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An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

Author

Listed:
  • Jun Liu

    (Erasmus University Medical Center
    Nuffield Department of Population Health, University of Oxford)

  • Elena Carnero-Montoro

    (Erasmus University Medical Center
    GENYO, Pfizer/University of Granada/Andalusian Government, PTS
    King’s College London)

  • Jenny Dongen

    (Amsterdam UMC, Vrije Universiteit Amsterdam)

  • Samantha Lent

    (Boston University School of Public Health)

  • Ivana Nedeljkovic

    (Erasmus University Medical Center)

  • Symen Ligthart

    (Erasmus University Medical Center)

  • Pei-Chien Tsai

    (King’s College London
    Chang Gung University
    Chang Gung Memorial Hospital)

  • Tiphaine C. Martin

    (King’s College London
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Pooja R. Mandaviya

    (Erasmus University Medical Center)

  • Rick Jansen

    (Amsterdam UMC, Vrije Universiteit Amsterdam)

  • Marjolein J. Peters

    (Erasmus University Medical Center)

  • Liesbeth Duijts

    (Erasmus University Medical Center
    Erasmus University Medical Center)

  • Vincent W. V. Jaddoe

    (Erasmus University Medical Center
    Erasmus University Medical Center
    Erasmus University Medical Center)

  • Henning Tiemeier

    (Erasmus University Medical Center
    Harvard TH Chan School of Public Health)

  • Janine F. Felix

    (Erasmus University Medical Center
    Erasmus University Medical Center
    Erasmus University Medical Center)

  • Gonneke Willemsen

    (Amsterdam UMC, Vrije Universiteit Amsterdam)

  • Eco J. C. Geus

    (Amsterdam UMC, Vrije Universiteit Amsterdam)

  • Audrey Y. Chu

    (The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health
    The Framingham Heart Study, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Daniel Levy

    (The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health
    The Framingham Heart Study, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Shih-Jen Hwang

    (The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health
    The Framingham Heart Study, National Heart, Lung and Blood Institute, National Institutes of Health)

  • Jan Bressler

    (University of Texas Health Science Center at Houston)

  • Rahul Gondalia

    (University of North Carolina)

  • Elias L. Salfati

    (Stanford University School of Medicine)

  • Christian Herder

    (German Center for Diabetes Research (DZD)
    Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf
    Medical Faculty, Heinrich Heine University Düsseldorf)

  • Bertha A. Hidalgo

    (University of Alabama at Birmingham)

  • Toshiko Tanaka

    (Translational Gerontology Branch, National Institute on Aging)

  • Ann Zenobia Moore

    (Translational Gerontology Branch, National Institute on Aging)

  • Rozenn N. Lemaitre

    (Cardiovascular Health Research Unit, Department of Medicine, University of Washington)

  • Min A Jhun

    (School of Public Health, University of Michigan)

  • Jennifer A. Smith

    (School of Public Health, University of Michigan)

  • Nona Sotoodehnia

    (Cardiovascular Health Research Unit, Department of Medicine, University of Washington)

  • Stefania Bandinelli

    (Azienda Sanitaria di Firenze)

  • Luigi Ferrucci

    (Translational Gerontology Branch, National Institute on Aging)

  • Donna K. Arnett

    (University of Kentucky)

  • Harald Grallert

    (German Center for Diabetes Research (DZD)
    Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health)

  • Themistocles L. Assimes

    (Stanford University School of Medicine)

  • Lifang Hou

    (Northwestern University Chicago
    Feinberg School of Medicine, Northwestern University)

  • Andrea Baccarelli

    (Mailman School of Public Health, Columbia University)

  • Eric A. Whitsel

    (University of North Carolina
    University of North Carolina School of Medicine, Chapel Hill)

  • Ko Willems Dijk

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Najaf Amin

    (Erasmus University Medical Center)

  • André G. Uitterlinden

    (Erasmus University Medical Center
    Erasmus University Medical Center)

  • Eric J. G. Sijbrands

    (Erasmus University Medical Center)

  • Oscar H. Franco

    (Erasmus University Medical Center
    Institute of Social and Preventive Medicine (ISPM), University of Bern)

  • Abbas Dehghan

    (Erasmus University Medical Center
    Imperial College London)

  • Tim D. Spector

    (King’s College London)

  • Josée Dupuis

    (Boston University School of Public Health)

  • Marie-France Hivert

    (Université de Sherbrooke
    Massachusetts General Hospital
    Harvard Medical School and Harvard Pilgrim Health Care Institute)

  • Jerome I. Rotter

    (The Institute for Translational Genomics and Population Sciences and Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center)

  • James B. Meigs

    (Harvard Medical School
    Massachusetts General Hospital
    Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard)

  • James S. Pankow

    (University of Minnesota)

  • Joyce B. J. Meurs

    (Maastricht University)

  • Aaron Isaacs

    (Erasmus University Medical Center
    Maastricht University)

  • Dorret I. Boomsma

    (Amsterdam UMC, Vrije Universiteit Amsterdam)

  • Jordana T. Bell

    (King’s College London)

  • Ayşe Demirkan

    (Erasmus University Medical Center
    University Medical Center Groningen
    Univeristy of Surrey)

  • Cornelia M. Duijn

    (Erasmus University Medical Center
    Nuffield Department of Population Health, University of Oxford
    Leiden University)

Abstract

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.

Suggested Citation

  • Jun Liu & Elena Carnero-Montoro & Jenny Dongen & Samantha Lent & Ivana Nedeljkovic & Symen Ligthart & Pei-Chien Tsai & Tiphaine C. Martin & Pooja R. Mandaviya & Rick Jansen & Marjolein J. Peters & Lie, 2019. "An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10487-4
    DOI: 10.1038/s41467-019-10487-4
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