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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Veröffentlicht in:	Nature communications Jg. 7; H. 1; S. 13555 - 11
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 29.11.2016 Nature Publishing Group Nature Portfolio
Schlagworte:	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
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms13555