Evaluation of bi-directional causal association between periodontal disease and erectile dysfunction: a two-sample Mendelian randomization study.

ABSTRACT

BACKGROUND: The association between periodontal disease (PD) and erectile dysfunction (ED) has been well-documented in observational studies. However, observational studies are vulnerable to reverse causality and confounding factors, making the inference of causal-effect relationships challenging. Contrary to the current belief, Mendelian randomization (MR) can be applied to comprehensively assess the bi-directional causal effects between PD and ED. METHODS: A two-sample MR analysis was performed using pooled statistics from genome-wide association studies involving European populations with PD (12,289 patients with PD and 22,326 controls) and ED (6,175 patients with clinically diagnosed ED and 217,630 controls). In this MR analysis, three methods--the inverse-variance weighted (IVW) average, weighted median, and MR-Egger regression methods--were used to evaluate the causal relationships between PD and ED. RESULTS: According to the IVW analysis results, genetically predicted PD did not have a causal effect on ED (odds ratio 1.07, 95% confidence interval 0.96-1.20, p = 0.22). Furthermore, there was no clear indication of a significant causal effect of ED on PD in the reverse MR analysis (odds ratio 0.98, 95% confidence interval 0.90-1.08, p = 0.74). The results of the MR-Egger regression and weighted median methods were consistent with those of the IVW method. Based on the sensitivity analysis results, a major bias from genetic pleiotropy was unlikely to distort the causal estimates. CONCLUSION: The present study does not support a causal effect between PD and ED. CLINICAL RELEVANCE From the perspective of genetics, PD does not appear to be a risk factor for the development of ED.