Two-sample Mendelian Randomization Study of Metformin and Erectile Dysfunction
OBJECTIVE The potential causal relationship between metformin and erectile dysfunction was ex-plored using the two-sample Mendelian randomization method,and the potential mechanism was explored from the perspective of genetics.METHODS From genome-wide association studies(GWAS)public selected in the data-base associated with metformin,erectile dysfunction of single nucleotide polymorphisms(SNP).In the first step anal-ysis,123 independent SNPs(P<1e-05)related to metformin were selected as effective instrumental variables,taking metformin as exposure and erectile dysfunction as results.In addition,MR Analysis was performed in the second step analysis to eliminate interference from SNPs closely associated with erectile dysfunction.Inverse variance weighted(IVW)method was used to analyze the sensitivity of MR Results through heterogeneity test,pleiotropy test,scatter plot,forest plot and funnel plot.oddsratio(OR)and 95%confidenceinterval(CI)were used as effect indicators to investigate the causal relationship between metformin and erectile dysfunction.RESULTS The IVW methodology indicated that the use of metformin is linked to an increased risk of developing erectile dysfunction(OR=19.52,95%CI=1.13-355.2).The instrumental variables demonstrated robustness with an F-value greater than 10 and showed no evidence of being weak instruments.Both the Cochran's Q test and MR-PRESSO test indicated no signifi-cant heterogeneity or horizontal pleiotropy among the instrumental variables.CONCLUSION There is a significant positive association between the use of metformin and the risk of erectile dysfunction.This finding challenges prior as-sumptions about metformin's role in ED and underscores the need for further research on its implications.