Causal role of immune cells in varicose veins: insights from a Mendelian randomization study

Abstract

Abstract Immune factors play a pivotal role in the development of vascular diseases. However, research on the relationship between immune cells and the risk of varicose veins remains limited. In this study, we utilized summary statistics from a genome-wide association study (GWAS) and employed bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between immune cell phenotypes and varicose veins. Sensitivity analyses were conducted to ensure the robustness of the results, including Cochran’s Q test, MR Egger intercept test, leave-one-out analysis, and MR pleiotropy residual sum and outlier (MR-PRESSO) test. Additionally, results were subjected to false discovery rate (FDR) correction. Finally, Bayesian Weighted Mendelian Randomization (BWMR) was utilized to further validate the findings of the MR analysis. Our study identified significant causal associations between 5 immune cell phenotypes and the risk of varicose veins (FDR < 0.05). Specifically, CD86 on myeloid dendritic Cell and CD33 on CD33 + HLA DR + CD14dim show a significant positive causal relationship with the risk of varicose veins, while BAFF-R on IgD- CD24- B cell, BAFF-R on IgD + CD24- B cell, and BAFF-R on IgD + CD38- B cell exhibit a significant negative causal relationship with the risk of varicose veins. Additionally, when FDR was adjusted to 0.2, we found additional 7 immune cell phenotypes that are potentially associated with the risk of varicose veins. In particular, CD33 on CD33 + HLA DR+, CD33 on CD33 + HLA DR + CD14-, CD4 + T cell %T cell and CD39 + CD8 + T cell %CD8 + T cell are positively associated with the risk of varicose veins. In contrast, BAFF-R on B cell, BAFF-R on memory B cell and PDL-1 on CD14- CD16 + monocyte are negatively associated with the risk of varicose veins. The sensitivity analyses yielded results consistent with the main findings. Upon testing with the BWMR method, all results were consistent with those from the MR analysis, except for CD39 + CD8 + T cell %CD8 + T cell. Our study confirms a potential causal relationship between immune cells and varicose veins. This study provides new avenues to explore the mechanisms of varicose veins and lays the foundation for future investigations into targeted prevention strategies.

Keywords

• Varicose veins
• Immune cells
• Mendelian randomization study
• Genetic causality