Abstract
BACKGROUND: Previous epidemiological investigations and related research efforts consistently have outlined an observable association between anxiety disorders and adhesive capsulitis (AC). However, the intricate nature of the causal connection between these entities has yet to be fully clarified. Therefore, this investigative study aims to thoroughly examine and delineate the causal interrelationship between anxiety disorders and AC using a bidirectional, two-sample Mendelian randomization (MR) approach. METHODS: To pursue this inquiry, datasets related to anxiety disorders and AC were meticulously obtained from a publicly accessible genomewide association study. Instrumental variables, in the form of single nucleotide polymorphisms, were subsequently identified, undergoing a rigorous screening process that included intensity adjustment and the amelioration of linkage disequilibrium. The primary analytical tool for scrutinizing causal ramifications was the inverse variance weighting (IVW) methodology, complemented by supplementary analytical techniques such as weighted median, MR-Egger, simple mode, and weighted mode. Additionally, evaluations of heterogeneity and pleiotropy were meticulously conducted. Heterogeneity was assessed using Cochran's Q-test in conjunction with the IVW and MR-Egger methods, while pleiotropy was appraised through the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was undertaken to enhance the reliability of our findings. Finally, AC was utilized to infer reverse causality concerning the risk of anxiety disorders. RESULTS: The random effects IVW analysis results yielded statistical significance (P = 9.362 × 10(-6)), demonstrating a causal link between anxiety disorders and elevated susceptibility to AC, reflected in an odds ratio of 1.267 (95% confidence interval: 1.141-1.407). Conversely, the inverse MR analysis predominantly produced null findings. Furthermore, sensitivity analyses underscored the robustness of our conclusions. CONCLUSION: In summary, our meticulously conducted study unequivocally supports the presence of a causal connection between anxiety disorders and an increased propensity for AC. Unfortunately, the reverse MR analysis failed to provide compelling evidence indicative of a reciprocal genetic causative relationship between AC and anxiety disorders.