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Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
Discovering Potential Drug Targets for Irritable Bowel Syndrome Through Genetic Insights: A Mendelian Randomization
Yitong Li1, Yao Jiao1, Muyuan Wang1
1Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
This study identifies P2RY14 and ATRAID as potential therapeutic targets for irritable bowel syndrome (IBS). Targeting these genes may improve IBS drug development success and reduce costs.
Area of Science:
- Genetics and Genomics
- Gastroenterology
- Pharmacology
Background:
- Irritable bowel syndrome (IBS) is a prevalent gastrointestinal motility disorder with significant healthcare and quality-of-life impacts.
- Current therapeutic options for IBS are limited, necessitating the identification of novel treatment targets.
- Causally supported pathogenic proteins offer promising avenues for IBS therapeutic development.
Purpose of the Study:
- To identify potential therapeutic targets for irritable bowel syndrome (IBS) using a Mendelian randomization (MR) approach.
- To validate identified targets through colocalization analysis and an IBS mouse model.
- To facilitate the prioritization and cost-effective development of novel IBS therapeutics.
Main Methods:
- Mendelian randomization (MR) study utilizing summary data from two large independent IBS cohorts.
- Instrumental variables derived from cis-expression quantitative trait loci (cis-eQTL) data of druggable genes.
- Colocalization analysis and an IBS mouse model were used to confirm therapeutic target potential.
Main Results:
- Four potential drug targets (P2RY14, SLC5A6, ATRAID, IL1RL1) were identified through MR analysis.
- Purinergic receptor P2Y14 (P2RY14) and all-trans retinoic acid-induced differentiation factor (ATRAID) showed robust colocalization with IBS.
- IBS mouse models exhibited altered P2RY14 expression and ATRAID levels in colon tissue.
Conclusions:
- P2RY14 and ATRAID are proposed as novel therapeutic targets for irritable bowel syndrome (IBS).
- Targeting P2RY14 and ATRAID may enhance the success rate of clinical trials for IBS drugs.
- This research could streamline IBS drug development and reduce associated economic burdens.
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