Inflammatory bowel disease and allergic diseases: A Mendelian randomization study

Abstract

AbstractBackgroundInflammatory bowel disease (IBD) and allergic diseases possess similar genetic backgrounds and pathogenesis. Observational studies have shown a correlation, but the exact direction of cause and effect remains unclear. The aim of this Mendelian randomization (MR) study is to assess bidirectional causality between inflammatory bowel disease and allergic diseases.MethodWe comprehensively analyzed the causal relationship between inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) and allergic disease (asthma, Hay fever, and eczema) as a whole, allergic conjunctivitis (AC), atopic dermatitis (AD), allergic asthma (AAS), and allergic rhinitis (AR) by performing a bidirectional Mendelian randomization study using summary‐level data from genome‐wide association studies. The analysis results mainly came from the random‐effects model of inverse variance weighted (IVW‐RE). In addition, multivariate Mendelian randomization (MVMR) analysis was conducted to adjust the effect of body mass index (BMI) on the instrumental variables.ResultsThe IVW‐RE method revealed that IBD genetically increased the risk of allergic disease as a whole (OR = 1.03, 95% CI = 1.01–1.04, fdr.p = .015), AC (OR = 1.04, 95% CI = 1.01–1.06, fdr.p = .011), and AD (OR = 1.06, 95% CI = 1.02–1.09, fdr.p = .004). Subgroup analysis further confirmed that CD increased the risk of allergic disease as a whole (OR = 1.02, 95% CI = 1.00–1.03, fdr.p = .031), AC (OR = 1.03, 95% CI = 1.01–1.05, fdr.p = .012), AD (OR = 1.06, 95% CI = 1.02–1.09, fdr.p = 2E−05), AAS (OR = 1.05, 95% CI = 1.02–1.08, fdr.p = .002) and AR (OR = 1.03, 95% CI = 1.00–1.07, fdr.p = .025), UC increased the risk of AAS (OR = 1.02, 95% CI = 0.98–1.07, fdr.p = .038). MVMR results showed that after taking BMI as secondary exposure, the causal effects of IBD on AC, IBD on AD, CD on allergic disease as a whole, CD on AC, CD on AD, CD on AAS, and CD on AR were still statistically significant. No significant association was observed in the reverse MR analysis.ConclusionThis Mendelian randomized study demonstrated that IBD is a risk factor for allergic diseases, which is largely attributed to its subtype CD increasing the risk of AC, AD, ASS, and AR. Further investigations are needed to explore the causal relationship between allergic diseases and IBD.