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. 2023 Jan 31;12(3):1106.
doi: 10.3390/jcm12031106.

The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study

Chunyang Li  1   2 , Yilong Chen  1   2 , Yi Chen  3 , Zhiye Ying  1   2 , Yao Hu  1   2 , Yalan Kuang  1   2 , Huazhen Yang  1   2 , Huan Song  1   2 , Xiaoxi Zeng  1   2
Affiliations

The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study

Chunyang Li et al. J Clin Med. .

Abstract

Background: This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods: In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results: Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 × 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 × 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 × 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 × 10-5). The causality of these associations was observed in female only, but not men.

Conclusions: Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.

Keywords: individual-level Mendelian randomization; irritable bowel syndrome; phenome-wide association study; summary-level Mendelian randomization.

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Conflict of interest statement

The authors disclose no conflict of interest.

Figures

Figure 1
Figure 1
The flow of participants through the study. QC—quality control; GWAS—genome-wide association study; IBS—irritable bowel syndrome; PRS—polygenic risk score; PheWAS—phenome-wide association study; MR—Mendelian randomization.
Figure 2
Figure 2
Forest plot of individual-level MR estimates for association between IBS and the outcomes identified in PheWAS in total and sex-stratified population. IBS—irritable bowel syndrome; PheWAS—phenome-wide association study; MR—Mendelian randomization; OR—odds ratio; CI—confidence interval; GERD—gastro-esophageal reflux disease.
Figure 3
Figure 3
Summary-level MR estimates from each method for the assessment of the causal effects of IBS on five disease outcomes. IBS—irritable bowel syndrome; MR—Mendelian randomization; OR—odds ratio; CI—confidence interval; GERD—gastro-esophageal reflux disease; IVW—inverse-variance.
See this image and copyright information in PMC

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