Herranen Päivi, Waller Katja, Joensuu Laura, Palviainen Teemu, Laakkonen Eija K, Kaprio Jaakko, Sillanpää Elina
Faculty of Sport and Health Sciences, Gerontology Research Center University of Jyväskylä Finland.
Institute for Molecular Medicine Finland, HiLife Helsinki Finland.
J Am Heart Assoc. 2025 May 6;14(9):e036941. doi: 10.1161/JAHA.124.036941. Epub 2025 Apr 16.
Low muscle strength predicts premature mortality. We determined whether genetic liability to muscle strength is associated with mortality and whether this association is influenced by long-term leisure-time physical activity (LTPA).
We estimated the effects of a polygenic score for handgrip strength (PGS HGS) on all-cause and cardiovascular disease (CVD) mortality risk in the older Finnish Twin Cohort (N=8815, 53% women). LTPA was assessed longitudinally using validated questionnaires. During the 16.9-year median follow-up (143 723 person-years), 2896 deaths occurred, of which 1089 were attributable to CVD. We found a significant interaction between sex and PGS HGS (=0.016) in relation to all-cause mortality. In men, 1-SD increase in the PGS HGS was associated with a decreased risk of all-cause (hazard ratio [HR], 0.93 [95% CI, 0.89-0.98]) and CVD mortality (HR, 0.88 [95% CI, 0.81-0.96]), but was not statistically significantly associated with mortality in women (HR, 1.01 [95% CI, 0.96-1.07]; and HR, 0.96 [95% CI, 0.87-1.05], respectively). In men, associations remained after adjusting for LTPA and persisted for CVD mortality (HR, 0.85 [95% CI, 0.76-0.96]), even after accounting for other lifestyle covariates. This remained statistically significant even when non-CVD death was accounted for as a competing risk event. No PGS HGS×LTPA interactions were found. The predictive area under the curve estimates for PGS HGS alone were limited (0.53-0.64) but comparable to that of several lifestyle factors.
Higher PGS HGS was associated with a decreased risk of CVD mortality in men. Long-term LTPA in adulthood did not potentiate this association.
肌肉力量低预示着过早死亡。我们确定了肌肉力量的遗传易感性是否与死亡率相关，以及这种关联是否受长期休闲体育活动（LTPA）的影响。
我们评估了握力多基因评分（PGS HGS）对芬兰老年双胞胎队列（N = 8815，53%为女性）全因死亡率和心血管疾病（CVD）死亡风险的影响。使用经过验证的问卷纵向评估LTPA。在16.9年的中位随访期（143723人年）内，发生了2896例死亡，其中1089例归因于CVD。我们发现，在全因死亡率方面，性别与PGS HGS之间存在显著交互作用（P = 0.016）。在男性中，PGS HGS增加1个标准差与全因死亡风险降低相关（风险比[HR]，0.93[95%CI，0.89 - 0.98]）以及CVD死亡风险降低相关（HR，0.88[95%CI，0.81 - 0.96]），但在女性中与死亡率无统计学显著关联（HR，1.01[95%CI，0.96 - 1.07]；以及HR，0.96[95%CI，0.87 - 1.05]）。在男性中，调整LTPA后关联仍然存在，并且即使在考虑其他生活方式协变量后，CVD死亡率的关联仍然持续（HR，0.85[95%CI，0.76 - 0.96]）。即使将非CVD死亡作为竞争风险事件考虑，这一结果仍具有统计学显著性。未发现PGS HGS×LTPA交互作用。单独的PGS HGS的曲线下预测面积估计值有限（0.53 - 0.64），但与几个生活方式因素相当。
较高的PGS HGS与男性CVD死亡风险降低相关。成年期长期的LTPA并未增强这种关联。
