Abstract
Background
The pathogenesis of atrial fibrillation (AF) is still unclear, and our aim was to understand whether immune cells play a causal role in AF.
Methods
In this study, we conducted an exhaustive Mendelian Randomization (MR) analysis leveraging publicly accessible genetic datasets to investigate the causal relationship between 731 immune cell counts and the risk of AF. Our primary analytical strategies encompassed Mendelian Randomization and sensitivity analyses, employing Inverse Variance Weighted (IVW) and Weighted Median approaches, to ascertain the causal linkage between the immune cell counts under examination and susceptibility to AF. This methodology facilitated a comprehensive evaluation of the potential genetic predispositions influencing AF risk through alterations in immune cell profiles, thereby contributing to a deeper understanding of the etiological mechanisms underlying AF.
Results
Following False Discovery Rate (FDR) adjustment, our findings revealed that AF does not exert a significant impact on immune cell counts. However, a significant association was observed between AF risk and two specific immune cell counts: IgD-CD38dim B cells (Odds Ratio [OR] = 1.049, 95% Confidence Interval [CI] = 1.024–1.075, P = 0.0001, PFDR = 0.039) and CD25 on IgD + CD38dim B cells (OR = 0.974, 95% CI = 0.962–0.986, P = 1.87E-05, PFDR = 0.012).
Conclusions
This study has unveiled a profound interconnection between immune cells and AF, thereby presenting novel therapeutic targets for the diagnosis and treatment of AF.