Genetic Support for the Increased Risk of Erectile Dysfunction in Prostate Cancer: A Bidirectional Mendelian Randomization Study

Abstract

Epidemiological evidence has shown that prostate cancer (PCa) and erectile dysfunction (ED) are factors of increased mutual risk. However, the causal relationship between PCa and ED remains elusive due to the methodological limitations of traditional observational studies. Thus, we performed a bidirectional two-sample Mendelian randomization (MR) study to investigate the causal relationship between PCa and ED. We used genome-wide association studies of PCa and ED to obtain single-nucleotide polymorphisms (SNPs). The inverse variance weighted method was used as the primary analysis tool to obtain causal effects, and we adopted an MR–Egger, weighted median, simple, and weighted model for the complementary analysis. Using univariable MR, genetic evidence indicated that PCa has a causal genetic liability effect on ED using both the explored and the replicate dataset (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.06–1.17, p < 0.001 and OR 1.62, 95% CI 1.48–1.78, p < 0.001, respectively). Furthermore, the combined result of the meta-analysis (inverse variance weighting [IVW]: OR 1.17, 95% CI 1.12–1.23, p < 0.001). In the reverse direction, ED showed no genetic liability on PCa (OR 1.01, 95% CI 0.96–1.06, p = 0.759 and OR 1.17, 95% CI: 0.93–1.48, p = 0.172). In multivariate MR, the association remained after eliminating the confounders to estimate the direct causal effect of PCa on ED (all p < 0.001). This study provided genetic evidence suggesting that PCa has a causal effect on increased ED risk, but ED showed no such effect on PCa.