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心房颤动与中风风险之间的因果关系:一项孟德尔随机化研究。

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

机构信息

Shaanxi University of Chinese Medicine, Xianyang, China.

Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

J Stroke Cerebrovasc Dis. 2023 Dec;32(12):107446. doi: 10.1016/j.jstrokecerebrovasdis.2023.107446. Epub 2023 Oct 31.

Abstract

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.

摘要

目的

本研究旨在采用孟德尔随机化(MR)方法探讨心房颤动(AF)与中风风险之间的因果关系。

方法

采用两样本 MR 分析,使用公开的全基因组关联研究(GWAS)汇总统计数据。在该分析中,将与 AF 相关的遗传变异作为工具变量,以估计因果效应。采用逆方差加权(IVW)法、加权中位数估计和 MR-Egger 回归进行估计。此外,还采用了剔除一个样本的敏感性分析。

结果

分析纳入了 87 个与 AF 相关的单核苷酸多态性(SNP)。IVW 方法的结果表明,AF 的遗传易感性与中风风险之间存在正相关(OR 1.002,95%CI 1.001-1.003,P<0.001)。加权中位数和 MR-Egger 方法的结果一致(加权中位数: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)。敏感性分析表明,没有单个 SNP 显著影响因果推断。

结论

本研究提供了 AF 与中风风险升高之间存在因果关系的证据。这些发现强调了管理 AF 以预防和治疗中风的重要性。需要进一步研究以更好地理解这种因果关联的潜在机制。

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