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Article Abstract
Background: Erectile dysfunction (ED) is a prevalent condition with current treatments limited by suboptimal efficacy and adverse effects. Mendelian randomization (MR) offers a promising approach to identify potential genetic targets for novel therapies.
Aim: We performed a genome-wide MR study on druggable genes to find ED therapies.
Methods: We collected data on drug-targetable genes and their impact on blood expression quantitative trait loci (eQTLs). Using two-sample MR with genome-wide association studies data, we pinpointed genes linked to ED and conducted enrichment analysis. We also built protein networks and predicted drugs to support treatment development.
Outcomes: This comprehensive strategy provides a robust framework for the advancement of more efficacious and precisely targeted treatments for ED.
Results: The MR analysis identified 124 genes significantly associated with ED. Enrichment analysis revealed these genes are involved in signal transduction, protein phosphorylation, plasma membrane, cytoplasm, ATP binding, and the PI3K-Akt signaling pathway. We identified the top 10 hub genes: PRKCA, IFNG, ITGB1, PPARG, PTK2, LAMA5, BCL2L1, CD3D, CD3E, and CD27. Our study highlighted three potential drugs targeting three of these hub genes: benztropine for CD27, teplizumab for CD3E, and natalizumab for ITGB1.
Clinical Translation: The study identifies high-priority targets for ED therapy, including approved drugs amenable to rapid repurposing trials.
Strengths And Limitations: Multi-omics integration enhanced causal validity; drug predictions leveraged existing therapeutic knowledge. Tissue-specific expression quantitative trait loci confounders and lack of experimental validation for prioritized drugs require caution.
Conclusion: This work advances ED research by mapping druggable genes (PRKCA, IFNG, ITGB1) and pathways via MR, offering precision medicine opportunities and actionable drug repurposing candidates.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358251 | PMC |
| http://dx.doi.org/10.1093/sexmed/qfaf056 | DOI Listing |
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