J Sports Sci. 2026 May 31:1-12. doi: 10.1080/02640414.2026.2673237. Online ahead of print.
ABSTRACT
The shared genetic architecture linking physical activity, sedentary behavior, and osteoporosis risk remains unclear. We investigated the genetic basis, pleiotropic effects, and causal relationships between moderate-to-vigorous physical activity (MVPA), leisure screen time (LST), and heel estimated bone mineral density (eBMD). Leveraging summary statistics from genome-wide association studies of European individuals (MVPA: N = 606,820; LST: N = 526,725; eBMD: N = 426,824), we conducted a genome-wide cross-trait analysis. A significant global genetic correlation was observed for MVPA and eBMD ( = 0.13, P = 7.97 × 10-11), but not for LST and eBMD ( = 0.02, P = 0.34). Two specific genomic regions showed evidence of local genetic correlation. Cross-trait meta-analysis identified 90 pleiotropic loci, of which 20 were novel. Transcriptome-wide association studies revealed 42 shared genes. Mendelian randomization suggested a causal relationship between genetically predicted MVPA and eBMD (beta = 0.07, 95%CIs = 0.01-0.14, P = 0.03), but not for LST (beta = 0.01, 95%CIs = 0.04-0.05, P = 0.81). Our findings demonstrate a shared genetic basis and pleiotropic effects between MVPA and eBMD, highlighting their intrinsic link and supporting MVPA’s role in osteoporosis prevention.
PMID:42218761 | DOI:10.1080/02640414.2026.2673237
