Mendelian randomization analysis reveals causality of inflammatory bowel disease on risks of Henoch-Schönlein purpura and immune thrombocytopenia

Abstract

Background: Emerging clinical evidence has been discovered associating Inflammatory bowel disease (IBD) with Henoch-Schönlein purpura (HSP) and immune thrombocytopenia (ITP). However, it is unclear whether a cause-effect relationship exists between them. We aimed to examine the casual effect of IBD on the risk of HSP and ITP.

Methods: Based on summary statistics from International IBD Genetics (IIBDG) Consortium and FinnGen study, a two-sample Mendelian randomization study was carried out to determine whether IBD including ulcerative colitis (UC) and Crohn's disease (CD) is causally related to HSP, ITP or secondary thrombocytopenia. To support the results, a variety of sensitivity analyses were performed.

Results: Significant causal relationships between IBD and HSP (odds ratios = 1.20, 95% confidence interval: 1.07-1.36, adjusted P = 0.006) and ITP (odds ratios =1.22, 95% confidence interval: 1.08-1.38, adjusted P = 0.006) were found. Both genetically predicted UC and CD were positively related with ITP, while CD alone may be responsible for the higher risk of HSP. Besides, no significant association was observed between IBD and secondary thrombocytopenia.

Conclusions: The results of this Mendelian randomization study supported the causal association of IBD with HSP and ITP. Taken together, our findings may present implications for management of IBD.

Keywords: Henoch-Schönlein purpura; Immune thrombocytopenia; Inflammatory bowel disease; Mendelian randomization.