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 were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53% of CpG sites) of CpG dinucleotides. In most cases DNAm was decreasing (36% of CpG sites). Inter-individual variation in linear trajectories was similarly widespread (27% of CpG sites). Evidence for nonlinear change and inter-individual variation in nonlinear trajectories was somewhat less common (11% and 8% of CpG sites, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpG sites) even though sex-specific DNAm was observed at 5% of CpG sites. 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, CpG sites 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.
Bibliographical notePublisher Copyright:
© The Author(s) 2021. Published by Oxford University Press.
- DNA methylation
- sex characteristics
- ALSPAC study