Blood Cells and Venous Thromboembolism Risk: A Two-Sample Mendelian Randomization Study

BACKGROUND: Previous studies have shown that various cell indices are associated with a higher risk of venous thromboembolism (VTE), however, whether these findings reflect a causal relationship remains unclear. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to assess the causal association of various blood cells with VTE risk. STUDY DESIGN AND METHODS: Summary statistics of genetic instruments representing cell indices for erythrocytes, leukocytes, and platelets were extracted from genome-wide association studies of European ancestry, by Two-Sample Mendelian Randomization. Inverse variance weighting (IVW) was used as the primary analytical method for MR. Sensitivity analyses were performed to detect horizontal pleiotropy and heterogeneity. RESULTS: Genetically predicted red blood cell distribution width, mean reticulocyte volume, and mean red blood cell volume were positively associated with VTE, with odds ratio (OR) of 1.002 [CI 1.000–1.003, P = 0.022), 1.003 (CI 1.001–1.004, P = 0.001, respectively)] and 1.001 (CI 1.000–1.002, P = 0.005). Genetically predicted monocyte count was negatively correlated with VTE, with OR = 0.998 (CI 0.996–0.999, P = 0.041). CONCLUSION: Genetically liability to high- red blood cell distribution width, mean reticulocyte volume, mean red blood cell volume, and low monocyte count are associated with the higher risk of VTE. Targeting these factors might be a potential strategy to prevent VTE.