Causal relationships between prostate cancer and six psychiatri c disorders: A two-sample Mendelian randomization study

Abstract

Abstract Background Prostate cancer (PCa) diagnosis and survival have increased significantly with the development and use of screening techniques. The PCa patient population has a higher risk of psychiatric health issues than the overall population. It has not been demonstrated that PCa and psychiatric disorders are related genetically. Methods The current investigation employed a two-sample bidirectional Mendelian randomization design, incorporating a genome-wide association study (GWAS) to systematically screen for genetic instrumental variables related to PCa and six psychiatric disorders, namely major depressive disorder, Alzheimer's disease, insomnia, bipolar disorder, anxiety disorders, and attention deficit hyperactivity disorder. The primary method for assessing causal associations between the two disorders was Inverse Variance Weighting (IVW), supplemented by additional analyses utilizing the MR-Egger and Weighted Median methods, as well as sensitivity analyses to confirm their dependability. In order to confirm the good outcomes of the MR study, we also chose another set of prostate cancer GWAS data from the same pedigree population. To make the results more reliable, we conducted a meta-analysis. Results Genetically predicted PCa was associated with higher odds of BD (OR = 1.06,95%, CI = 1.02–1.10, PIVW=0.0055) and lower odds of MDD (OR = 0.97,95% CI = 0.95-1.00, PIVW=0.0261) in the forward MR analysis from PCa to psychiatric disorders. Reverse MR analysis showed that genetically expected BD (OR = 1.08, 95% CI = 1.01–1.10, PIVW=0.0303) was associated with higher odds of PCa. No causal association was found between the other four psychiatric disorders and PCa in the two-way analysis. Heterogeneity and horizontal pleiotropy were not observed in all results, and the robustness of the results was demonstrated by the leave-one-out results. MR analyses performed with the optional additional PCa GWAS were directionally consistent with the main analysis, confirming a causal association between MDD and PCa, but greater heterogeneity was observed in the bidirectional causal association of BD. Conclusions Our research suggested a potential genetic causal relationship between BD, MDD, and PCa. There was no genetically based causal relationship found between PCa, ADHD, sleeplessness, anxiety disorders, and AD. The results of this study have significant ramifications for the future screening and management of PCa patients, particularly with regard to the inclusion of psychological therapies and support.