Abstract
Abstract
Background
Previous observational studies have identified an association between rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, the causal relationship between RA and IBD in the East Asian population remains uncertain.
Methods
The two-sample Mendelian randomization (MR) analysis was conducted to elucidate the potential causal relationship between RA and IBD. Summary-level data from genome-wide association studies (GWAS) in the East Asian population were utilized, including RA (n = 19,190) and IBD (n = 6543), including Crohn's disease (CD, n = 5409) and ulcerative colitis (UC, n = 4853). The inverse variance weighted (IVW) method was employed as the primary analysis, supplemented by weighted median, weighted mode, simple median, MR-Egger, and MR-PRESSO analyses. Sensitivity analyses were conducted to assess the robustness of the results. Genetic data for RA (n = 22,515) were utilized to validate the findings in the East Asian population.
Results
The IVW method showed no significant association between genetically predicted RA and overall IBD in the East Asian population (OR = 1.028; 95% CI: 0.935–1.129; P = 0.567). The subgroup analysis revealed a positive association between RA and CD (OR = 1.268; 95% CI: 1.108–1.451; P < 0.001), while a negative association was observed with UC (OR = 0.839; 95% CI: 0.710–0.993; P = 0.041). These findings were supported by another set of RA data. Additionally, an SNP rs2071475 was identified to play an important role in CD and UC.
Conclusion
This study revealed a potential increased susceptibility to CD and a decreased susceptibility to UC in the East Asian population with RA. Furthermore, a key SNP rs2071475 was discovered along with its opposite effects in CD and UC. These findings provide new evidence for research on the corresponding molecular mechanisms and offer insights for clinical management of RA-associated IBD.
Funder
Key project of Research and development program of Shaanxi Province
Innovation project for medical Integration in XJTU
Free exploration project of the second affiliated hospital of Xi’an Jiaotong University
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology,Immunology