Causal association between erectile dysfunction and the risk of myocardial infarction: A two-sample bidirectional Mendelian randomization study.
- Author:
Ye-Tong ZHANG
1
;
Xue-Fei DING
2
;
Yu-Xuan SHANG
3
;
Shang WU
2
Author Information
1. The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou, Jiangsu 225001, China.
2. Department of Urology, Northern Jiangsu People's Hospital Afflicted to Yangzhou University Yangzhou, Yangzhou, Jiangsu 225001, China.
3. Department of Plastic Surgery, The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang 311201, China.
- Publication Type:Journal Article
- Keywords:
erectile dysfunction;
myocardial infarction;
causality;
Mendelian randomization study
- MeSH:
Humans;
Male;
Mendelian Randomization Analysis;
Myocardial Infarction/genetics*;
Erectile Dysfunction/complications*;
Risk Factors;
Genome-Wide Association Study;
Molecular Docking Simulation;
Polymorphism, Single Nucleotide
- From:
National Journal of Andrology
2025;31(8):684-691
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To evaluate the association between erectile dysfunction (ED) and myocardial infarction (MI) using two sample Mendelian randomization.
METHODS:A Mendelian randomization study was conducted using comprehensive data on ED and MI from extensive genome-wide association data. Using inverse variance weighted analysis for causal relationships, and correct for confounding factors using multivariate Mendelian randomization, the potential mediating effects were evaluated as well. Based on Genecard data, the genes related to ED and MI were identified. Molecular docking was used to reveal spontaneously bound drug molecules.
RESULTS:Our study found that exposure to ED was a risk factor for MI (OR: 1.001 0, 95% CI: 1.000 2－1.001 8, P=0.017 7), which also held true in the validation dataset (OR: 1.028 5, 95% CI: 1.005 0－1.052 6, P=0.017 2). No statistically significant heterogeneity or horizontal pleiotropy was found. The results of reverse Mendelian randomization analysis showed any reverse causal relationship between ED and MI. In multivariate Mendelian randomization analysis, after excluding confounding factors (excluding triglycerides and high-density lipoprotein), the P-value remained less than 0.05, and the OR ranged from 1.000 1 to 1.000 7, indicating that ED was still a risk factor for MI. In the mediation analysis, it was found that the current mediation ratio of smoking to MI was 13.06%. In summary-data-based mendelian randomization analysis, it was found that the gene PTPN11 was a common target gene for MI and ED (OR=0.990, P<0.001). Subsequent molecular docking with sildenafil, clopidogrel, and dapoxetine could spontaneously bind to the PTPN11 gene receptor.
CONCLUSION:There is a causal relationship between ED and MI, with smoking as a potential mediating factor, and the gene PTPN11 being a co-target gene.
