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

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...

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Bibliographic Details
Published in:Nature communications Vol. 7; no. 1; pp. 13555 - 11
Main 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 29.11.2016
Nature Publishing Group
Nature Portfolio
Subjects:
631/208/177
631/208/248/144
692/699/2743/137/1418
Biology
Cancer
Cell cycle
Cell division
Clinical Medicine
College campuses
CpG Islands - genetics
Diabetes
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 1 - immunology
Disease
Disease genetics
DNA methylation
DNA Methylation - genetics
Endocrinology
Endocrinology and Diabetes
Endokrinologi och diabetes
Epigenetics
Epigenomics
Fetal Blood - metabolism
Gene expression
Genetic factors
Genomes
Genomics
Health care
Humanities and Social Sciences
Humans
Klinisk medicin
Medical and Health Sciences
Medicin och hälsovetenskap
Medicine
Molecular Sequence Annotation
multidisciplinary
Pathogenesis
Pediatrics
Science
Science (multidisciplinary)
Time Factors
Twins, Monozygotic - genetics
Type 1 diabetes
Canada
Montreal Quebec Canada
Singapore
United Kingdom > UK
Germany
Spain
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. The incidence of type 1 diabetes is increasing, potentially implicating non-genetic factors. Here the authors conduct an epigenome-wide association study in disease-discordant twins and find increased DNA methylation variability at genes associated with immune cell metabolism and the cell cycle.
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These authors contributed equally to this work
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms13555