A Mendelian randomisation approach to explore genetic factors associated with erectile dysfunction based on pooled genomic data

基于汇总基因组数据,采用孟德尔随机化方法探索与勃起功能障碍相关的遗传因素

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Abstract

BACKGROUND: Genetic factors are thought to play a major role in erectile dysfunction (ED), but the search for specific ED-related genes remains a mysterious area characterised by limited and inconclusive research. METHODS: Whole blood expression quantitative trait loci (eQTLs) and the GWAS data related to the genetics of ED are derived from a Finnish database, Finngen, which contains a dataset of 1154 cases and 94024 controls, culminating in a total of 95178 individuals under scrutiny. Based on these pooled data, a Mendelian randomisation (MR) analysis of ED was performed. Subsequent analyses of PPI and single cell type expression help identify potential pathogenic genes, revealing the function of genes and their association with phenotypes. RESULTS: After SMR analysis, 110 ED-associated genes were screened, of which MDM4 Degree had the highest value with an OR of 1.8453076, was displaced on chromosome 1, and had a risk of promoting ED. Single-cell sequencing analysis results demonstrate the expression of the MDM4 gene in six cell types, further confirming the role of the MDM4 gene in ED. CONCLUSIONS: Our study showed that among the 110 genes associated with ED, MDM4 was highly associated with an increased risk of ED. These findings strongly support personalised treatment strategies decision-making for ED patients.

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