Abstract
BACKGROUND: Mental disorders (MDs) are associated with prostate cancer (PCa) outcomes, but the results reported by different studies are inconsistent. Our aim was to explore the causal relationship between 10 MDs and PCa using bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analysis. METHODS: Our study was based on summary data from genome-wide association studies (GWAS) of PCa and 10 major MDs in the European population. The genetic locus data used in the analysis included variants associated with PCa and the 10 MDs. Causal estimates were calculated using the inverse-variance weighted (IVW) method, and sensitivity MR techniques, including Cochran's Q test, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), were employed to evaluate potential horizontal pleiotropy and heterogeneity. All statistical analyses were conducted using R software. RESULTS: Our study did not find a causal relationship between PCa and the 10 MDs. In reverse MR analysis, a causal association between insomnia and PCa was found only for insomnia, which reduced PCa risk (odds ratio [OR], 0.9706; 95% confidence interval [CI], 0.9468-0.9951; p = 0.0188). However, after MVMR adjustment for habits (cigarette smoking, alcohol intake, coffee intake, and tea intake), this causal relationship no longer existed (OR, 1.011; 95% CI, 0.932-1.096; p = 0.795). CONCLUSION: This study demonstrated a negative correlation between insomnia and PCa from a genetic perspective. However, such results may be mediated by lifestyle habits and therefore need to be interpreted with caution.