Association of immune responses to infectious agents with the risk of atrial fibrillation: A two-sample Mendelian randomization study.

Background: Atrial fibrillation (AF) represents the most prevalent form of sustained arrhythmia, with emerging evidence indicating that infectious and inflammatory factors may play a contributory role in its incidence. Methods: Genetic instruments associated with antibody responses to 13 pathogens were obtained from the GWAS Catalog, while summary statistics for atrial fibrillation (AF) were sourced from the Finnish Biobank. A two-sample Mendelian randomization (MR) analysis was conducted, employing inverse variance weighting (IVW) as the primary analytical approach, supplemented by the weighted median estimator (WME) and MR-Egger regression for robustness checks. Results: The inverse-variance weighted (IVW) analysis demonstrated that elevated levels of Epstein-Barr virus (EBV) EBNA-1 antibodies were associated with a decreased risk of atrial fibrillation (AF), with an odds ratio (OR) of 0.961 (95 % confidence interval [CI]: 0.933-0.989, P = 0.006). The weighted median estimator (WME) corroborated these findings, although the MR-Egger regression did not yield significant results. Notable heterogeneity was detected, warranting cautious interpretation of the results. Conclusion: Our findings indicate a possible protective relationship between Epstein-Barr Virus (EBV) EBNA-1 antibody levels and atrial fibrillation (AF). Despite the limitations in establishing causality due to heterogeneity and pleiotropy, this study underscores the significance of infection- and inflammation-related pathways in AF and lays the groundwork for future mechanistic and clinical investigations.