Type 2 diabetes mellitus increases risk of erectile dysfunction independent of obesity and dyslipidemia: A Mendelian randomization study

The causal effects of individual risk factors of metabolic syndrome on erectile dysfunction (ED) are still unclear.To evaluate the causal effect of risk factors of metabolic syndrome on ED through Mendelian randomization (MR).Data for risk factors were obtained from multiple databases with 173,082-757,601 individuals, and that for ED were collected from a genome-wide association study including 223,805 Europeans. We performed univariate MR analysis using inverse-variance weighted, MR-Egger, weighted-median, weighted mode methods and multivariable MR analysis to evaluate the total and direct causal effects.The univariable MR supported that type 2 diabetes mellitus (odds ratios [OR] = 1.14, 95% confidence intervals [CI]: 1.08-1.21, p < 0.001) and body mass index (BMI) (OR = 1.27, 95% CI: 1.12-1.44, p < 0.001) were associated with ED. After excluding the SNPs associated with BMI and other risk factors, the results of multivariable MR for T2D (OR = 1.15, 95% CI: 1.05-1.25, p = 0.001) remained consistent. However, the results of multivariable MR provided limited evidence for the causality between BMI and ED (OR = 1.06, 95% CI: 0.88-1.29, p = 0.532). For systolic blood pressure and lipid components (low-density lipoprotein, high-density lipoprotein and triglycerides), both univariable and multivariable MR failed to offer sufficient evidence to confirm their causal effect on ED.T2D showed a direct causal effect on ED independent of obesity and dyslipidemia.