1. Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo
- Author
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Maria Derakhshan, Noah J Kessler, Miho Ishida, Charalambos Demetriou, Nicolas Brucato, Gudrun E Moore, Caroline H D Fall, Giriraj R Chandak, Francois-Xavier Ricaut, Andrew M Prentice, Garrett Hellenthal, Matt J Silver, Evolution et Diversité Biologique (EDB), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Medical Research Council, Human Genetics Division [Singapore], Genome Institute of Singapore (GIS), and University College of London [London] (UCL)
- Subjects
Tissue-and ethnicity-independent ,Illumina 450K array ,Hypervariable DNA methylation ,Genetics ,Early embryo ,Humans ,Reproducibility of Results ,Systemic inter-individual variation ,[SDE.BE]Environmental Sciences/Biodiversity and Ecology ,DNA Methylation - Abstract
We analysed DNA methylation data from 30 datasets comprising 3474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4143 hypervariable CpGs (‘hvCpGs’) with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by genetic variation, and was not linked to probe reliability, epigenetic drift, age, sex or cell heterogeneity effects. hvCpG methylation tended to covary across tissues derived from different germ-layers and hvCpGs were enriched for proximity to ERV1 and ERVK retrovirus elements. hvCpGs were also enriched for loci previously associated with periconceptional environment, parent-of-origin-specific methylation, and distinctive methylation signatures in monozygotic twins. Together, these properties position hvCpGs as strong candidates for studying how stochastic and/or environmentally influenced DNA methylation states which are established in the early embryo and maintained stably thereafter can influence life-long health and disease.
- Published
- 2022