Yao Yiren, Liu Hongyang, Gu Yang, Xu Xiaojin, Zhang Xiwen
Department of Cardiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Front Cardiovasc Med. 2024 Apr 11;11:1351495. doi: 10.3389/fcvm.2024.1351495. eCollection 2024.
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 ( = 138,086, ncase = 27,205) and AF ( = 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); = 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.
采用孟德尔随机化（MR）方法研究肌萎缩侧索硬化症（ALS）与心房颤动（AF）之间的关联。
使用来自全基因组关联研究（GWAS）的遗传信息进行两样本MR分析。与ALS和AF密切相关的基因变异用作工具变量。ALS（n = 138,086，病例数 = 27,205）和AF（n = 1,030,836，病例数 = 60,620）的GWAS遗传数据可从IEU Open公开获取。具体的MR方案包括逆方差加权（IVW）、简单模式、MR-Egger、加权模式和加权中位数估计器（WME）。随后，使用MR-Egger截距和Cochran Q检验来评估工具变量（IVs）的异质性和乘性效应（IVs）。此外，进行MR-PRESSO分析以排除任何潜在的多效性。
IVW方法表明，ALS对AF有正向影响[比值比（OR）：1.062，95%置信区间（CI）（1.004 - 1.122）；P = 0.035]。实际上，其他MR方法与IVW方法的趋势一致（所有OR > 1），敏感性测试验证了该MR结果的可靠性。
这项MR研究证明了ALS与心房颤动之间存在正向因果关系。有必要进一步研究以阐明连接ALS和AF的机制。
