Interleukin‐1 receptor type II and inflammatory bowel disease: A Mendelian randomization study

Abstract Background Interleukin‐1 (IL‐1) and its receptor have shown their profound influence on inflammatory bowel disease (IBD). To investigate the relationship between IL‐1 receptor type II (IL‐1RII), a well‐established negative regulator of IL‐1, and IBD along with its subtypes (Crohn's disease [CD] and ulcerative colitis [UC]), we conducted a Mendelian randomization analysis to elucidate the underlying association more clearly. Methods The genome‐wide association studies summary statistics of IL‐1RII were acquired from the INTERVAL study, which involved 3301 European people. The latest meta genome‐wide association studies statistic of IBD/CD/UC served as genetic instruments. Three robust analytical methods including inverse‐variance weighting (IVW), Mendelian randomization (MR)‐Egger regression, and weighted median (WM) were utilized, followed by sensitivity analysis. The MR‐Egger intercept test, Cochran's Q test, and “leave‐one‐out” sensitivity analysis were performed to assess these genetic variants' horizontal pleiotropy, heterogeneities, and stability accordingly. Results The association of genetically increased IL‐1RII [per log‐odds ratio increase] on the increased risk of CD and UC was detected by the IVW method (CD: odds ratio [OR] = 1.077, 95% confidence interval [CI]: 1.019–1.139, p = 0.009; UC: OR = 1.106, 95% CI: 1.008–1.213, p = 0.033). In all analyses, the IVW analysis and MR Egger test showed no significant heterogeneity ( p > 0.05), and the MR Egger intercept test indicated no horizontal pleiotropy ( p > 0.05). Conclusions In this MR analysis, IL‐1RII was identified as a risk factor for CD and UC. This finding has consequently heightened the awareness of the need to thoroughly understand the impact of IL‐1RII on intestinal inflammation.