Causal Association between Erectile Dysfunction with Urate Levels and Gout: A Two-Sample Mendelian Randomization Study

A plethora of studies have demonstrated that the level of uric acid (UA) and gout are the risk factors for erectile dysfunction (ED). However, the causal effect of UA level and gout on ED is still unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between ED and UA levels as well as gout. We performed a bidirectional MR analysis using summary statistics from genome-wide association studies (GWAS) to investigate the causal association between ED and UA levels as well as gout. We meticulously selected single nucleotide polymorphisms (SNPs) based on rigorous criteria as instrumental variables. Four two-sample MR analysis methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode, were applied in our study. Furthermore, several sensitivity analyses including Cochrane's Q-test, MR-Egger intercept test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) global test, and leave-one-out analysis were performed to assess heterogeneity, horizontal pleiotropy, and stability. The study included one dataset related to UA levels (GWAS meta-analysis conducted by Tin et al.), two datasets related to gout (ukb-b-12765 and finn-R9-M13_GOUT), and one dataset related to ED (GWAS meta-analysis conducted by Bovijn et al.). MR results of the IVW method indicated that UA levels and gout were not causally associated with ED in three UA levels/gout-related datasets (IVW, odds ratios (OR): 0.99, 95% confidence interval (CI): 0.92-1.07, p = 0.834; 3.20, 0.17-61.69, 0.441; 1.03, 0.97-1.09, 0.372, respectively). The reverse MR revealed no evidence of a causal effect of ED on UA levels or gout according to the IVW method (OR: 0.99, 95% CI: 0.96-1.02, p: 0.568; 1.00, 1.00-1.00, 0.555; 0.97, 0.89-1.05, 0.425, respectively). The results of other MR analysis methods were consistent with IVW. Furthermore, sensitivity analysis suggested that the results were robust, with no pleiotropy or heterogeneity detected. Our MR study supports no bidirectional causal effect of UA level or gout on ED.