Causal association of peripheral immune cell counts and atrial fibrillation: A Mendelian randomization study

Atrial fibrillation (AF) is the most common and persistent form of arrhythmia. Recently, increasing evidence has shown a link between immune responses and atrial fibrillation. However, whether the immune response is a cause or consequence of AF remains unknown. We aimed to determine whether genetically predicted peripheral immunity might have a causal effect on AF.

First, we performed Mendelian randomization (MR) analyses using genetic variants strongly associated with neutrophil, eosinophil, basophil, lymphocyte, and monocyte cell counts as instrumental variables (IVs). Lymphocyte counts were then subjected to further subgroup analysis. The effect of immune cell counts on AF risk was measured using summary statistics from genome-wide association studies (GWAS).

Two-sample MR analysis revealed that a higher neutrophil count, basophil count and lymphocyte count had a causal effect on AF [Odds ratio (OR), 1.06, 95% confidence interval (CI), 1.01-1.10, P = 0.0070; OR, 1.10; 95% CI, 1.04-1.17; P = 0.0015; OR, 0.96; 95% CI, 0.93-0.99; P = 0.0359]. In addition, in our further analysis, genetically predicted increases in CD4 + T-cell counts were also associated with an increased risk of AF (OR, 1.04; 95% CI, 1.0-.09; P = 0.0493).

Our MR analysis provided evidence of a genetically predicted causal relationship between higher peripheral immune cell counts and AF. Subgroup analysis revealed the key role of peripheral lymphocytes in AF, especially the causal relationship between CD4 + T cell count and AF. These findings are beneficial for future exploration of the mechanism of AF.