A mendelian randomization study on the association between 731 types of immune cells and 91 types of blood cells with venous thromboembolism.

Abstract

Background: Venous thromboembolism (VTE) is a grave medical condition characterized by the blockage of distant blood vessels due to blood clots or detached vessel wall fragments, leading to ischemia or necrosis of the affected tissues. With the recent introduction of immunothrombosis, the significance of immune cells in the process of thrombus formation has gained prominent attention. Complex cross-talk occurs between immune cells and blood cells during infection or inflammation, with immune cells actively participating in blood clot formation by promoting platelet recruitment and thrombin activation. Nevertheless, comprehensive studies on the genetic association between immune cells phenotypes and VTE remain scarce. This article employed Mendelian randomization (MR) to investigate the association between the incidence of VTE and a range of 731 immune cell types, along with 91 blood cell perturbation phenotypes, utilizing single nucleotide polymorphisms as instrumental variables.

Methods: Through the utilization of publicly available genetic data, a two-sample bi-directional MR analysis was conducted. Sensitivity analyses included Cochran's Q test, MR-Egger intercept test, MR-pleiotropy residual sum and outlier (MR-PRESSO) and leave-one-out analysis. For significant associations, replication analysis was conducted using GWAS data from deep vein thrombosis (DVT) and pulmonary embolism (PE).

Results: We firstly investigated the causal relationship between 731 immune cells and VTE risk. All the GWAS data were obtained from European populations and from men and women. The IVW analysis revealed that CD20 on naive-mature B cell, CD20 on IgD- CD38dim B cell, and CD20 on unswitched memory B cell may increase the risk of VTE (P < 0.05). CD28- CD8dim T cell %T cell, CD64 on monocyte and CD64 on CD14 + CD16- monocyte may be protective factors against DVT (P < 0.05). Then disturbed blood cells types as exposure were analyzed to examine its association with occurrence of VTE. Initial and replication analysis both revealed that environmental KCl-impacted red blood cells and butyric acid-impacted platelet accelerated incidence of VTE (P < 0.05), while colchicine -impacted eosinophil, KCl-impacted reticulocyte and Lipopolysaccharide (LPS) -impacted neutrophil reduced VTE risk (P < 0.05). Sensitivity analyses confirmed the robustness and reliability of these positive findings.

Conclusions: Our study presents evidence of a causal link between six immune cell phenotypes and VTE. Additionally, we have identified two types of blood cells that are associated with both VTE and DVT, and three types of blood cells that are relevant to both VTE and PE.

Clinical trial number: Not applicable.