Causal Association Between Peripheral blood immune cells and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

Immune cells play a crucial role in the onset and progression of rheumatoid Arthritis (RA). we leveraged publicly available Genome-Wide Association Studies (GWAS) data to explore the causal relationship between 731 immune cell traits and RA using the Bidirectional MR analysis. The primary method for causal analysis relies on Inverse Variance Weighting (IVW). To ensure robustness, sensitivity analyses include the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Additionally, gene colocalization analysis and drug target MR are employed to enhance the comprehensiveness of the study.In the forward MR analysis, after FDR correction, 731 immune cell traits had no statistically significant effect on RA. Notably, some phenotypes showed lower P values before adjustment, including 12 different immune cell traits. After gene colocalisation analysis only CD4 on HLA DR+ CD4+ T cells and CD45RA- CD28- CD8+ T cell %T cell shared the same genetic variant as RA. Inverse MR analysis showed that RA was associated with 12 immune cell traits. After gene colocalisation analysis RA was associated with CD28- CD8+ T cell %T cell, Effector Memory CD8+ T cell %T cell, CD8+ Natural Killer T Absolute Count, CD8+ Natural Killer T %lymphocyte, and CD8+ Natural Killer T %T cell share the same genetic variant. No evidence of horizontal pleiotropy or heterogeneity between genetic variants was found (P>0.05), and the "leave-one-out" test confirmed the stability and robustness of the associations. MR analyses of drug targets suggested that CCHCR1 may play an important role in the pathogenesis of RA.This study suggests that specific immune cell traits may play a key role in RA development and could serve as new biomarkers for its diagnosis. Notably, identifying CCHCR1 as a drug target unveils new paths for research and treatment, offering promising opportunities in the field.