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

Author

Listed:
  • Dirk S. Paul

    (Medical Genomics, UCL Cancer Institute, University College London
    Cardiovascular Epidemiology Unit, University of Cambridge, Strangeways Research Laboratory)

  • Andrew E. Teschendorff

    (CAS Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences
    Statistical Cancer Genomics, UCL Cancer Institute, University College London)

  • Mary A.N. Dang

    (The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Robert Lowe

    (The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Mohammed I. Hawa

    (The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Simone Ecker

    (Medical Genomics, UCL Cancer Institute, University College London)

  • Huriya Beyan

    (The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Stephanie Cunningham

    (The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Alexandra R. Fouts

    (Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine)

  • Anita Ramelius

    (Lund University, Skåne University Hospital)

  • Frances Burden

    (University of Cambridge, Cambridge Biomedical Campus
    National Health Service Blood and Transplant, Cambridge Biomedical Campus)

  • Samantha Farrow

    (University of Cambridge, Cambridge Biomedical Campus
    National Health Service Blood and Transplant, Cambridge Biomedical Campus)

  • Sophia Rowlston

    (University of Cambridge, Cambridge Biomedical Campus
    National Health Service Blood and Transplant, Cambridge Biomedical Campus)

  • Karola Rehnstrom

    (University of Cambridge, Cambridge Biomedical Campus
    National Health Service Blood and Transplant, Cambridge Biomedical Campus)

  • Mattia Frontini

    (University of Cambridge, Cambridge Biomedical Campus
    National Health Service Blood and Transplant, Cambridge Biomedical Campus
    British Heart Foundation Centre of Excellence, Cambridge Biomedical Campus)

  • Kate Downes

    (University of Cambridge, Cambridge Biomedical Campus
    National Health Service Blood and Transplant, Cambridge Biomedical Campus)

  • Stephan Busche

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • Warren A. Cheung

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • Bing Ge

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • Marie-Michelle Simon

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • David Bujold

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • Tony Kwan

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • Guillaume Bourque

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • Avik Datta

    (European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus)

  • Ernesto Lowy

    (European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus)

  • Laura Clarke

    (European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus)

  • Paul Flicek

    (European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus)

  • Emanuele Libertini

    (Medical Genomics, UCL Cancer Institute, University College London)

  • Simon Heath

    (CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST)
    Universitat Pompeu Fabra, Plaça de la Mercè 10)

  • Marta Gut

    (CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST)
    Universitat Pompeu Fabra, Plaça de la Mercè 10)

  • Ivo G Gut

    (CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST)
    Universitat Pompeu Fabra, Plaça de la Mercè 10)

  • Willem H. Ouwehand

    (University of Cambridge, Cambridge Biomedical Campus
    National Health Service Blood and Transplant, Cambridge Biomedical Campus
    British Heart Foundation Centre of Excellence, Cambridge Biomedical Campus
    Human Genetics, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Tomi Pastinen

    (McGill University
    McGill University and Genome Quebec Innovation Centre)

  • Nicole Soranzo

    (University of Cambridge, Cambridge Biomedical Campus
    Human Genetics, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton)

  • Sabine E. Hofer

    (Medical University of Innsbruck)

  • Beate Karges

    (RWTH Aachen University
    German Center for Diabetes Research (DZD))

  • Thomas Meissner

    (German Center for Diabetes Research (DZD)
    Neonatology and Pediatric Cardiology, University Children’s Hospital, Heinrich Heine University of Düsseldorf)

  • Bernhard O. Boehm

    (Ulm University Medical Centre
    Lee Kong Chian School of Medicine, Nanyang Technological University
    Imperial College London)

  • Corrado Cilio

    (Lund University, Skåne University Hospital)

  • Helena Elding Larsson

    (Lund University, Skåne University Hospital)

  • Åke Lernmark

    (Lund University, Skåne University Hospital)

  • Andrea K. Steck

    (Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine)

  • Vardhman K. Rakyan

    (The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Stephan Beck

    (Medical Genomics, UCL Cancer Institute, University College London)

  • R. David Leslie

    (The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

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.

Suggested Citation

  • 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 & Sa, 2016. "Increased DNA methylation variability in type 1 diabetes across three immune effector cell types," Nature Communications, Nature, vol. 7(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13555
    DOI: 10.1038/ncomms13555
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    Cited by:

    1. Liam McAllan & Damir Baranasic & Sergio Villicaña & Scarlett Brown & Weihua Zhang & Benjamin Lehne & Marco Adamo & Andrew Jenkinson & Mohamed Elkalaawy & Borzoueh Mohammadi & Majid Hashemi & Nadia Fer, 2023. "Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Tianyu Zhu & Huige Tong & Zhaozhen Du & Stephan Beck & Andrew E. Teschendorff, 2024. "An improved epigenetic counter to track mitotic age in normal and precancerous tissues," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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