1. Epigenome-wide change and variation in DNA methylation from birth to late adolescence
- Author
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Lotte C Houtepen, Tom R. Gaunt, Henning Tiemeier, Andrew J Simpkin, Cecil Cam, Janine F. Felix, Jolien Rijlaarsdam, Alexander Neumann, van IJzendoorn Mh, Jaddoe Vwv., Rosa H. Mulder, Caroline L Relton, Bastiaan T. Heijmans, Esther Walton, Matthew Suderman, and Marian J. Bakermans-Kranenburg
- Subjects
0303 health sciences ,dNaM ,Disease ,Epigenome ,Biology ,Genome ,03 medical and health sciences ,0302 clinical medicine ,CpG site ,Evolutionary biology ,DNA methylation ,human activities ,Gene ,030217 neurology & neurosurgery ,030304 developmental biology ,Genetic association - Abstract
DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5,019 blood samples collected at multiple time-points from birth to late adolescence from 2,348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for nonlinear change and inter-individual variation in nonlinear trajectories was somewhat less common (11% and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. By contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often nonlinear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.
- Published
- 2020
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