Rheumatoid Arthritis Likely Plays Causal Role in Inflammatory Bowel Disease

Shot of a young man suffering from stomach pain while lying sitting a sofa at home
Researchers assessed whether rheumatoid arthritis is causally related to inflammatory bowel disease and vice versa.

Rheumatoid arthritis (RA) risk is positively associated with an increased risk for inflammatory bowel disease (IBD), suggesting a causal relationship between RA and IBD, according to findings published in Seminars in Arthritis and Rheumatism.

Researchers sought to better understand bidirectional associations between RA and IBD as a whole, including its subtypes Crohn disease and ulcerative colitis.

The researchers used a Mendelian randomization approach, which assesses genetic variants for causal effects of modifiable exposures on disease. The analysis included summary statistics for RA and IBD from a large European genome-wide association study. Radial inverse-variance weighted Mendelian randomization analyses were used to detect heterogenous genetic variants and calculate causal estimates. Sensitivity analyses were performed to account for different patterns of pleiotropy.

The genome-wide association study included 29,880 cases and 73,758 controls for RA; there were 12,882 cases and 21,770 controls for IBD. There was a positive association between RA and IBD (odds ratio (OR)=1.214; 95% CI, 1.134-1.299; P =3×10-8) and a suggestively positive association with both Crohn disease (OR=1.108; 95% CI, 1.024-1.199; P =.011) and ulcerative colitis (OR=1.082; 95% CI, 1.002-1.168; P =.044).

In the other direction, there were no associations between RA and IBD, Crohn disease, or ulcerative colitis.

Limitations of the study include the potential for pleiotropy and a narrow study population.

The researchers conclude, “In patients with RA it is important that physicians and practitioners pay attention to the development of IBD. The results of the present study thus may contribute to more timely preventive care and better interdisciplinary, holistic patient management. The pathophysiologic pathways associated with the development of IBD in RA patients deserves further investigation.”


Meisinger C, Freuer D. Rheumatoid arthritis and inflammatory bowel disease: A bidirectional two-sample Mendelian randomization study. Semin Arthritis Rheum. Published online March 9, 2022. doi:10.1016/j.semarthrit.2022.151992