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已发表论文
通过系统性药物基因组全范围孟德尔随机化鉴定盆腔器官脱垂的新型疾病修正剂
Authors Liu X , Zhao Z, Wang L
Received 2 March 2025
Accepted for publication 20 September 2025
Published 9 October 2025 Volume 2025:17 Pages 3591—3605
DOI https://doi.org/10.2147/IJWH.S525908
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Vinay Kumar
Xiaochun Liu,1,* Zongyu Zhao,2,* Lin Wang2
1Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China; 2Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaochun Liu, Department of Gynaecology and Obstetrics, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, Shanxi, People’s Republic of China, Email tyxchliu@163.com
Objective: Pelvic organ prolapse (POP) present a significant global health burden, yet effective therapeutic targets remain limited. This study aims to identify potential disease-modifying agents for POP and provide insights to guide the development of targeted therapeutics.
Methods: We integrated data from the druggable genome and expression quantitative trait loci (eQTL) with genome-wide association studies (GWAS) and employed Mendelian randomisation (MR) alongside colocalization analysis to identify potential therapeutic targets. To further elucidate the biological relevance of the identified targets, we performed functional enrichment analyses, including the construction of protein-protein interaction (PPI) networks, Gene Ontology (GO) annotations, and KEGG pathway analysis. Key candidate genes were subsequently evaluated using phenome-wide MR (Phe-MR) to investigate potential adverse effects of these druggable genes on POP treatment.
Results: From two druggable gene sets, two QTLs datasets, four different tissues, and two large-scale POP GWAS datasets, we identified 23 positive targets and 5 druggable genes, including ESR1, DES, and SLC12A2 for whole blood and two tissue-specific genes (ADAMTS5 and PCOLCE2). Enrichment analysis highlighted biological processes involving vagina development, glycosaminoglycan binding, and sulfur compound binding. Phe-MR analysis indicated no significant adverse effects for most genes, except for ESR1 and DES.
Conclusion: This study investigates the biological roles of potential drug targets for POP, identifying promising candidates for future research and drug development in POP treatment.
Keywords: pelvic organ prolapse, druggable genome, Mendelian randomization, enrichment analysis, drug safety evaluation, phenome-wide association study
1Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China; 2Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaochun Liu, Department of Gynaecology and Obstetrics, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, Shanxi, People’s Republic of China, Email tyxchliu@163.com
Objective: Pelvic organ prolapse (POP) present a significant global health burden, yet effective therapeutic targets remain limited. This study aims to identify potential disease-modifying agents for POP and provide insights to guide the development of targeted therapeutics.
Methods: We integrated data from the druggable genome and expression quantitative trait loci (eQTL) with genome-wide association studies (GWAS) and employed Mendelian randomisation (MR) alongside colocalization analysis to identify potential therapeutic targets. To further elucidate the biological relevance of the identified targets, we performed functional enrichment analyses, including the construction of protein-protein interaction (PPI) networks, Gene Ontology (GO) annotations, and KEGG pathway analysis. Key candidate genes were subsequently evaluated using phenome-wide MR (Phe-MR) to investigate potential adverse effects of these druggable genes on POP treatment.
Results: From two druggable gene sets, two QTLs datasets, four different tissues, and two large-scale POP GWAS datasets, we identified 23 positive targets and 5 druggable genes, including ESR1, DES, and SLC12A2 for whole blood and two tissue-specific genes (ADAMTS5 and PCOLCE2). Enrichment analysis highlighted biological processes involving vagina development, glycosaminoglycan binding, and sulfur compound binding. Phe-MR analysis indicated no significant adverse effects for most genes, except for ESR1 and DES.
Conclusion: This study investigates the biological roles of potential drug targets for POP, identifying promising candidates for future research and drug development in POP treatment.
Keywords: pelvic organ prolapse, druggable genome, Mendelian randomization, enrichment analysis, drug safety evaluation, phenome-wide association study