The immune factors driving DNA methylation variation in human blood
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Published:2022-10-06
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Bergstedt JacobORCID, Azzou Sadoune Ait KaciORCID, Tsuo KristinORCID, Jaquaniello Anthony, Urrutia Alejandra, Rotival MaximeORCID, Lin David T. S., MacIsaac Julia L., Kobor Michael S.ORCID, Albert Matthew L.ORCID, Duffy DarraghORCID, Patin EtienneORCID, Quintana-Murci LluísORCID, Abel Laurent, Alcover Andres, Aschard Hugues, Bousso Philippe, Bourke Nollaig, Brodin Petter, Bruhns Pierre, Cerf-Bensussan Nadine, Cumano Ana, d’Enfert Christophe, Deriano Ludovic, Dillies Marie-Agnès, Di Santo James, Dromer Françoise, Eberl Gérard, Enninga Jost, Fellay Jacques, Gomperts-Boneca Ivo, Hasan Milena, Hedestam Gunilla Karlsson, Hercberg Serge, Ingersoll Molly A., Lantz Olivier, Kenny Rose Anne, Ménager Mickaël, Michel Frédérique, Mouquet Hugo, O’Farrelly Cliona, Pellegrini Sandra, Rausell Antonio, Rieux-Laucat Frédéric, Rogge Lars, Fontes Magnus, Sakuntabhai Anavaj, Schwartz Olivier, Schwikowski Benno, Shorte Spencer, Tangy Frédéric, Toubert Antoine, Touvier Mathilde, Ungeheuer Marie-Noëlle, Zimmer Christophe, Quintana-Murci Lluis,
Abstract
AbstractEpigenetic 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference121 articles.
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