Causal association between erectile dysfunction and the risk of myocardial infarction:A two-sample bidirectional Mendelian randomization study
10.13263/j.cnki.nja.2025.08.002
- VernacularTitle:勃起功能障碍与心肌梗死风险的因果关系:基于两样本双向孟德尔随机化研究
- Author:
Ye-tong ZHANG
1
;
Xue-fei DING
;
Yu-xuan SHANG
;
Shang WU
Author Information
1. 大连医科大学扬州临床医学院,江苏扬州 225001
- Publication Type:Journal Article
- Keywords:
erectile dysfunction;
myocardial infarction;
causality;
Mendelian randomization study
- 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 Gene-card 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 re-lationship between ED and MI.In multivariate Mendelian randomization analysis,after excluding confounding factors(excluding tri-glycerides and high-density lipoprotein),the P-value remained less than 0.05,and the OR ranged from 1.000 1 to 1.000 7,indica-ting 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 spontaneous-ly 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.
