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The immune factors driving DNA methylation variation in human blood

Author

Listed:
  • Jacob Bergstedt

    (Human Evolutionary Genetics Unit
    Karolinska Institutet
    Karolinska Institutet)

  • Sadoune Ait Kaci Azzou

    (Human Evolutionary Genetics Unit)

  • Kristin Tsuo

    (Human Evolutionary Genetics Unit)

  • Anthony Jaquaniello

    (Human Evolutionary Genetics Unit)

  • Alejandra Urrutia

    (HI-Bio)

  • Maxime Rotival

    (Human Evolutionary Genetics Unit)

  • David T. S. Lin

    (University of British Columbia)

  • Julia L. MacIsaac

    (University of British Columbia)

  • Michael S. Kobor

    (University of British Columbia)

  • Matthew L. Albert

    (HI-Bio)

  • Darragh Duffy

    (Institut Pasteur, Université Paris Cité, Translational Immunology Unit, Institut Pasteur)

  • Etienne Patin

    (Human Evolutionary Genetics Unit)

  • Lluís Quintana-Murci

    (Human Evolutionary Genetics Unit
    Collège de France)

Abstract

Epigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how the blood DNA methylome of 884 adults is affected by DNA sequence variation, age, sex and 139 factors relating to life habits and immunity. Furthermore, we investigated whether these effects are mediated or not by changes in cellular composition, measured by deep immunophenotyping. We show that DNA methylation differs substantially between naïve and memory T cells, supporting the need for adjustment on these cell-types. By doing so, we find that latent cytomegalovirus infection drives DNA methylation variation and provide further support that the increased dispersion of DNA methylation with aging is due to epigenetic drift. Finally, our results indicate that cellular composition and DNA sequence variation are the strongest predictors of DNA methylation, highlighting critical factors for medical epigenomics studies.

Suggested Citation

  • Jacob Bergstedt & Sadoune Ait Kaci Azzou & Kristin Tsuo & Anthony Jaquaniello & Alejandra Urrutia & Maxime Rotival & David T. S. Lin & Julia L. MacIsaac & Michael S. Kobor & Matthew L. Albert & Darrag, 2022. "The immune factors driving DNA methylation variation in human blood," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33511-6
    DOI: 10.1038/s41467-022-33511-6
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    References listed on IDEAS

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