Causality between Atrial Fibrillation and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study

Abstract

Previous observational studies regarding atrial fibrillation and venous thromboembolism have yielded inconsistent conclusions, and the causal relationship between the two remains unclear. This study aimed to assess the causal effects of atrial fibrillation with venous thromboembolism (consisting of pulmonary embolism and deep vein thrombosis), by the bidirectional two-sample Mendelian randomization analysis. The bidirectional two-sample Mendelian randomization analysis was performed based on publicly available summary-level data obtained in large-scale genome-wide association studies conducted among the European populations. The primary method for estimating causal relationships was inverse variance weighting, supplemented by weighted median, weighted mode, and Mendelian randomization-Egger regression for assessing the result robustness. To guarantee the robustness of our findings, results obtained through the weighted median method were adopted, which indicated the absence of potential causal impact of atrial fibrillation on venous thromboembolism or pulmonary embolism. Besides, atrial fibrillation showed no significant causality with deep vein thrombosis. Similarly, venous thromboembolism did not exhibit any significant causality with atrial fibrillation, pulmonary embolism and atrial fibrillation, or deep vein thrombosis and atrial fibrillation. The present Mendelian randomization analysis suggests that atrial fibrillation and venous thromboembolism have no significant causal association in both directions.