Effects of physical activity and sedentary behavior on cardiovascular disease and respiratory diseases

Cardiovascular disease (CVD) and respiratory disorders (RD) are major causes of premature death. Whether moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB) causally affect these outcomes, and through which molecular pathways, remains unclear.

We employed a multi-method Mendelian randomization (MR) framework to assess the causal effects of MVPA, sedentary breaks at work (SBAW), leisure screen time (LST), and sedentary commuting (SC) on CVD and RD. Complementary transcriptomic analyses of GEO datasets identified differentially expressed genes (DEGs).

After Bonferroni correction, genetically predicted MVPA and SBAW were protective (OR = 0.747, 95 % CI: 0.637-0.876, p = 3 × 10⁻⁴; OR = 0.783, 95 % CI: 0.700-0.876, p = 2.03 × 10⁻⁵), and LST was harmful for CVD (OR = 1.172, 95 % CI: 1.023-1.341, p = 0.022). Parallel associations were observed for RD (MVPA: OR = 0.800, 95 % CI: 0.669-0.957, p = 0.015; SBAW: OR = 0.838, 95 % CI: 0.746-0.942, p = 0.003; LST: OR = 1.153, 95 % CI: 1.028-1.293, p = 0.015). Multivariable MR further confirmed the causal effects of physical activity on both outcomes (OR = 0.770, p = 6.14 × 10⁻⁵; OR = 0.894, p = 0.021). Bioinformatics analyses identified 713 DEGs in CVD and 602 in RD; PLA2G2A and C3 emerged as key CVD genes, and CCL5 for RD.

These findings suggest that individual differences in MVPA and SB may influence cardiopulmonary health. The identification of shared molecular signatures suggests potential mechanisms and possible biomarkers, informing precision prevention strategies that emphasize "move more, sit less."