Peng Guo, Hongjian Zhang, Rong Cao, Huan Guo, Xu Zhou, Heng Pan, Junwei Lin, Qiusong Liu, Zheng Wan
{"title":"使用全基因组孟德尔随机化确定欧洲人群勃起功能障碍的治疗靶点。","authors":"Peng Guo, Hongjian Zhang, Rong Cao, Huan Guo, Xu Zhou, Heng Pan, Junwei Lin, Qiusong Liu, Zheng Wan","doi":"10.1093/sexmed/qfaf056","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>We performed a genome-wide MR study on druggable genes to find ED therapies.</p><p><strong>Methods: </strong>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.</p><p><strong>Outcomes: </strong>This comprehensive strategy provides a robust framework for the advancement of more efficacious and precisely targeted treatments for ED.</p><p><strong>Results: </strong>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.</p><p><strong>Clinical translation: </strong>The study identifies high-priority targets for ED therapy, including approved drugs amenable to rapid repurposing trials.</p><p><strong>Strengths and limitations: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":21782,"journal":{"name":"Sexual Medicine","volume":"13 4","pages":"qfaf056"},"PeriodicalIF":2.0000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358251/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identifying therapeutic targets for erectile dysfunction in the European population using genome-wide Mendelian randomization.\",\"authors\":\"Peng Guo, Hongjian Zhang, Rong Cao, Huan Guo, Xu Zhou, Heng Pan, Junwei Lin, Qiusong Liu, Zheng Wan\",\"doi\":\"10.1093/sexmed/qfaf056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>We performed a genome-wide MR study on druggable genes to find ED therapies.</p><p><strong>Methods: </strong>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.</p><p><strong>Outcomes: </strong>This comprehensive strategy provides a robust framework for the advancement of more efficacious and precisely targeted treatments for ED.</p><p><strong>Results: </strong>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.</p><p><strong>Clinical translation: </strong>The study identifies high-priority targets for ED therapy, including approved drugs amenable to rapid repurposing trials.</p><p><strong>Strengths and limitations: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":21782,\"journal\":{\"name\":\"Sexual Medicine\",\"volume\":\"13 4\",\"pages\":\"qfaf056\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-08-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358251/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Sexual Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/sexmed/qfaf056\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sexual Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/sexmed/qfaf056","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Identifying therapeutic targets for erectile dysfunction in the European population using genome-wide Mendelian randomization.
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.
期刊介绍：
Sexual Medicine is an official publication of the International Society for Sexual Medicine, and serves the field as the peer-reviewed, open access journal for rapid dissemination of multidisciplinary clinical and basic research in all areas of global sexual medicine, and particularly acts as a venue for topics of regional or sub-specialty interest. The journal is focused on issues in clinical medicine and epidemiology but also publishes basic science papers with particular relevance to specific populations. Sexual Medicine offers clinicians and researchers a rapid route to publication and the opportunity to publish in a broadly distributed and highly visible global forum. The journal publishes high quality articles from all over the world and actively seeks submissions from countries with expanding sexual medicine communities. Sexual Medicine relies on the same expert panel of editors and reviewers as The Journal of Sexual Medicine and Sexual Medicine Reviews.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
