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

TL;DR

This study finds a causal link between amyotrophic lateral sclerosis and atrial fibrillation using genetic data.

Contribution

It provides the first evidence of a positive causal association between ALS and AF using Mendelian randomization.

Findings

ALS has a positive causal effect on AF (OR: 1.062, 95% CI 1.004–1.122).

Multiple MR methods confirmed the same trend, supporting the reliability of the result.

Abstract

To look into the connection between amyotrophic lateral sclerosis (ALS) and atrial fibrillation (AF) using Mendelian randomization (MR).

Two-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.

The 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.

This MR study proves a positive causal connection between ALS and atrial fibrillation. Further studies are warranted to elucidate the mechanisms linking ALS and AF.

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