Evidence map›Paper›PMID 27898055›Full record

ArticleNature communications2016

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

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 and 35 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
20.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. International journal of molecular medicine · 2026
    Review
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  7. Article
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  15. On epigenetic stochasticity, entropy and cancer risk.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

45 authors at 14 institutions in 9 countries.

Dirk S PaulMedical Genomics, UCL Cancer Institute, University College London, London WC1E 6BT, UK.ORCID 0000-0002-8230-0116
Andrew E TeschendorffCAS Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Mary A N DangThe Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Robert LoweThe Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Mohammed I HawaThe Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Simone EckerMedical Genomics, UCL Cancer Institute, University College London, London WC1E 6BT, UK.
Huriya BeyanThe Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Stephanie CunninghamThe Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Alexandra R FoutsBarbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
Anita RameliusDepartment of Clinical Sciences, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
Frances BurdenDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Samantha FarrowDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Sophia RowlstonDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Karola RehnstromDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Mattia FrontiniDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0001-8074-6299
Kate DownesDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Stephan BuscheDepartment of Human Genetics, McGill University, Montreal, Québec, Canada H3A 0G1.
Warren A CheungDepartment of Human Genetics, McGill University, Montreal, Québec, Canada H3A 0G1.
Bing GeDepartment of Human Genetics, McGill University, Montreal, Québec, Canada H3A 0G1.
Marie-Michelle SimonDepartment of Human Genetics, McGill University, Montreal, Québec, Canada H3A 0G1.
David BujoldDepartment of Human Genetics, McGill University, Montreal, Québec, Canada H3A 0G1.
Tony KwanDepartment of Human Genetics, McGill University, Montreal, Québec, Canada H3A 0G1.
Guillaume BourqueDepartment of Human Genetics, McGill University, Montreal, Québec, Canada H3A 0G1.
Avik DattaEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Ernesto LowyEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Laura ClarkeEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.ORCID 0000-0002-5989-6898
Paul FlicekEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.ORCID 0000-0002-3897-7955
Emanuele LibertiniMedical Genomics, UCL Cancer Institute, University College London, London WC1E 6BT, UK.
Simon HeathCNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 4, 08028 Barcelona, Spain.ORCID 0000-0002-9550-0897
Marta GutCNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 4, 08028 Barcelona, Spain.
Ivo G GutCNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 4, 08028 Barcelona, Spain.
Willem H OuwehandDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
Tomi PastinenDepartment of Human Genetics, McGill University, Montreal, Québec, Canada H3A 0G1.
Nicole SoranzoDepartment of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.ORCID 0000-0003-1095-3852
Sabine E HoferDepartment of Pediatrics, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Beate KargesDivision of Endocrinology and Diabetes, RWTH Aachen University, 52074 Aachen, Germany.
Thomas MeissnerGerman Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Bernhard O BoehmDivision of Endocrinology, Department of Internal Medicine I, Ulm University Medical Centre, 89081 Ulm, Germany.
Corrado CilioDepartment of Clinical Sciences, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
Helena Elding LarssonDepartment of Clinical Sciences, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
Åke LernmarkDepartment of Clinical Sciences, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
Andrea K SteckBarbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
Vardhman K RakyanThe Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Stephan BeckMedical Genomics, UCL Cancer Institute, University College London, London WC1E 6BT, UK.ORCID 0000-0001-5290-2151
R David LeslieThe Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
McGill Genome Centre · CANational Health Service · GBQueen Mary University of London · GBEuropean Bioinformatics Institute · GBLund University · SEUniversitat Pompeu Fabra · ESUniversity College London · GBUniversity of Cambridge · GBUniversity of Colorado Health · USChinese Academy of Sciences · CNDeutsches Diabetes-Zentrum e.V. · DEDüsseldorf University Hospital · DEInnsbruck Medical University · ATNanyang Technological University · SG

Funding

British Heart Foundation RG/09/012/28096Department of Health RP-PG-0310-1002Medical Research Council G0800270Wellcome Trust
6 · The paper itself

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.

Indexed as

CpG IslandsDiabetes Mellitus, Type 1DNA MethylationFetal BloodHumansMolecular Sequence AnnotationTime FactorsTwins, Monozygotic

Identifiers

PMID27898055
PMCPMC5141286
OpenAlexW2557683813

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.