Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence

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 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 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.

Epigenome-wide association study of left-handedness for different tissues and ages

“…Therefore, DNA methylation differences associated with hand preference are expected to emerge early in development. While DNA methylation at some CpGs in the genome changes throughout the lifespan 55 , the DNA methylation signal associated with left-handedness was moderately consistent from birth throughout the lifespan: DMP effect sizes were correlated in ALSPAC individuals from birth to 24 years old, although genome-wide signi cance for DMPs was not reached. Consistency in DNA methylation signal associated with left-handedness at different time-points may indicate that the pattern for lefthandedness is conserved through the lifespan.…”

“…While handedness is a stable trait, DNA methylation can vary over time 55 . We analyzed DNA methylation in ALSPAC offspring measured in cord blood at birth, and in peripheral blood at 7, 17, and 24 years old (N~1021, Table 2 and Table S2) to examine the association between DNA methylation and left-handedness throughout childhood and adolescence.…”

Epigenome-wide contributions to individual differences in childhood phenotypes: A GREML approach

“…Quality control exclusion criteria included failed bisulfite conversion, hybridization or extension, sex mismatches and call rate <= 95%. Both cohorts were normalized using a combined dataset, using meffil functional normalization with ten control probe principal components and slide included as a random effect, see Mulder et al (21) for further details. To lessen the influence of methylation outliers while retaining a consistent sample size, extreme values were winsorized.…”

Sex-specific longitudinal association of DNA methylation with lung function

“…DNA-M changes over time at specific CpGs [ 19 , 20 ], and such changes have been shown to be sex-specific [ 20 , 21 ]. Changes in DNA-M can occur in response to biological ageing, but also to environmental exposures [ 22 ].…”