到 6.8×10-4 之间）。
该研究强调了晚年身高增加与握力增加之间可能存在因果关系，这可能是肌肉质量和力量在衰老过程中保持的相关生物学过程所解释的。
