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

Author:
  • Dirk S. Paul
  • Andrew E. Teschendorff
  • Mary A N Dang
  • Robert Lowe
  • Mohammed I. Hawa
  • Simone Ecker
  • Huriya Beyan
  • Stephanie Cunningham
  • Alexandra R. Fouts
  • Anita Ramelius
  • Frances Burden
  • Samantha Farrow
  • Sophia Rowlston
  • Karola Rehnstrom
  • Mattia Frontini
  • Kate Downes
  • Stephan Busche
  • Warren A. Cheung
  • Bing Ge
  • Marie Michelle Simon
  • David Bujold
  • Tony Kwan
  • Guillaume Bourque
  • Avik Datta
  • Ernesto Lowy
  • Laura Clarke
  • Paul Flicek
  • Emanuele Libertini
  • Simon Heath
  • Marta Gut
  • Ivo G. Gut
  • Willem H. Ouwehand
  • Tomi Pastinen
  • Nicole Soranzo
  • Sabine E. Hofer
  • Beate Karges
  • Thomas Meissner
  • Bernhard O. Boehm
  • Corrado Cilio
  • Helena Elding Larsson
  • Åke Lernmark
  • Andrea K. Steck
  • Vardhman K. Rakyan
  • Stephan Beck
  • R. David Leslie
Publishing year: 2016-11-29
Language: English
Publication/Series: Nature Communications
Volume: 7
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Celiac Unit
  • Cellular Autoimmunity
  • Paediatric Endocrinology
  • ISSN: 2041-1723
E-mail: anita [dot] ramelius [at] med [dot] lu [dot] se

Biomedical analyst

Diabetes and Celiac Unit

+46 40 39 19 06

91:10:018

Jan Waldenströms gata 35, Malmö

36

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00