Causal effects of sedentary behavior and physical activity on the risk of musculoskeletal disorders: Evidence from Mendelian randomization analysis

Previous studies have noted the associations of sedentary behavior and physical activity with several musculoskeletal disorders (MSDs), yet the causality of these relationships remains unclear. In this study, we probed into the causal associations between sedentary behavior, physical activity, and the risk of 13 MSDs through Mendelian randomization (MR) analysis. We obtained summary statistics for leisure screen time (LST) and moderate-to-vigorous intensity physical activity (MVPA) from genome-wide association studies (GWAS) for 2-sample univariable MR analysis. The linkage disequilibrium score regression (LDSC) was used for genetic correlation analysis. Multivariable MR analysis was conducted on LST and MVPA to adjust for one another. Furthermore, we performed mediation analysis to reveal the potential mediating effect of body mass index (BMI). After Benjamini-Hochberg correction, LST was significantly associated with an increased risk of 8 MSDs, including spinal stenosis, spondylolisthesis, low back pain, cervicobrachial syndrome, rotator cuff syndrome, meniscus derangement, lateral epicondylitis, and gout. All these MSDs had positive genetic correlations with LST. There was no causal effect of MVPA on MSDs. However, after adjusting for LST, the association between MVPA and scoliosis became significant; the associations between LST and all 8 MSDs remained after adjusting for MVPA. Two-step mediation analysis found that BMI mediated all the associations between LST and MSDs. Our study provides genetic evidence supporting that sedentary behavior is a causal risk factor for most MSDs independent of physical activity. These findings offer valuable insights for the development of evidence-based prevention strategies and interventions targeting MSDs.