Coronary Artery Disease and Atrial Fibrillation: A Bidirectional Mendelian Randomization Study

Background: Several works of observational clinical research indicate that coronary artery disease (CAD) and atrial fibrillation (AF) aggravate each other. However, it is unknown whether these associations reveal independent causal processes. Objective: The present study aimed to evaluate causal associations between CAD and AF using two-sample Mendelian randomization (TSMR) analysis. Methods: Summary-level Genome-wide association study (GWAS) data for CAD were obtained from the CARDIoGRAMplusC4D consortium, including 60,801 patients and 123,504 controls. General data for AF were acquired from the largest meta-analysis, comprising of 60,620 patients with AF and 970,216 non-cases. After data harmonization, three different methods-inverse-variance weighted (IVW), MR-Egger, and weighted-median-were applied for TSMR analysis. Results: The calculated ORs (95% CIs) for AF using IVW, MR-Egger, and weighted-median analysis were 1.11 (1.05, 1.17; p-value < 0.001), 1.14 (1.00, 1.29; p-value = 0.049), and 1.13 (1.08, 1.19; p-value < 0.001), respectively; for CAD, the results were 1.01 (0.97, 1.04; p-value = 0.76), 0.95 (0.89, 1.02; p-value = 0.15), and 1.00 (0.95, 1.05; p-value = 0.97). Conclusion: This comprehensive TSMR analysis provides evidence that patients with CAD are associated with an increased risk of AF. However, no causal association was found between patients with AF and the risk of CAD. These findings benefit clinical decision-making. Early heart-rhythm monitoring should be performed in patients with CAD. The prevention and treatment of AF complications such as thrombosis may be essential to reduce the incidence of CAD in AF patients.