Association analysis of immunophenotypes with ulcerative colitis: A two- sample Mendelian randomization study

Background Immune cells change in Ulcerative colitis (UC). However, the causal relationship between the immunophenotypes and UC is not clear. Methods 731 immunophenotype databases and the UC database with 463,010 participants were utilized. Five Mendelian randomization (MR) analysis methods were used, with inverse variance weighted (IVW) as the main method and single nucleotide polymorphisms (SNPs) as the instrumental variable (IV), to explore the causal relationship. False discovery rate (FDR) correction and sensitivity analysis were used to examine the MR hypothesis. Next, the MR results were cross-verified in FinnGen Consortium R9 with 369,652 participants to confirm the reliability. Finally, reverse MR is performed. Results At the significance level of p < 0.05, 71 immunophenotypes associated with UC were screened. After FDR correction, 7 immunophenotypes were still associated. Cross-analysis of the MR analysis results from the UC database with the MR results from the external IBD (FinnGen) database confirmed that CX3CR1 on CD14 + CD16- monocyte (OR = 1.001, pFDR = 0.075) and CX3CR1 on CD14 + CD16 + monocyte (OR = 1.001, pFDR = 0.002) immunophenotypes were significantly associated with an increased risk of UC. Reverse MR revealed no significant correlations. Conclusion This study verified the causal link between immunophenotypes and UC, which may provide a theoretical basis for developing new targeted drugs.