A causal association between amyotrophic lateral sclerosis and atrial fibrillation: a two-sample Mendelian randomization study

Abstract

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ObjectivesTo look into the connection between amyotrophic lateral sclerosis (ALS) and atrial fibrillation (AF) using Mendelian randomization (MR).MethodsTwo-sample MR was performed using genetic information from genome-wide association studies (GWAS). Genetic variants robustly associated with ALS and AF were used as instrumental variables. GWAS genetic data for ALS (n = 138,086, ncase = 27,205) and AF (n = 1,030,836, ncase = 60,620), publicly available from IEU Open. The specific MR protocols were Inverse variance-weighted (IVW), Simple mode, MR Egger, Weighted mode, and Weight median estimator (WME). Subsequently, the MR-Egger intercept and Cochran Q examine were used to evaluate instrumental variables (IVs)' heterogeneity and multiplicative effects (IVs). In addition, MR-PRESSO analysis was conducted to exclude any potential pleiotropy.ResultsThe IVW method demonstrated that ALS positively affected AF [OR: 1.062, 95% CI (1.004–1.122); P = 0.035]. Indeed, other MR methods were in accordance with the tendency of the IVW method (all OR > 1), and sensitivity testing verified the reliability of this MR result.ConclusionsThis MR study proves a positive causal connection between ALS and atrial fibrillation. Further studies are warranted to elucidate the mechanisms linking ALS and AF.

Keywords

• amyotrophic lateral sclerosis
• atrial fibrillation
• arrhythmia
• causal relationship
• Mendelian randomization