AI Article Synopsis
- The study investigates the link between different types of epilepsy and atrial fibrillation (AF), aiming to clarify if one condition causes the other.
- Researchers utilized genetic data from large populations to evaluate correlations and potential causal relationships between ten epilepsy subtypes and AF.
- Findings indicate that focal epilepsy with hippocampal sclerosis raises the risk of AF, emphasizing the importance of monitoring heart health in epilepsy patients and identifying specific DNA methylation markers related to this increased risk.
Article 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 Epigenome-Wide Association Study (EWAS) catalog were analyzed to identify causal CpG sites influencing risk of AF through epigenetic MR.
Results: LDSC revealed significant genetic correlations between 4 epilepsy subtypes and AF (correlation coefficient: rg from 0.116 to 0.241). Forward MR suggested a significant causal effect of focal epilepsy with hippocampal sclerosis (focal epilepsy [FE] with hippocampal sclerosis [HS]) on risk of AF (inverse variance weighting [IVW] and Mendelian randomized pleiotropy residual sum and outlier [MR-PRESSO]: odds ratio [OR] = 1.046, P ≤ .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 risk of AF. 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 patients with epilepsy. Specific methylated CpG sites may serve as biomarkers and preventive targets for AF susceptibility.
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| http://dx.doi.org/10.1016/j.hrthm.2024.09.008 | DOI Listing |
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