Increased DNA methylation variability in type 1 diabetes across three immune effector cell types

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• dc.contributor.author Paul, Dirk S.ca
• dc.contributor.author Heath, Simonca
• dc.contributor.author Gut, Martaca
• dc.contributor.author Gut, Ivo Glynneca
• dc.contributor.author Leslie, R. Davidca
• dc.date.accessioned 2017-04-26T10:06:55Z
• dc.date.available 2017-04-26T10:06:55Z
• dc.date.issued 2016
• dc.description.abstract The incidence of type 1 diabetes (T1D) has substantially increased over the past decade, suggesting a role for non-genetic factors such as epigenetic mechanisms in disease development. Here we present an epigenome-wide association study across 406,365 CpGs in 52 monozygotic twin pairs discordant for T1D in three immune effector cell types. We observe a substantial enrichment of differentially variable CpG positions (DVPs) in T1D twins when compared with their healthy co-twins and when compared with healthy, unrelated individuals. These T1D-associated DVPs are found to be temporally stable and enriched at gene regulatory elements. Integration with cell type-specific gene regulatory circuits highlight pathways involved in immune cell metabolism and the cell cycle, including mTOR signalling. Evidence from cord blood of newborns who progress to overt T1D suggests that the DVPs likely emerge after birth. Our findings, based on 772 methylomes, implicate epigenetic changes that could contribute to disease pathogenesis in T1D.
• dc.description.sponsorship This work was funded by the EU-FP7 project BLUEPRINT (282510) and the Wellcome Trust (99148).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Paul DS, Teschendorff AE, Leslie RD. Increased DNA methylation variability in type 1 diabetes across three immune effector cell types. Nature Communications. 2016;7:16555. DOI: 10.1038/ncomms13555
• dc.identifier.doi http://dx.doi.org/10.1038/ncomms13555
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/30904
• dc.language.iso eng
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof Nature Communications. 2016;7:16555
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282510
• dc.rights © Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Disease genetics
• dc.subject.keyword Epigenomics
• dc.subject.keyword Type 1 diabetes
• dc.title Increased DNA methylation variability in type 1 diabetes across three immune effector cell typesca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion