The immune factors driving DNA methylation variation in human blood.

Autor: Bergstedt J; Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France. jacob.bergstedt@ki.se.; Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. jacob.bergstedt@ki.se.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. jacob.bergstedt@ki.se., Azzou SAK; Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France., Tsuo K; Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France., Jaquaniello A; Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France., Urrutia A; HI-Bio, South San Francisco, CA, USA., Rotival M; Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France., Lin DTS; Edwin S.H. Leong Healthy Aging Program, Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, Canada., MacIsaac JL; Edwin S.H. Leong Healthy Aging Program, Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Kobor MS; Edwin S.H. Leong Healthy Aging Program, Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Albert ML; HI-Bio, South San Francisco, CA, USA., Duffy D; Institut Pasteur, Université Paris Cité, Translational Immunology Unit, Institut Pasteur, Paris, France., Patin E; Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France. epatin@pasteur.fr., Quintana-Murci L; Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France. quintana@pasteur.fr.; Chair of Human Genomics and Evolution, Collège de France, Paris, France. quintana@pasteur.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 06; Vol. 13 (1), pp. 5895. Date of Electronic Publication: 2022 Oct 06.
DOI: 10.1038/s41467-022-33511-6
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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