Rheumatoid arthritis and inflammatory bowel disease: A bidirectional two-sample Mendelian randomization study

Abstract

Objectives: An association between arthritis and inflammatory bowel disease (IBD) was found in observational studies. However, neither the direction nor the cause-effect chain is clear.

Methods: A two-sample Mendelian randomization study was carried out to investigate whether rheumatoid arthritis is causally related to IBD and vice versa. Independent genetic instruments from the largest available genome-wide association study (GWAS) for rheumatoid arthritis (29,880 cases and 73,758 controls) were used to investigate the association with IBD in a sample including European participants (12,882 cases; 21,770 controls). Primary analyses were conducted using the radial inverse-variance weighted (IVW) approach. A number of sensitivity analyses were carried out to assess the robustness of the results.

Results: We found a positive effect of genetically predicted rheumatoid arthritis on IBD as a whole (OR 1.214; 95% CI 1.134; 1.299; P = 3 × 10^-8). In subtype analyses rheumatoid arthritis was suggestively associated with Crohn's disease (CD) (OR 1.108; 95% CI 1.024; 1.199; P = 0.011) and ulcerative colitis (UC) (OR 1.082; 95% CI 1.002; 1.168; P = 0.044). Regarding the other direction, IBD as a whole as well as both subtypes were not related to rheumatoid arthritis.

Conclusions: The present study provides evidence for a link between rheumatoid arthritis and IBD as a whole as well as both subtypes UC and CD. In the other direction no associations could be found. These findings support the clinical need for screening IBD in patients with rheumatoid arthritis.

Keywords: Inflammatory bowel disease; Mendelian randomization; Rheumatoid arthritis.