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

Christa Meisinger; Dennis Freuer

doi:10.1016/j.semarthrit.2022.151992

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

Semin Arthritis Rheum. 2022 Aug:55:151992. doi: 10.1016/j.semarthrit.2022.151992. Epub 2022 Mar 9.

Authors

Christa Meisinger¹, Dennis Freuer²

Affiliations

¹ Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Augsburg 86156, Germany. Electronic address: christine.meisinger@med.uni-augsburg.de.
² Chair of Epidemiology, University of Augsburg, University Hospital Augsburg, Augsburg 86156, Germany.

PMID: 35303571
DOI: 10.1016/j.semarthrit.2022.151992

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.

MeSH terms

Arthritis, Rheumatoid* / genetics
Colitis, Ulcerative* / complications
Colitis, Ulcerative* / genetics
Crohn Disease* / complications
Crohn Disease* / genetics
Genome-Wide Association Study
Humans
Inflammatory Bowel Diseases* / complications
Inflammatory Bowel Diseases* / genetics
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide