Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 53 10 2024 09 30 2307 2317 Dujuan Mao Department of Anesthesiology, Huanggang Central Hospital Affiliated to Yangtze University, Huanggang 438000, Hubei, China Shan Li Department of Anesthesiology, Huanggang Central Hospital Affiliated to Yangtze University, Huanggang 438000, Hubei, China Xiufang Li Department of Anesthesiology, Huanggang Central Hospital Affiliated to Yangtze University, Huanggang 438000, Hubei, China Lijuan You Department of Anesthesiology, Huanggang Central Hospital Affiliated to Yangtze University, Huanggang 438000, Hubei, China Jiaqi Yu Department of Anesthesiology, Huanggang Central Hospital Affiliated to Yangtze University, Huanggang 438000, Hubei, China Yaohua Wu Department of Anesthesiology, Huanggang Central Hospital Affiliated to Yangtze University, Huanggang 438000, Hubei, China Quanshui Hao Department of Anesthesiology, Huanggang Central Hospital Affiliated to Yangtze University, Huanggang 438000, Hubei, China Heng Du Department of Gastrointestinal Surgery, Huanggang Central Hospital Affiliated to Yangtze University, Huanggang, 438000, Hubei, China 2024 03 25 2024 08 07 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. https://ijph.tums.ac.ir/index.php/ijph/article/view/34985 https://ijph.tums.ac.ir/index.php/ijph/article/download/34985/8371