Effect of the immune cells and plasma metabolites on rheumatoid arthritis: a mediated mendelian randomization study

作者：Qi-Pei Liu, Hong-Cheng Du, Ping-Jin Xie, Sheng-Ting Chai · 发表于：Frontiers in Endocrinology · 年份：2024 · DOI：10.3389/fendo.2024.1438097 · 被引用次数：5 · 研究领域：Genetic Associations and Epidemiology、Rheumatoid Arthritis Research and Therapies、Traditional Chinese Medicine Studies

Background Increasing evidence indicates a close relationship between alterations in human immune cells and plasma metabolites with Rheumatoid Arthritis (RA). However, limited studies have left the causal relationships behind these links unclear. Methods A bidirectional Mendelian Randomization (MR) study was conducted, combined with mediation analysis, using data from genome-wide association study database covering 731 immune cell phenotypes and 1,400 plasma metabolite traits to explore their causal relationships with RA and potential mediating effects. The primary method used for MR analysis was inverse-variance weighted and False Discovery Rate (FDR) correction was applied to verify the robustness of our results. Results HLA DR on CD33- HLA DR+ (myeloid cell group) (OR, 1.422; 95% CI, 1.194–1.694; P < 0.001; P FDR = 0.012) increased the risk of developing RA. CD19 on IgD+ CD38- naive (B cell group) (OR, 0.969; 95% CI, 0.954–0.985; P < 0.001; P FDR = 0.021) reduced the risk of developing RA. RA was a risk factor for HLA DR on CD14- CD16+ monocytes (monocyte group) (OR, 1.242; 95% CI, 1.102–1.401; P < 0.001; P FDR = 0.047). RA was a protective factor for memory B cell %lymphocyte (B cell group) (OR, 0.861; 95% CI, 0.795–0.933; P < 0.001; P FDR = 0.050), CD4+ CD8dim T cell %lymphocyte (TBNK group) (OR, 0.802; 95% CI, 0.711–0.904; P < 0.001; P FDR = 0.043), CD4+ CD8dim T cell %leukocyte (TBNK group) (OR, 0.814; 95% CI, 0.726–0.913; P < ...