The aim of this study was to use Mendelian randomization (MR) method to deeply explore the possible causal association between depression and rotator cuff injury. Using pooled data from genome-wide association studies covering large-scale populations, independent genetic loci associated with depression and rotator cuff injuries and showing significant genetic associations in populations of European ancestry were carefully selected as study instrumental variables. The potential causal effect of depression on rotator cuff injury was systematically assessed by implementing 3 MR analysis strategies: MR-Egger regression, weighted median, and inverse variance weighting. Heterogeneity and multiplicity tests were further incorporated into the study, supplemented by a “leave-one-out” sensitivity analysis to ensure the reliability and robustness of the results. The combined results of this inverse variance weighting analysis (OR 0.72, 95% confidence interval = 0.41 to 1.27, P -value = .259) indicated that there was no significant causal association between depression and rotator cuff injury. In addition, no significant heterogeneity or pleiotropy was detected by a comprehensive test, and further sensitivity analyses confirmed the stability of the findings. Using 2-sample MR analysis, the present study provided an in-depth analysis of the genetic data, revealing a lack of clear causal evidence between depression and rotator cuff injury. Given the limitations of the current data, future studies should consider the inclusion of larger samples with the aim of exploring potential causal links with greater precision.
Hu et al. (2026) studied this question.