Abstract
BACKGROUND: Studies have established a strong link between erectile dysfunction (ED) and genetic factors. However, the genetic protective genes associated with ED have yet to be identified. In this study, we used Mendelian randomization (MR) analysis to investigate potential genetic protective genes related to ED. METHODS: We used ED-associated GWAS data and whole blood expression quantitative trait loci (eQTLs) data from the Finnish database, which included 1,154 cases and 94,024 controls, for our analysis, resulting in a total of 95,178 individuals for Mendelian randomization (MR) analysis. To further identify potential causative genes and explore their functional roles and relationship to phenotype, we conducted PPI and single-cell analysis using the GSE206528 dataset. RESULTS: The MR analysis identified 263 genes associated with ED, with TRIP10 showing the highest degree, exhibiting an odds ratio (OR) of 0.58. Located on chromosome 7, TRIP10 plays a protective role in ED. Single-cell sequencing analysis revealed that TRIP10 is most highly expressed in endothelial cells and tissue stem cells, particularly in endothelial cells. Through PPI and single-cell analysis, we further identified potential causative genes, shedding light on their functions and their connection to the phenotype. CONCLUSIONS: Our study found that among the 263 genes associated with ED, TRIP10 was strongly linked to a decreased risk of ED. These findings offer valuable insights for the personalized treatment of ED from a genetic perspective.