Sedentary behaviour, muscle diseases, fractures: Mendelian randomisation study

This study investigated the associations between sedentary behaviour-specifically time spent driving, watching television, and using a computer-and the risk of musculoskeletal diseases and fractures using a Mendelian randomisation (MR) approach. A two-sample MR analysis was conducted based on data from the IEU GWAS database of the UK Biobank. Single-nucleotide polymorphisms significantly associated with sedentary behaviours, musculoskeletal disorders, and fractures were selected as instrumental variables after linkage disequilibrium testing, exclusion of potential confounders, and confirmation of instrument strength (F-statistics >10). Inverse variance weighting was used as the primary analytical method, with weighted median and MR-Egger regression as complementary analyses. Sensitivity analyses included Cochran's Q test, MR-Egger intercept testing, and leave-one-out analysis. Random- and fixed-effects models were applied to synthesise results across different sedentary behaviour domains. The MR analyses identified significant associations between television viewing and ankle fractures (P = 0.0182), television viewing and musculoskeletal and connective tissue diseases (P < 0.001), and heel bone mineral density and ankle fractures (P < 0.001). In contrast, computer use was negatively associated with musculoskeletal and connective tissue diseases (P = 0.0017), suggesting a potential protective effect that warrants further investigation. Overall, these findings indicate that sedentary behaviours have heterogeneous effects on musculoskeletal health. Television viewing was associated with an increased risk of ankle fractures and musculoskeletal diseases, whereas computer use showed an inverse association with musculoskeletal disorders. This study provides genetic evidence for the role of sedentary behaviour in the development of musculoskeletal and fracture-related diseases and may inform targeted prevention and intervention strategies. The study was registered in PROSPERO (CRD42024552384).