Arrhythmias & electrophysiology
Causal association between epilepsy and its DNA methylation profile and atrial fibrillation
Authors' conclusion
FE with HS significantly increases AF risk, highlighting the natural neural-cardiac connection and the need for cardiac monitoring in patients with epilepsy.
Study context
- Population
- Genome-wide association study (GWAS) summary statistics for 10 epilepsy subtypes (International League Against Epilepsy (ILAE)) and atrial fibrillation (AF) (HGRI-EBI Catalog-GWAS); epilepsy-related DNA methylation data (Epigenome-Wide Association Study (EWAS) catalog)epilepsy 29,944 cases, 52,538 controls
- Comparison
- Genetically predicted epilepsy subtypes and epilepsy-related DNA methylation vs risk of AF
- Outcome
- Genetic correlations and bidirectional causality between epilepsy phenotypes and AF
Methodological detailsbidirectional, genome-wide Mendelian randomization (MR), LDSC, epigenetic MR
- Bidirectional
- Genome-wide MR
- LDSC
- Epigenetic MR
Main finding
As reported in the abstract
AF risk
Genetic correlation (LDSC) between 4 epilepsy subtypes and AF, rg
0.116 to 0.241
FE with HS on AF risk (IVW and MR-PRESSO), OR
1.046
P ≤ .004
Further findings
Epigenetic MR: CpG methylation and AF risk
- Lower methylation at cg06222062 (PLA2G5) increases AF risk, OR
- 0.994, P = 3.16E-04
- Lower methylation at cg08461451 (SPPL2B) increases AF risk, OR
- 0.954, P = 1.19E-03
- Higher cg10541930 (C10orf143 promoter) increases AF risk, OR
- 1.043, P = 4.18E-22
- Sensitivity analyses: no pleiotropic bias
- Epilepsy-related DNA methylation data N = ∼800
Original publication
Causal association between epilepsy and its DNA methylation profile and atrial fibrillation. Heart Rhythm. Published 12 September 2024. doi:10.
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