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Title: Increased DNA methylation variability in type 1 diabetes across three immune effector cell types
Authors: Paul, Dirk S.
Teschendorff, Andrew E.
Dang, Mary A.N.
Lowe, Robert
Hawa, Mohammed I.
Ecker, Simone
Beyan, Huriya
Cunningham, Stephanie
Fouts, Alexandra R.
Ramelius, Anita
Burden, Frances
Farrow, Samantha
Rowlston, Sophia
Rehnstrom, Karola
Frontini, Mattia
Downes, Kate
Busche, Stephan
Cheung, Warren A.
Ge, Bing
Simon, Marie-Michelle
Bujold, David
Kwan, Tony
Bourque, Guillaume
Datta, Avik
Lowy, Ernesto
Clarke, Laura
Flicek, Paul
Libertini, Emanuele
Heath, Simon
Gut, Marta
Gut, Ivo G
Ouwehand, Willem H.
Pastinen, Tomi
Soranzo, Nicole
Hofer, Sabine E.
Karges, Beate
Meissner, Thomas
Boehm, Bernhard O.
Cilio, Corrado
Elding Larsson, Helena
Lernmark, Åke
Steck, Andrea K.
Rakyan, Vardhman K.
Beck, Stephan
Leslie, R. David
Keywords: Epigenomics
Disease Genetics
Issue Date: 2016
Source: Paul, D. S., Teschendorff, A. E., Dang, M. A., Lowe, R., Hawa, M. I., Ecker, S., . . . Leslie, R. D. (2016). Increased DNA methylation variability in type 1 diabetes across three immune effector cell types. Nature Communications, 7, 13555-. doi:10.1038/ncomms13555
Series/Report no.: Nature Communications
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.
DOI: 10.1038/ncomms13555
Rights: © 2016 The Author(s) (Published by 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
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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