Causal association between benign anorectal disorders and mental disorders: A Mendelian randomization study.

Increasing evidence suggests a strong association between benign anorectal diseases and mental health; however, the causal relationship between them remains unclear. This study aims to investigate the causal effects of 4 common mental disorders on 3 common benign anorectal disorders using Mendelian randomization. We performed 2-sample MR analysis using summary data from genome-wide association studies. Three methods were applied: inverse variance weighting, MR-Egger regression, and weighted median. Sensitivity analyses were conducted using MR-Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, Cochran's Q test, and leave-one-out analysis. Additionally, multivariable MR was used to assess the direct and independent causal effects of mental disorders on benign anorectal disorders, adjusting for potential confounders. Reverse MR analysis was conducted to validate the direction of causality. Finally, LDSC was employed to assess the genetic correlation between the conditions. Two-sample MR analysis revealed that depression has a significant effect on hemorrhoids (P: .0018, odds ratio [OR]: 1.0082) and a potential effect on anorectal abscesses (P: .0208, OR: 2.5448). Schizophrenia showed a potential effect on hemorrhoids (P: .0117, OR: 1.0006). Sensitivity analyses revealed no significant heterogeneity or horizontal pleiotropy, suggesting stable results. Reverse causality was not observed. Multivariable MR analysis confirmed that, after adjusting for the mutual effects of schizophrenia and depression, the causal effects remained significant. After controlling for body mass index and smoking status, the causal relationship remains significant. LDSC analysis demonstrated significant genetic correlations between depression and both hemorrhoids and anorectal abscesses. This study provides evidence that depression has an impact on hemorrhoids and anorectal abscesses, schizophrenia affects hemorrhoids, and depression has a significant effect on hemorrhoids.