The immune factors driving DNA methylation variation in human blood

• Published in: Nature communications Vol. 13; no. 1; pp. 5895 - 20
• Main Authors: Bergstedt, Jacob, Azzou, Sadoune Ait Kaci, Tsuo, Kristin, Jaquaniello, Anthony, Urrutia, Alejandra, Rotival, Maxime, Lin, David T. S., MacIsaac, Julia L., Kobor, Michael S., Albert, Matthew L., Duffy, Darragh, Patin, Etienne, Quintana-Murci, Lluís
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/22; 45/43; 49; 49/61; 631/208/176/1988; 631/208/177; 631/250/2502/2170; Adult; Adults; Aging; Aging - genetics; Blood; Composition; Cytomegalovirus; Deoxyribonucleic acid; DNA; DNA Methylation; Epigenesis, Genetic; Epigenetics; Epigenomics - methods; Gene sequencing; Humanities and Social Sciences; Humans; Immunologic Factors; Immunological memory; Immunology; Leukocytes; Life Sciences; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Memory cells; multidisciplinary; Nucleotide sequence; Science; Science (multidisciplinary); Variation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-33511-6

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. Many studies assess epigenetic marks in white blood cells, but it is unclear how much immune factors affect the epigenome. Here, the authors show that fine-scale blood cell composition and cytomegalovirus infection affect the DNA methylome of adults.