Investigating causal associations between inflammatory bowel disease and IgA vasculitis: Univariable and multivariable Mendelian randomization study

Numerous observational studies have suggested a potential shared genetic background between inflammatory bowel disease (IBD) and IgA vasculitis (IgAV). However, the causal relationship between these 2 conditions remains poorly understood. We performed large-scale two-sample and multivariable Mendelian randomization (MR) analyses (MVMR) to examine whether there is a causal relationship between IBD and IgAV. We employed 4 distinct approaches, including MR-Egger, weighted median, random-effects inverse-variance weighted (IVW), and weighted mode, to conduct the MR analysis. The univariable MR analysis demonstrated that IBD and Crohn disease (CD) were associated with an increased risk of IgAV in the International Inflammatory Bowel Disease Genetics Consortium, with an odds ratio (OR) of 1.17 (95% confidence interval [CI]: 1.06–1.28, P IVW = .001) for IBD and an OR of 1.12 (95% CI: 1.01–1.24, P IVW = .016) for CD. Ulcerative colitis was associated with an increased risk of IgAV, which was considered suggestive after Bonferroni correction, with an OR of 1.12 (95% CI: 1.01–1.24, P IVW = .028). Consistent results were observed after adjusting for potential confounders (drug allergy and upper respiratory tract infection) in MVMR. IBD, ulcerative colitis, and CD were associated with an increased risk of IgAV, with an OR of 1.20 (95% CI: 1.08–1.34, P IVW = .001), 1.20 (95% CI: 1.07–1.35, P IVW = .002), and 1.13 (95% CI: 1.03–1.25, P IVW = .0012). Our study identifies a causal relationship between IBD and IgAV, particularly between CD and IgAV, suggesting that IBD is a potential precursor to IgAV rather than the converse. Further studies on the common mechanisms of these 2 diseases are needed.