The gut-lung axis: Mendelian randomization identifies a causal association between inflammatory bowel disease and interstitial lung disease

Abstract

Background: Previous studies have suggested the association between interstitial lung disease (ILD) and inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC).

Objectives: To examine the potential bidirectional causal relationship between IBD and ILD using the Mendelian randomization (MR) method.

Methods: We obtained the data from the genome-wide association studies (GWASs) in European individuals for IBD (25,042 cases and 34,915 controls) and ILD (21,806 cases and 196,986 controls) from the IEU GWAS database. We screened for instrumental variables based on the three assumptions of MR. The two-sample bidirectional MR analysis was performed using the inverse-variance weighted method and multiple sensitivity analyses.

Results: Genetic liability to IBD was significantly associated with an increased ILD risk (odds ratio (OR) = 1.20, 95% confidence interval (CI) = 1.17-1.24, p = 3.67E-33). When considering the IBD subtypes, ILD risk was associated with genetic liability to both CD (OR = 1.14, 95% CI = 1.10-1.17, p = 1.91E-17) and UC (OR = 1.16, 95% CI = 1.12-1.21, p = 3.51E-13). There was weak evidence for the effect of genetic liability to ILD on IBD (OR = 1.32, 95% CI = 0.99-1.76, p = 0.062), CD (OR = 1.25, 95% CI = 1.00-1.55, p = 0.046), and UC (OR = 1.47, 95%CI = 1.01-2.14, p = 0.046).

Conclusion: The results indicate a strong causal effect of IBD (including CD and UC) on ILD.

Keywords: Causality; Gut-lung axis; Inflammatory bowel disease; Interstitial lung disease; Mendelian randomization.