Causal associations between erectile dysfunction and high blood pressure, negative psychology: a Mendelian randomization study

Abstract

Erectile dysfunction (ED) has been closely associated with both high blood pressure (HBP) and psychological traits, but the causal relationship between them remains unclear. Herein, we aimed to identify the causal risk factors for ED. We conducted univariable and multivariable Mendelian randomization (MR) analyses using genetic variants associated with metabolic syndrome and psychology traits at the genome-wide significance (p < 5 × 10−8) level obtained from corresponding genome-wide association studies. We used summary-level statistical data for ED from the European Bioinformatics Institute (EBI) database of complete Genome-Wide Association Studies (GWAS) summary data. We also conducted reverse causality and performed power calculations for MR. Our results showed that HBP was associated with increased odds of ED (odds ratio (OR) = 1.66 (95% confidence interval (CI), 1.13–2.45), a p-value for the inverse variance-weighted method (PIVW) = 1.06 × 10−2, Power = 100%), as were myocardial infarction (OR = 1.09 (95% CI, 1.02–1.17), PIVW = 1.18 × 10−2, Power = 56%) and ischemic stroke (OR = 1.21 (95% CI, 1.02–1.43), PIVW = 2.87 × 10−2, Power = 10%). In terms of psychological traits, irritable mood (OR = 1.86 (95% CI, 1.14–3.02), PIVW = 1.30 × 10−2, Power = 96%) and neuroticism (OR = 1.36 (95% CI, 1.04–1.79), PIVW = 2.66 × 10−2, Power = 80%) were associated with increased odds of ED. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) showed no evidence of pleiotropic bias, and sensitivity analyses confirmed the robustness of our results. We have established a causal link between HBP and ED, and we have also found evidence suggesting a causal relationship between irritable mood and ED.

Keywords

• erectile dysfunction
• high blood pressure
• negative psychology
• single-nucleotide polymorphisms
• mendelian randomization