Epigenome-wide association study of seizures in childhood and adolescence

Esther Walton, Doretta Caramaschi, Caroline Relton, Charlie Hatcher, Janine F Felix, Rosa Mulder, Charlotte A.M. Cecil

Research output: Contribution to journalArticle

Abstract

The occurrence of seizures in childhood is often associated with neurodevelopmental impairments and school underachievement. Common genetic variants associated with epilepsy have been identified and epigenetic mechanisms have also been suggested to play a role. In this study, we analyzed the association of genome-wide blood DNA methylation with the occurrence of seizures in ~ 800 children from the Avon Longitudinal Study of Parents and Children, UK, at birth (cord blood), during childhood, and adolescence (peripheral blood). We also analyzed the association between the lifetime occurrence of any seizures before age 13 with blood DNA methylation levels. We sought replication of the findings in the Generation R Study and explored causality using Mendelian randomization, i.e., using genetic variants as proxies. The results showed five CpG sites which were associated cross-sectionally with seizures either in childhood or adolescence (1-5% absolute methylation difference at p FDR < 0.05), although the evidence of replication in an independent study was weak. One of these sites was located in the BDNF gene, which is highly expressed in the brain, and showed high correspondence with brain methylation levels. The Mendelian randomization analyses suggested that seizures might be causal for changes in methylation rather than vice-versa. In conclusion, we show a suggestive link between seizures and blood DNA methylation while at the same time exploring the limitations of conducting such study.

Original languageEnglish
Article number8
JournalCLINICAL EPIGENETICS
Volume12
Issue number1
Early online date8 Jan 2020
DOIs
Publication statusPublished - 8 Jan 2020

Keywords

  • ALSPAC
  • DNA methylation
  • Epigenetics
  • Epilepsy
  • Generation R Study
  • Illumina 450 K
  • Mendelian randomization
  • Seizures

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Cite this

Walton, E., Caramaschi, D., Relton, C., Hatcher, C., Felix, J. F., Mulder, R., & Cecil, C. A. M. (2020). Epigenome-wide association study of seizures in childhood and adolescence. CLINICAL EPIGENETICS, 12(1), [8]. https://doi.org/10.1186/s13148-019-0793-z