Contributors: Génétique Evolutive Humaine - Human Evolutionary Genetics; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); The Institute of Environmental Medicine Stockholm (IMM); Karolinska Institutet Stockholm; HIBIO South San Francisco; University of British Columbia (UBC); Immunologie Translationnelle - Translational Immunology lab; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Collège de France - Chaire Génomique humaine et évolution; Collège de France (CdF (institution)); This work benefited from support of the French government’s program ‘Investissement d’Avenir’, managed by the Agence Nationale de la Recherche (reference 10-LABX-69-01).; Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Philippe Bousso, Nollaig Bourke, Petter Brodin, Pierre Bruhns, Nadine Cerf-Bensussan, Ana Cumano, Christophe d’Enfert, Ludovic Deriano, Marie-Agnès Dillies, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Gunilla Karlsson Hedestam, Serge Hercberg, Molly A. Ingersoll, Olivier Lantz, Rose Anne Kenny, Mickaël Ménager, Frédérique Michel, Hugo Mouquet, Cliona O’Farrelly, Etienne Patin, Sandra Pellegrini, Antonio Rausell, Frédéric Rieux-Laucat, Lars Rogge, Magnus Fontes, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Christophe Zimmer, Matthew L. Albert, Darragh Duffy & Lluis Quintana-Murci; We thank Sarah Merrill, Nicole Gladish, Violaine Saint-André, Lucas Husquin and the Milieu Intérieur scientific advisory board for comments and helpful discussions. We acknowledge the help of the HPC Core Facility of Institut Pasteur for this work.This research was enabled, in part, by the use of the FlowSorted.BloodExtended.EPIC R package developed at Dartmouth College, which software is subject to the licensing terms made available by Dartmouth Technology Transfer and which software is provided “as is” with no warranties whatsoever.; ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010)
نبذة مختصرة : International audience ; 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.
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