Evidence map›Paper›PMID 42232515›Full record

ArticleFrontiers in genetics2026

Multi-omics mendelian randomization integrating GWAS and eQTL data revealed potential drug target for irritable bowel syndrome.

Huiwen Ke, Wenchao Chen, Qian Zhang, Zipeng Liu, Pengfei Wei, Li Li, Haitao Yu, Dongmei Huang, Chaoting Lan, Ning Xu and 2 more

Abstract read
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Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Huiwen Ke *Department of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
Wenchao Chen *Department of Pediatrics, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
Qian Zhang *Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Zipeng LiuGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Pengfei WeiGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Li LiLuoyang Women and Children Hospital, Luoyang, Henan, China.
Haitao YuLuoyang Women and Children Hospital, Luoyang, Henan, China.
Dongmei HuangGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Chaoting LanGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Ning XuDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
Lei PiGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Kai SongDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder mainly affecting the young and female with limited therapeutic options, necessitating the identification of novel drug targets. This study aimed to identify and prioritize new, genetically validated drug targets for IBS by leveraging large-scale human genetic data. Methods: We conducted a systematic, druggable genome-wide Mendelian randomization (MR) analysis to evaluate the causal effects of 5,642 potential druggable protein-coding genes on IBS risk. The analysis integrated summary statistics from the largest available IBS genome-wide association study (GWAS), including 53,400 cases and 433,201 controls, with comprehensive blood expression quantitative trait loci (eQTL) data. Significant findings were further validated using colocalization analysis. A phenome-wide association study (PheWAS) was performed to assess the potential for on-target adverse effects. Finally, potential therapeutic compounds were predicted using the Drug Signatures Database (DSigDB) and molecular docking. Results: The MR analysis identified eight genes with potential causal associations with IBS. Following rigorous validation with colocalization analysis, EP300 and P2RY14 emerged as the most promising candidate targets. Genetically predicted higher expression of both EP300 (OR: 1.128, 95% CI: 1.079-1.180) and P2RY14 (OR: 1.118, 95% CI: 1.067-1.172) was suggestively causally associated with an increased risk of IBS. The PheWAS analysis indicated that EP300 and P2RY14 did not show genome-wide significant associations with any other phenotypes. Additionally, molecular docking predicted that existing compounds, such as captopril and menadione, could effectively bind to the EP300 protein. Conclusion: Our study provides genetic evidence establishing EP300 and P2RY14 as promising drug targets for the treatment of IBS, laying a foundation for future drug development and repurposing efforts.

Indexed as

drug repurposingeQTLGWASirritable bowel syndromemendelian randomization

Identifiers

PMID42232515
PMCPMC13225775

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