Genetic Insights into the Connection Between Antibody Responses to Infectious Diseases Agents and Atrial...

Atrial fibrillation (AF) is a prevalent clinical condition associated with significant health risks, including stroke and heart failure. Despite extensive research, the underlying mechanisms of AF remain unclear. Infectious diseases, particularly chronic bacterial and viral infections, have been implicated in AF pathogenesis through inflammatory processes. This study aims to explore the causal relationships between antibody responses to infectious disease agents (ARIDA) and AF using a bidirectional Mendelian randomization (MR) approach. A bidirectional MR study was conducted using genetic data from genome-wide association studies (GWAS). We examined the direct impact of 46 ARIDA phenotypes on AF, as well as the inverse association between AF and these ARIDA phenotypes. SNPs associated with ARIDA phenotypes were used to identify instrumental variables (IVs) based on a criterion of p < 5 × 10^-6. The primary analytic strategy implemented was the inverse variance weighted (IVW) method, and sensitivity studies were conducted to evaluate heterogeneity and pleiotropy. Our MR analysis revealed positive associations between AF risk and antibody levels against Chlamydia trachomatis momp A (OR = 1.016, 95% CI [1.003, 1.029]), anti-human herpes virus 6 IgG seropositivity (OR = 1.013, 95% CI [1.000, 1.026]), and anti-human herpes virus 6 E1A IgG seropositivity (OR = 1.018, 95% CI [1.002, 1.035]). Conversely, anti-Merkel cell polyomavirus IgG seropositivity (OR = 0.984, 95% CI [0.973, 0.996]) and levels of varicella zoster virus glycoproteins E and I (OR = 0.964, 95% CI [0.942, 0.987]) were negatively associated with AF risk. For the reverse analysis, AF was associated with increased levels of antibodies against Epstein - Barr virus VCA p18, human herpes virus 6 IE1B, and human herpes virus 7 U14, and decreased levels of anti-Toxoplasma gondii IgG seropositivity. Sensitivity analyses indicated no significant heterogeneity or pleiotropy. This study suggests potential causal relationships between specific chronic infections and AF, highlighting the complex interactions between immune responses and AF risk. Our findings provide a foundation for future research to explore the underlying mechanisms and develop targeted diagnostic and therapeutic strategies for AF. Further studies are warranted to validate these associations and investigate the potential pathways involved.

The online version contains supplementary material available at 10.1007/s12088-025-01503-x.