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Epigenome-wide association study of seizures in childhood and adolescence
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 associa...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950851/ https://www.ncbi.nlm.nih.gov/pubmed/31915053 http://dx.doi.org/10.1186/s13148-019-0793-z |
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author | Caramaschi, Doretta Hatcher, Charlie Mulder, Rosa H. Felix, Janine F. Cecil, Charlotte A. M. Relton, Caroline L. Walton, Esther |
author_facet | Caramaschi, Doretta Hatcher, Charlie Mulder, Rosa H. Felix, Janine F. Cecil, Charlotte A. M. Relton, Caroline L. Walton, Esther |
author_sort | Caramaschi, Doretta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6950851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69508512020-01-09 Epigenome-wide association study of seizures in childhood and adolescence Caramaschi, Doretta Hatcher, Charlie Mulder, Rosa H. Felix, Janine F. Cecil, Charlotte A. M. Relton, Caroline L. Walton, Esther Clin Epigenetics Research 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. BioMed Central 2020-01-08 /pmc/articles/PMC6950851/ /pubmed/31915053 http://dx.doi.org/10.1186/s13148-019-0793-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Caramaschi, Doretta Hatcher, Charlie Mulder, Rosa H. Felix, Janine F. Cecil, Charlotte A. M. Relton, Caroline L. Walton, Esther Epigenome-wide association study of seizures in childhood and adolescence |
title | Epigenome-wide association study of seizures in childhood and adolescence |
title_full | Epigenome-wide association study of seizures in childhood and adolescence |
title_fullStr | Epigenome-wide association study of seizures in childhood and adolescence |
title_full_unstemmed | Epigenome-wide association study of seizures in childhood and adolescence |
title_short | Epigenome-wide association study of seizures in childhood and adolescence |
title_sort | epigenome-wide association study of seizures in childhood and adolescence |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950851/ https://www.ncbi.nlm.nih.gov/pubmed/31915053 http://dx.doi.org/10.1186/s13148-019-0793-z |
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