Asthma and the risk of gastrointestinal disorders: a Mendelian randomization study

Abstract

Background: The question of whether asthma is causally related to gastrointestinal disorders remained unanswered so far. Thus, this study investigated whether there is such a relation and whether the time of onset of asthma plays a role in the occurrence of the following gastrointestinal disorders: peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) including the distinction between Crohn's disease (CD) and ulcerative colitis (UC).

Methods: Using summary data of genome-wide association studies (GWASs), we ran Mendelian randomization analyses based on up to 456,327 European participants. Outlier assessment, a series of sensitivity analyses and validation of IBD results in a second GWAS were performed to confirm the results.

Results: Presented ORs represent the average change in the outcome per 2.72-fold increase in the prevalence of the exposure. Genetically predicted childhood-onset asthma was positively associated with PUD, GORD, and IBS with similar odds ratios near 1.003 and adjusted P-values from 0.007 (GORD) to 0.047 (PUD). Furthermore, it was inversely related to IBD (OR = 0.992, 95% CI: 0.986, 0.998, adjusted P = 0.023) and suggestively associated with its UC subtype (OR = 0.990, 95% CI: 0.982, 0.998, adjusted P = 0.059). There were no associations between genetically predicted adult-onset asthma and the mentioned gastrointestinal disorders.

Conclusions: This study provides evidence that the presence of asthma onset in childhood increases the risk for GORD, PUD, and IBS but decreases the risk for IBD in adults. The lower risk for IBD may be attributed to a lower risk primarily for UC.

Keywords: Asthma; Crohn’s disease; Gastroesophageal reflux disease; Gastrointestinal disorders; Inflammatory bowel disease; Irritable bowel syndrome; Mendelian randomization; Peptic ulcer disease; Ulcerative colitis.

Fig. 1

Estimates given as odds ratios (ORs) and 95% confidence intervals for the effect of childhood- and adult-onset asthma on peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Estimates were derived by the inverse-variance weighted method with modified second-order weights. Reported P-values were adjusted for multiple testing using the Benjamini-Hochberg procedure. Gray estimates represent the results before and black estimates the results after outlier-removal. PUD, peptic ulcer disease; GORD, gastroesophageal reflux disease; IBS, irritable bowel syndrome; IBD, inflammatory bowel disease

Fig. 2

Estimates given as odds ratios (ORs) and 95% confidence intervals for the effect of childhood- and adult-onset asthma on peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Estimates were derived by the multiplicative random effects inverse-variance weighted method (except the effect of adult-onset asthma on ulcerative colitis that was estimated by the Wald atio approach). Reported P-values were adjusted for multiple testing using the Benjamini-Hochberg procedure. Gray estimates represent the results before and black estimates the results after outlier-removal. IBD, inflammatory bowel disease; CD, Crohn’s disease; UC, ulcerative colitis