Causal Relationships between Circulating Immune Cell Traits and the Risk of Rheumatoid Arthritis and Osteoarthritis: A Bidirectional Two-Sample Mendelian Randomization Study

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic joint disorders with immunological pathogenesis. However, the causal relationships between circulating immune cells and them remain largely unknown. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) study to determine their causal relationship. Methods: Genome-wide association study summary statistics were extracted from publicly available databases regarding immune cell phenotypes, RA, and OA. MR analysis was conducted using five MR methods, with inverse-variance-weighted (IVW) as the primary analysis method. False discovery rate correction (FDR) was used to reduce the likelihood of type 1 errors. We also conducted MR-Egger intercept tests to evaluate horizontal pleiotropy. Results: After FDR adjustment of the P values for the IVW method, the CD27 expression on memory B cells was negatively related to the risk of RA (P < 0.001), and the human leukocyte antigen (HLA)--DR expression on CD14+ monocytes was negatively related to the risk of OA (P < 0.001). We also found that RA was negatively associated with the expression of HLA-DR on myeloid dendritic cells (P < 0.001), but significant horizontal pleiotropy was observed. Conclusion: Our study demonstrates a causal relationship between specific immune cell traits and RA as well as OA, providing further insight into the role of immune cells in the pathogenesis of these disorders.