Causal relationship between atrial fibrillation and stroke risk: a Mendelian randomization

Objectives: This study aimed to investigate the causal relationship between Atrial Fibrillation (AF) and the risk of Stroke using a Mendelian randomization (MR) approach.Methods: A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) summary statistics data. In this analysis, genetic variants associated with AF were used as instrumental variables to estimate the causal effect. The inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were employed for estimation. Additionally, sensitivity analysis was performed using the leave-one-out method.Results: The analysis included 87 single nucleotide polymorphisms (SNPs) associated with AF. The results from the IVW method indicated a positive association between genetic predisposition to AF and the risk of stroke (OR 1.002, 95 % CI 1.001-1.003, P < 0.001). The weighted median and MR-Egger methods showed consistent results (weighted median: OR 1.001, 95 % CI 1.000-1.002, P = 0.034; MR-Egger: OR 1.001, 95 % CI 1.000-1.003, P = 0.086). Sensitivity analysis demonstrated that no individual SNP significantly influenced the causal inference.Conclusions: This study provides evidence of a causal relationship between AF and an elevated risk of stroke. These findings emphasize the significance of managing AF in order to prevent and treat strokes. Additional research is required to better understand the underlying mechanisms of this causal association.