Causal association analysis between 731 immune cells and cystitis: A 2-sample, bidirectional Mendelian randomization study

The causal relationship between certain immune cells and cystitis remains uncertain. This study utilized genome-wide association studies and Mendelian randomization (MR) to investigate the causal relationships between 731 immune cells and cystitis. In this study, we identified genetic instruments for 731 immune cells using genome-wide association studies and obtained cystitis data from the UK Biobank database. We then conducted bidirectional MR analyses to explore the potential causal relationships between these immune cells and cystitis, primarily employing the inverse-variance weighted method. Pleiotropy and heterogeneity were assessed using Cochran Q-test and the MR-Egger intercept test. The results identified 12 immune cells associated with cystitis. Increased levels of CD24 + CD27 + B cell %B cell, Naive-mature B cell Absolute Count, BAFF-R on IgD- CD38dim B cell, CD28 + CD4-CD8-T cell Absolute Count, Naive CD4-CD8-T cell %T cell and CCR2 on monocyte were found to suppress the occurrence of cystitis. Conversely, increased levels of IgD-CD38dim B cell %lymphocyte, IgD-CD38dim B cell %B cell, CD8 on Central Memory CD8 + T cell, CD4 + CD8dim T cell Absolute Count, CD8 on CD8 + T cell and CD25 on IgD-CD27-B cell were associated with promoting cystitis. In reverse MR analyses, using a significance threshold of P <.01, we found that cystitis reduced the counts of certain immune cells, including CD45RA + CD8 + T cell %CD8 + T cell, CD24 on unswitched memory B cell, CCR2 on CD14- CD16 + monocyte. Additionally, cystitis was found to increase the counts of Effector Memory CD8 + T cell %CD8 + T cell, CD28- CD25++ CD8 + T cell %T cell, CD25 on CD39 + CD4 regulatory T cell. Our MR analysis confirms a bidirectional causal relationship between immune cells and cystitis, providing new insights into potential mechanisms and therapeutic strategies for the future.