Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France.
Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Nat Commun. 2022 Oct 6;13(1):5895. 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.
表观遗传变化是正常发育所必需的，但驱动人类表观遗传变异的因素的性质及其各自的贡献仍有待充分描述。在这里，我们评估了 884 名成年人的血液 DNA 甲基化组如何受到 DNA 序列变异、年龄、性别以及与生活习惯和免疫相关的 139 个因素的影响。此外，我们还研究了这些影响是否通过深度免疫表型测量的细胞组成变化来介导。我们表明，幼稚 T 细胞和记忆 T 细胞之间的 DNA 甲基化有很大差异，这支持了需要针对这些细胞类型进行调整的观点。通过这样做，我们发现潜伏性巨细胞病毒感染会驱动 DNA 甲基化变异，并进一步表明随着年龄的增长 DNA 甲基化的分散增加是由于表观遗传漂移所致。最后，我们的结果表明，细胞组成和 DNA 序列变异是 DNA 甲基化的最强预测因子，突出了医学表观基因组学研究的关键因素。
