Blood metabolites as mediators in erectile dysfunction: insights from a multi-center proteomics and genetic study
ObjectiveThis study aims to identify circulating proteins causally associated with erectile dysfunction (ED) using Mendelian randomization (MR) analysis.MethodsWe utilized two of the largest multi-center proteomics databases as exposures and the FinnGen database as the outcome source. A large-scale...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1568780/full |
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| author | Junhao Chen Junxian Zhao Zhi Zhang Xingcheng Zhu Jieming Zuo Zuqing Nie Yuanzhi Fu Haifeng Wang Mengjun Tang Shi Fu |
| author_facet | Junhao Chen Junxian Zhao Zhi Zhang Xingcheng Zhu Jieming Zuo Zuqing Nie Yuanzhi Fu Haifeng Wang Mengjun Tang Shi Fu |
| author_sort | Junhao Chen |
| collection | DOAJ |
| description | ObjectiveThis study aims to identify circulating proteins causally associated with erectile dysfunction (ED) using Mendelian randomization (MR) analysis.MethodsWe utilized two of the largest multi-center proteomics databases as exposures and the FinnGen database as the outcome source. A large-scale two-sample MR analysis, including coloc colocalization analysis and SMR (Summary data-based Mendelian Randomization) analysis, was conducted to evaluate the reliability of proteomic effects on ED outcomes. Additionally, MR mediation analysis involving 1,400 blood metabolites was performed to investigate how these proteins mediate the effect of blood metabolites on ED. Finally, protein-protein interaction analysis, pathway enrichment analysis, druggability assessments, and molecular docking were employed to further elucidate the mechanisms of ED and identify potential therapeutic targets.ResultsEight circulating proteins (AMN, ESM1, KIR2DL2, PIGR, SPINT1, SPP1, TNFRSF6B, TMEM9) were identified as causally associated with ED based on two-sample MR and coloc colocalization criteria. Among these, five proteins (AMN, ESM1, KIR2DL2, PIGR, TNFRSF6B) satisfied SMR validation, while SPINT1, TMEM9, and SPP1 were excluded. Several of these proteins were found to mediate the relationship between metabolites and ED. These proteins are recognized as either druggable targets or existing drug targets, with molecular docking results demonstrating favorable interactions with various drug candidates.ConclusionUsing MR analysis, we identified five proteins associated with ED, clarified protein-mediated mechanisms, and proposed promising therapeutic targets for ED. |
| format | Article |
| id | doaj-art-5ce0a8fb3f5d4e94a24df70f9a135a77 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-5ce0a8fb3f5d4e94a24df70f9a135a772025-08-20T03:34:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15687801568780Blood metabolites as mediators in erectile dysfunction: insights from a multi-center proteomics and genetic studyJunhao Chen0Junxian Zhao1Zhi Zhang2Xingcheng Zhu3Jieming Zuo4Zuqing Nie5Yuanzhi Fu6Haifeng Wang7Mengjun Tang8Shi Fu9Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Urology, 920th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Kunming, Yunnan, ChinaDepartment of Urology, The Central Hospital of Yongzhou, Yongzhou, Hunan Province, ChinaDepartment of Clinical Laboratory, The Second People’s Hospital of Qujing City, Qujing, Yunnan, ChinaDepartment of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of central lab, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaKunming University of Science and Technology, Kunming, ChinaDepartment of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaOrthopedic Department, The 967th Hospital of Joint Logistic Support Force of PLA, Dalian, ChinaDepartment of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaObjectiveThis study aims to identify circulating proteins causally associated with erectile dysfunction (ED) using Mendelian randomization (MR) analysis.MethodsWe utilized two of the largest multi-center proteomics databases as exposures and the FinnGen database as the outcome source. A large-scale two-sample MR analysis, including coloc colocalization analysis and SMR (Summary data-based Mendelian Randomization) analysis, was conducted to evaluate the reliability of proteomic effects on ED outcomes. Additionally, MR mediation analysis involving 1,400 blood metabolites was performed to investigate how these proteins mediate the effect of blood metabolites on ED. Finally, protein-protein interaction analysis, pathway enrichment analysis, druggability assessments, and molecular docking were employed to further elucidate the mechanisms of ED and identify potential therapeutic targets.ResultsEight circulating proteins (AMN, ESM1, KIR2DL2, PIGR, SPINT1, SPP1, TNFRSF6B, TMEM9) were identified as causally associated with ED based on two-sample MR and coloc colocalization criteria. Among these, five proteins (AMN, ESM1, KIR2DL2, PIGR, TNFRSF6B) satisfied SMR validation, while SPINT1, TMEM9, and SPP1 were excluded. Several of these proteins were found to mediate the relationship between metabolites and ED. These proteins are recognized as either druggable targets or existing drug targets, with molecular docking results demonstrating favorable interactions with various drug candidates.ConclusionUsing MR analysis, we identified five proteins associated with ED, clarified protein-mediated mechanisms, and proposed promising therapeutic targets for ED.https://www.frontiersin.org/articles/10.3389/fphar.2025.1568780/fullmendelian randomizationproteomicserectile dysfunctionblood metabolitesprecision therapy |
| spellingShingle | Junhao Chen Junxian Zhao Zhi Zhang Xingcheng Zhu Jieming Zuo Zuqing Nie Yuanzhi Fu Haifeng Wang Mengjun Tang Shi Fu Blood metabolites as mediators in erectile dysfunction: insights from a multi-center proteomics and genetic study Frontiers in Pharmacology mendelian randomization proteomics erectile dysfunction blood metabolites precision therapy |
| title | Blood metabolites as mediators in erectile dysfunction: insights from a multi-center proteomics and genetic study |
| title_full | Blood metabolites as mediators in erectile dysfunction: insights from a multi-center proteomics and genetic study |
| title_fullStr | Blood metabolites as mediators in erectile dysfunction: insights from a multi-center proteomics and genetic study |
| title_full_unstemmed | Blood metabolites as mediators in erectile dysfunction: insights from a multi-center proteomics and genetic study |
| title_short | Blood metabolites as mediators in erectile dysfunction: insights from a multi-center proteomics and genetic study |
| title_sort | blood metabolites as mediators in erectile dysfunction insights from a multi center proteomics and genetic study |
| topic | mendelian randomization proteomics erectile dysfunction blood metabolites precision therapy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1568780/full |
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