The immune factors driving DNA methylation variation in human blood

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, Darragh Duffy, Etienne Patin () and Lluís Quintana-Murci ()
Additional contact information
Jacob Bergstedt: Human Evolutionary Genetics Unit
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

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33511-6

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DOI: 10.1038/s41467-022-33511-6

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