A prospective study of time-dependent childhood adversity and DNA methylation across childhood and adolescence

ABSTRACT Background Children exposed to adversity often have epigenetic profiles, including DNA methylation (DNAm) signatures, that differ from children without adversity histories. These signatures may be more common among children exposed during sensitive periods in development. However, it remains unclear if adversity has persistent (versus transient) effects on the epigenome across childhood and adolescence. Thus, we examined the relationship between time-varying adversity and genome-wide DNAm, measured three times from birth to adolescence using prospective data from the Avon Longitudinal Study of Parents and Children. Methods We first investigated 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 (SLCMA). We also assessed the persistence of adversity-DNAm associations identified from age 7 DNAm into adolescence and the influence of adversity on DNAm trajectories from ages 0-15. Results Adversity exposure was associated with differences in age 15 DNAm at 41 loci (R 2 ≥0.035; p<1×10 −5 ; 22 at FDR<0.05). Most loci were associated with adversities (i.e., physical, sexual, or emotional abuse; one-adult households) occurring between ages 3-5. DNAm differences present at age 7 resolved by adolescence; age 15 differences were not apparent in childhood. We also identified six distinct DNAm trajectories that highlighted both immediate and latent effects of adversity. Associations were robust in internal validation analyses using nonparametric bootstrapping. Conclusions These findings highlight the immediate and latent effects of childhood adversity on DNAm, providing a potential biological mechanism linking adversity to physical and mental health outcomes across development.