Exploring The Impact Factors Of Erectile Dysfunction Based On NHANES And Mendelian Randomization

Background: Erectile dysfunction(ED)is a common sexual dysfunction in clinic,which mainly affects the men who are over 40.ED is mainly manifested as the inability to achieve or maintain a sufficient penile erection for successful sexual intercourse.As a multi-dimensional disorder,ED can be caused by any abnormal system that plays a role in the normal erection process.In the past,ED was often attributed to a psychological disorder,but a growing number of observational studies suggested otherwise: ED could be a kind of organic disease which was associated with and a variety of life factors.However,these conclusions are susceptible to unobserved confounding factors,and the resulting correlations do not simply equate to causation.Therefore,this study used the clinical database of National Health and Nutrition Examination Survey(NHANES)to explore the factors affecting ED.Further the Mendelian randomization(MR)method was used to study the causal relationship between Benign prostatic hyperplasia(BPH),smoking,drinking,number of sexual partners and ED.The principle of MR is that the alleles are randomly assigned during the formation of a fertilized egg.MR uses genetic tools to infer causality,such as Single Nucleotide Polymorphism(SNP),and reduce the impact of potential confounding factors and reverse causality.And MR could help better to understand the causal relationship between exposure and outcome.Method: Demographic statistics,questionnaire results,and laboratory indicators were collected from 2001-2004 in the NHANES database.Clinical data were collected from 2471 men after excluding data containing missing values.Based on the collected cross-sectional clinical data,weighted multi-factor regression analysis was carried out in three different models to find the risk factors related to ED,and then MR method was used to explore the next step of causality.Based on the results of cross-sectional data analysis and previous studies,we selected BPH,smoking,alcohol consumption and number of sexual partners as exposure,and we selected ED as outcome in the MR analysis.Genome-wide association study(GWAS)was used to search ED,BPH,smoking,alcohol consumption and the number of sexual partners.Suitable SNPs were selected as Instrumental Variables(IVs)based on relevant inclusion and exclusion criteria.The selected SNP data was used to conduct a Two-sample Mendelian randomization(TSMR)study by R software(version 4.0.2)to analyze whether there was a causal correlation between BPH,smoking,drinking,number of sexual partners and ED.Results: 1.After fully adjusting for age,education,systolic blood pressure,diastolic blood pressure and diabetes in NHANES data,multivariate logistic regression analysis showed that BPH was an independent risk factor for ED in the 60-70 years group(OR=1.99,95%CI: 1.08,3.65;p=0.03),smoking was also an independent risk factor for ED(OR=1.68,95%CI: 1.04,2.71;p=0.04).2.The results of TSMR analysis showed that:(1)There is a causal relationship between BPH and ED: Inverse variance weighted(IVW): OR=1.130(95%CI:1.014-1.259;p=0.026);MR-Egger showed that the conclusion had no horizontal pleiotropy.Sensitivity analysis by Leave one out(LOO)showed that the results were robust.(2)There was a causal relationship between smoking,the number of sexual partner and ED: Smoking IVW: OR=1.402(95%CI: 1.084-1.813;p=0.010);IVW of the number of sexual partners: OR=1.580(95%CI: 1.188-2.100;p=0.002).Alcohol consumption IVW: OR=1.233(95%CI: 0.924-1.646;p=0.155),indicating that there was no significant causal relationship between alcohol consumption and ED.Sensitivity analysis by LOO showed that the results were robust.Conclusion: Analysis of cross-sectional data from the NHANES database showed that BPH and smoking were associated with ED and were risk factors for ED in older men relative to middle-aged men.TSMR analysis based on GWAS data showed that smoking,BPH,the number of sexual partners had significant causal correlation with ED,which was an exact risk factor for ED.The conclusion provides evidence and genetic support for the causal relationship between BPH,smoking,number of sexual partners and the ED.