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

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.

Causal association of gastroesophageal reflux disease on irritable bowel syndrome: a two-sample Mendelian randomization study

“…Similarly, in a comparative study in Taiwan including 273 GERD patients, it was discovered that GERD was associated with an increased risk of IBS ( Lei et al, 2019 ). Furthermore, a recent MR study has observed a causal association between GERD and IBS, which supports our findings to a certain extent ( Li et al, 2023 ). However, in their study, patients with IBS had an increased risk of developing GERD, which is inconsistent with our findings.…”

The Time-Varying Impact of COVID-19 on the Acute Kidney Disorders: A Historical Matched Cohort Study and Mendelian Randomization Analysis

“…In conclusion, our study utilized both observational and one-sample MR approaches to systematically investigating the causal relationship between COVID-19 and various kidney diseases. While randomized controlled trials are the benchmark for causal inference, MR offers a valuable alternative method that is both time-efficient and cost-effective [ 30 ]. Furthermore, we applied extensive and complementary sensitivity analyses to address potential confounders due to pleiotropy.…”

“…Initially, a logistic regression model was used to analyze the effect of exposure variables—scaled polygenic risk scores for mild, moderate, and severe COVID-19—against the outcome of COVID-19. This model was adjusted for continuous age, sex (defined as male or female), and the first 10 genetic principal components (continuous variables) [ 30 ]. In the subsequent stage, the scaled predicted exposure values from the first step, which indicate COVID-19 phenotypes, were analyzed for their association with the presence of acute kidney disorder using a Cox proportional hazards regression model.…”

Can physical exercise help people with irritable bowel syndrome? How substantial is the evidence?

“…Although IBS is not a life-threatening syndrome, people with IBS have a reduced quality of life (QoL) [9,10]. The IBS is also closely linked to several psychological comorbidities, such as anxiety and depression, which are the most prominent causes of global disability [11].…”

“…The IBS is also closely linked to several psychological comorbidities, such as anxiety and depression, which are the most prominent causes of global disability [11]. In essence, the disorder presents a variety of irritating symptoms, particularly abdominal pain, bloating, constipation, or diarrhea which interfere with patients' lifestyles and result in higher absenteeism and costs, poor productivity, and reduced educational, social, and occupational achievements [5][6][7][8][9][10][11][12]. Patients with IBS utilize more healthcare resources and services than healthy people [11].…”