Causal association between epilepsy and its DNA methylation profile and atrial fibrillation.

IF 5.6 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Heart rhythm Pub Date : 2024-09-09 DOI:10.1016/j.hrthm.2024.09.008

Zequn Zheng, Haohao Chen, Yanbin Chen, Xuerui Tan

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引用次数: 0

Abstract

Background: The "epileptic heart" concept is emerging, but the causal relationship between epilepsy and atrial fibrillation (AF) remains unclarified.

Objective: This study explores the genetic correlations and bidirectional causality between various epilepsy phenotypes and AF.

Methods: Genome-wide association study (GWAS) statistics for 10 epilepsy subtypes (29,944 cases, 52,538 controls) and AF (60,620 cases, 970,216 controls) were sourced from the International League Against Epilepsy (ILAE) and HGRI-EBI Catalog-GWAS, respectively. Linkage disequilibrium score regression (LDSC) and genome-wide Mendelian Randomization (MR) evaluated genetic correlations and bidirectional causal relationships. Epilepsy-related DNA methylation data (N= ∼800) from EWAS catalog were analyzed to identify causal CpG sites influencing AF risk through epigenetic MR.

Results: LDSC revealed significant genetic correlations between four epilepsy subtypes and AF (rg from 0.116 to 0.241). Forward MR suggested a significant causal effect of focal epilepsy with hippocampal sclerosis (FE with HS) on AF risk (IVW and MR-PRESSO: OR = 1.046, P ≤ 0.004), with results robust against heterogeneity, horizontal pleiotropy, and outliers. Epigenetic MR indicated that lower methylation at cg06222062 (OR = 0.994, P = 3.16E-04) mapped to PLA2G5 and cg08461451 mapped to SPPL2B gene (OR = 0.954, P = 1.19E-03), and higher cg10541930 in the C10orf143 promoter (OR = 1.043, P = 4.18E-22) increases AF risk. Sensitivity analyses affirmed no pleiotropic bias.

Conclusion: FE with HS significantly increases AF risk, highlighting the natural neural-cardiac connection and the need for cardiac monitoring in epilepsy patients. Specific methylated CpG sites may serve as biomarkers and preventive targets for AF susceptibility.

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癫痫及其 DNA 甲基化特征与心房颤动之间的因果关系。

背景：癫痫性心脏 "的概念正在兴起，但癫痫与心房颤动（房颤）之间的因果关系仍未明确：本研究探讨了各种癫痫表型与心房颤动之间的遗传相关性和双向因果关系：全基因组关联研究（GWAS）的 10 个癫痫亚型（29,944 个病例，52,538 个对照）和房颤（60,620 个病例，970,216 个对照）的统计数据分别来自国际抗癫痫联盟（ILAE）和 HGRI-EBI Catalog-GWAS。连锁不平衡评分回归（LDSC）和全基因组孟德尔随机化（MR）评估了遗传相关性和双向因果关系。对EWAS目录中与癫痫相关的DNA甲基化数据（N= ∼ 800）进行了分析，以通过表观遗传MR确定影响房颤风险的CpG位点：LDSC显示四种癫痫亚型与房颤之间存在明显的遗传相关性（rg从0.116到0.241）。前向磁共振表明，局灶性癫痫伴海马硬化（FE伴HS）对房颤风险有明显的因果效应（IVW和MR-PRESSO：OR = 1.046，P≤0.004），结果对异质性、水平多义性和异常值都是稳健的。表观遗传 MR 显示，映射到 PLA2G5 的 cg06222062（OR = 0.994，P = 3.16E-04）和映射到 SPPL2B 基因的 cg08461451（OR = 0.954，P = 1.19E-03）的甲基化程度较低，而 C10orf143 启动子中的 cg10541930（OR = 1.043，P = 4.18E-22）较高，会增加房颤风险。敏感性分析证实不存在多效应偏倚：结论：FE伴HS会明显增加心房颤动的风险，这凸显了神经与心脏之间的天然联系以及对癫痫患者进行心脏监测的必要性。特定的甲基化 CpG 位点可作为房颤易感性的生物标志物和预防目标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Heart rhythm 医学-心血管系统

CiteScore

10.50

自引率

5.50%

发文量

1465

审稿时长

24 days

期刊介绍： HeartRhythm, the official Journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society, is a unique journal for fundamental discovery and clinical applicability. HeartRhythm integrates the entire cardiac electrophysiology (EP) community from basic and clinical academic researchers, private practitioners, engineers, allied professionals, industry, and trainees, all of whom are vital and interdependent members of our EP community. The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards.