Background: Observational studies have indicated a high prevalence of erectile dysfunction (ED) among patients with inflammatory bowel disease (IBD), but a definitive causal relationship remains unestablished.
Aim: The primary aim of this study was to assess the potential causal relationship between IBD and ED using Mendelian randomization (MR) analysis.
Methods: We obtained statistical data for 2 subtypes of IBD, ulcerative colitis (UC) and Crohn's disease (CD), as well as for ED, from publicly available genome-wide association studies (GWASs). Subsequently, a 2-sample MR analysis was conducted using these datasets. The primary MR analysis utilized the inverse variance-weighted (IVW) method, complemented by secondary analyses employing MR-Egger and weighted median methods. Furthermore, we assessed heterogeneity using Cochran's Q test and evaluated pleiotropy with the MR-Egger intercept test. To identify potential influential single nucleotide polymorphisms, we employed a leave-one-out analysis. Additionally, outliers were identified using the MR-PRESSO method.
Outcomes: The study outcomes encompassed results from 3 MR analyses, namely IVW, MR-Egger, and weighted median, along with sensitivity analyses involving Cochran's Q test, the MR-Egger intercept test, leave-one-out analysis, and the MR-PRESSO method.
Results: There was no causal effect of UC and CD on ED in the MR analysis (IVW P > .05). Results of complementary methods were consistent with those of the IVW method. The results of sensitivity analyses supported our conclusion, and no directional pleiotropy was found.
Clinical implications: Genetically, despite the absence of a causal link between IBD and ED according to MR analysis, we must emphasize the elevated ED prevalence among IBD patients in observational studies, with particular consideration for the influence of negative emotions on erectile function.
Strengths & limitations: This study is the inaugural application of a 2-sample MR analysis using extensive GWAS datasets to evaluate the causal relationship between IBD and ED, effectively mitigating biases stemming from confounding factors and reverse causality often present in observational studies. Nevertheless, it is imperative to exercise caution when drawing conclusions due to inherent limitations in GWAS data, encompassing factors like samples overlap, gender categorization, population ancestry, and the persistent ambiguity surrounding the precise functionality of specific single nucleotide polymorphisms.
Conclusions: MR analysis did not provide genetic-level evidence supporting a direct causal relationship between IBD (UC and CD) and ED.
Keywords: Crohn's disease; Mendelian randomization; erectile dysfunction; inflammatory bowel disease; ulcerative colitis.
© Published by Oxford University Press on behalf of The International Society of Sexual Medicine 2024.