Galimberti Marco, Levey Daniel F, Deak Joseph D, Adhikari Keyrun, Overstreet Cassie, Gupta Priya, Nitin Rachana, Zhou Hang, Lake Nicole J, Harrington Kelly M, Djousse Luc, Davis Lea K, Gaziano J Michael, Stein Murray B, Gelernter Joel
Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Nat Genet. 2025 Jul 21. doi: 10.1038/s41588-025-02260-9.
Physical activity (PA) is one of the most fundamental traits in the animal kingdom, has pervasive health benefits, and is genetically influenced. Using data from the Million Veteran Program, we conducted genetic analyses of leisure, work and home-time PA. For leisure, we included 189,812 individuals of European ancestry (SNP-based heritability (h) = 0.083 ± 0.005), 27,044 of African ancestry (h = 0.034 ± 0.017) and 10,263 of Latin American ancestry (h = 0.083 ± 0.036) in a cross-ancestry meta-analysis with UK Biobank data, identifying 70 lead variants. Leisure-time PA was genetically distinct from PA at home or work, with the latter two showing less health benefit with respect to health outcomes and lifespan. Mendelian randomization analyses showed a protective role of leisure-time PA against COVID-19 hospitalization (β = -0.067 ± 0.016; P = 2.8 × 10), and with other traits including cardiovascular and respiratory system diseases, metabolic traits and aging. These findings provide new insights into the biology of PA, showing specific causal health benefits of leisure-time PA.
身体活动（PA）是动物界最基本的特征之一，具有广泛的健康益处，且受基因影响。利用来自百万退伍军人计划的数据，我们对休闲、工作和居家时间的身体活动进行了基因分析。对于休闲活动，我们在一项与英国生物银行数据的跨血统荟萃分析中纳入了189812名欧洲血统个体（基于单核苷酸多态性的遗传力（h）=0.083±0.005）、27044名非洲血统个体（h=0.034±0.017）和10263名拉丁美洲血统个体（h=0.083±0.036），确定了70个主要变异。休闲时间的身体活动在基因上与在家或工作时的身体活动不同，后两者在健康结果和寿命方面显示出较少的健康益处。孟德尔随机化分析表明，休闲时间的身体活动对COVID-19住院有保护作用（β=-0.067±0.016；P=2.8×10），并与包括心血管和呼吸系统疾病、代谢特征及衰老在内的其他特征有关。这些发现为身体活动的生物学提供了新的见解，显示了休闲时间身体活动特定的因果健康益处。
