Potential causal association between leisure sedentary behaviors, physical activity and musculoskeletal health: A Mendelian randomization study

Increasing evidence shows that leisure sedentary behaviors (LSB) and physical activity (PA) are associated with various musculoskeletal disorders. However, the causality between LSB/PA and musculoskeletal health remained unknown. In this study, we aimed to evaluate the causal relationships between LSB/PA and lower back pain (LBP), intervertebral disc disorder (IVDD), rheumatoid arthritis (RA), and bone mineral density (BMD) by using a two-sample Mendelian randomization method. The exposure data were obtained from large-scale genome-wide association studies (GWAS), including the PA dataset (self-reported PA, n = 377,234; accelerometer-assessed PA, n = 91,084) and LSB dataset (n = 422,218). The outcome data were derived from the FinnGen LBP dataset (n = 248,528), FinnGen IVDD dataset (n = 256,896), BMD GWAS dataset (n = 56,284), and RA GWAS dataset (n = 58,284). The causal relationships were estimated with inverse variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analyses were performed with Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to estimate the robustness of our findings. Genetically predicted leisure television watching increased the risk of LBP (OR = 1.68, 95% CI 1.41 to 2.01; P = 8.23×10-9) and IVDD (OR = 1.62, 95% CI 1.37 to 1.91; P = 2.13 × 10-8). In addition, this study revealed a potential causal relationship between computer use and a reduced risk of IVDD (OR = 0.60, 95% CI 0.42 to 0.86; P = 0.005) and RA (OR = 0.28, 95% CI 0.13 to 0.60; P = 0.001). Our results suggest that leisure television watching is a risk factor for LBP and IVDD, whereas leisure computer use may act as a protective factor against IVDD and RA. These findings emphasized the importance of distinguishing between different sedentary behaviors in musculoskeletal disease studies.