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Title: Deciphering the role of epigenetics in self-limited epilepsy with centrotemporal spikes.
Austin Authors: Mohandas, Namitha;Loke, Yuk Jing;Mackenzie, Lisa;Bennett, Carmen;Berkovic, Samuel F ;Craig, Jeffrey M;Vadlamudi, Lata
Affiliation: Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Queensland, Australia
Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Royal Brisbane and Women's Hospital, Queensland, Australia
Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, Victoria 3220, Australia
Department of Paediatrics, University of Melbourne, Flemington Road, Parkville, Victoria, Australia
Environmental & Genetic Epidemiology Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria, Australia
Issue Date: Oct-2019 2019-07-04
Publication information: Epilepsy research 2019; 156: 106163
Abstract: The aetiology of self-limited epilepsy with centro-temporal spikes (SECTS) remains controversial and a strong genetic basis has long been presumed. The discordant monozygotic twin (MZ) model controls for shared genetic and environmental factors, enabling focus on the potential role of the non-shared environment. DNA methylation data was acquired from DNA extracted from three discordant MZ twin pairs, from both new born blood spots before epilepsy onset, and blood samples taken after epilepsy onset. An epigenome-wide analysis was performed, using the Illumina Infinium EPIC array. Differentially methylated regions (DMR) were identified using the bumphunter package in R. Comparative analyses were undertaken at the two different time points as well as a combined analysis independent of time. Many of the top DMR-associated genes have previously been described in neurodevelopmental disorders. The LYPD8 gene was associated with a top-ranked DMR both at birth and across the two time points. We have demonstrated the novel utility of the longitudinal, discordant MZ twin model, to facilitate a deeper appreciation of the complex neurobiology of SECTS. The genetic architecture of SECTS is complex and is likely to involve an interplay between genes and environment, in part mediated by epigenetics.
DOI: 10.1016/j.eplepsyres.2019.106163
ORCID: 0000-0003-4580-841X
Journal: Epilepsy research
PubMed URL: 31310899
Type: Journal Article
Subjects: Epigenetics
Monozygotic twins
Self-limited epilepsy with centrotemporal spikes
Appears in Collections:Journal articles

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