Associations of inflammatory cytokines with inflammatory bowel disease: a Mendelian randomization study

Abstract

Objectives: Previous studies have confirmed a link between specific inflammatory cytokines and inflammatory bowel disease (IBD), but the causal relationship between them is not completely clear. This Mendelian Randomization (MR) study aims to evaluate the causal relationship between 18 inflammatory cytokines and inflammatory bowel disease.

Method: Two-sample Mendelian randomization utilized genetic variances associated with IBD from two extensive publicly available genome-wide association studies (GWAS) (Crohn's Disease (CD): 12,194 cases and 28,072 controls; Ulcerative Colitis (UC): 12,336 cases and 33,609 controls). The data of inflammatory cytokines was acquired from a GWAS including 8,293 healthy participants. We used inverse variance weighted method, MR-Egger, weighted median, simple model and weighted model to evaluate the causal relationship between inflammatory cytokines and IBD. Sensitivity analysis includes heterogeneity and pleiotropy analysis to evaluate the robustness of the results.

Results: The findings indicated suggestive positive associations between Interleukin-13 (IL-13) and macrophage migration inhibitory factor (MIF) with CD (odds ratio, OR: 1.101, 95%CI: 1.021-1.188, p = 0.013; OR: 1.134, 95%CI: 1.024-1.255, p = 0.015). IL-13 also displayed a significant positive correlation with UC (OR: 1.099, 95%CI: 1.018-1.186, p = 0.016). Stem cell factor (SCF) was suggested to be associated with the development of both CD and UC (OR: 1.032, 95%CI: 0.973-1.058, p = 0.012; OR: 1.038, 95%CI: 1.005-1.072, p = 0.024).

Conclusion: This study proposes that IL-13 may be a factor correlated with the etiology of IBD (CD and UC), while MIF just be specifically associated with CD. Additionally, SCF appears more likely to be involved in the downstream development of IBD (CD and UC).

Keywords: GWAS; Mendelian randomization; biomarkers; inflammatory bowel disease; inflammatory cytokines.