A prospective study of time-dependent exposures to childhood adversity and DNA methylation in childhood and adolescence
Background: Childhood adversity influences long-term health, particularly if experienced during sensitive periods in development when physiological systems are more responsive to environmental influences. Although the underlying mechanisms remain unclear, prior studies suggest that DNA methylation (DNAm) may capture these time-dependent effects of childhood adversity. However, it remains unknown whether DNAm alterations persist into adolescence and how the timing of adversity might influence DNAm trajectories across development. Methods: We examined the relationship between time-dependent adversity and genome-wide DNAm measured at three waves from birth to adolescence using prospective data from the Avon Longitudinal Study of Parents and Children. We first assessed the relationship between the timing of exposure to seven types of adversity (measured 5-8 times between ages 0-11) and DNAm at age 15 using a structured life course modeling approach. We also characterized the persistence into adolescence of associations identified from age 7 DNAm, as well as the influence of adversity on DNAm trajectories from ages 0-15. Results: Adversity was associated with differences in age 15 DNAm at 24 loci (FDR<0.05). Most loci (19 of 24) were associated with adversity (i.e., physical/sexual abuse, one-adult households, caregiver abuse) that occurred between ages 3-5. Although no DNAm differences present at age 7 persisted into adolescence, we identified seven unique types of DNAm trajectories across development, which highlighted diverse effects of childhood adversity on DNAm. Conclusions: Our results suggest that childhood adversity, particularly between ages 3-5, can influence the trajectories of DNAm across development, exerting both immediate and latent effects on the epigenome.