A 2-sample Mendelian randomization study investigating ever smoking as a risk factor for rotator cuff injury

This study aimed to investigate the potential causal relationship between smoking and the risk of developing rotator cuff injury using Mendelian randomization (MR) techniques. Methods: Genetic variants significantly and independently associated with ever smoking and rotator cuff injury were identified from individuals of European ancestry using summary statistics from large-scale genome-wide association studies. These variants served as instrumental variables for MR analysis. Three complementary MR approaches were applied: inverse variance weighting, MR-Egger regression, and the weighted median method. Heterogeneity and horizontal pleiotropy were assessed to validate the instrumental variables. A leave-one-out sensitivity analysis was conducted to test the robustness of the findings. Results: The inverse variance weighting method demonstrated a significant causal association between ever smoking and rotator cuff injury (OR = 3.29, 95% CI: 1.41–7.71, P = .006). The weighted median method yielded similar results (OR = 2.95, 95% CI: 1.04–8.40, P = .043). However, the MR-Egger regression did not show a statistically significant association (OR = 2.15, 95% CI: 0.41–11.28, P = .359), indicating potential model sensitivity. Conclusion: Our findings provide suggestive – but not definitive – evidence for a causal relationship between ever smoking and increased risk of rotator cuff injury. These results highlight the need for further studies using larger datasets and complementary analytical strategies to validate the observed association.