Publication date: Aug 2023
What is already known about this subject:
- Childhood adversity, such as poverty and abuse, is a strongly linked to poorer physical and mental health across development. However, the biological mechanisms explaining how these stressful life experiences exposure creates this increase long-term vulnerability to disease are poorly understood. One possibility is that exposure to stress reexposure programs the epigenome biological systems through DNA methylation marks, which are chemical changes to DNA that can influence gene expression without that do not alter changing the DNA sequence but that can influence gene expression. In other words, life experiences such as childhood adversity could leave lasting "biological memories” on the genome, which might explain their impact on health outcomes.
- Recent evidence also suggests that the effects of childhood adversity on these DNA methylation epigenetic patterns is stronger when it occurs during “sensitive periods”, , meaning times during development when children may be more vulnerable to adverse life experiences. However, it remains unclear if the effects of childhood adversity during these sensitive periods on the epigenome are temporary, or whether if they persist across development from childhood to adolescence.
- By determining when and how childhood adversity influences DNA methylation patterns, we may be able to better target interventions that prevent the effects of childhood adversity, as well as predict who might be at higher risk for the negative health outcomes linked to these adverse life experiences.
- Thus, our aims were to: 1) determine whether there are sensitive periods that explain the relationship between childhood adversity and adolescent DNA methylation is influenced by the timing of adversity; 2) characterize identify the trajectories of DNA methylation across childhood and adolescence that are linked to childhood adversity; and 3) evaluate whether previously-identified links between childhood adversity and DNA methylation in childhood persist into adolescence.
What this study adds
- Primary sample: We used data from the Avon Longitudinal Study of Parents and Children in our primary analyses of time-varying childhood adversity and epigenome-wide DNA methylation (DNAm) at ages 7 and 15. We investigated seven types of childhood adversity, which captured experiences of sexual/physical abuse, financial hardship, family instability, maternal psychopathology, one-adult households, neighborhood disadvantage, and caregiver physical/emotional abuse. These adversities were each measured 5-8 times between birth and age 11, while genome-wide DNAm patterns were collected from blood at ages 7 and 15.
- Replication sample: We replicated main associations between exposures to one-adult households and DNAm at age 15 using data from the Raine Study. Briefly, we investigated measures of one adult households between ages 0-12 and epigenome-wide DNA methylation levels collected from blood at age 17.
- Methods: In the ALSPAC cohort, we first investigated the relationship between the timing of exposure to seven types of adversity and DNAm in blood at age 15 using a structured life course modeling approach (SLCMA). We also assessed the persistence of adversity-DNAm associations identified from age 7 blood DNAm into adolescence and the influence of adversity on DNAm trajectories from ages 0-15 in ALSPAC.
- Findings: Adversity exposure was associated with differences in age 15 DNAm at 41 loci (R2≥0.035; p<1x10-5; 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; DNAm differences at age 15 were not present in age 7 DNAm. We also identified six distinct DNAm trajectories that highlighted both immediate and latent associations with adversity. Associations were robust in internal validation analyses using nonparametric bootstrapping. We also partially replicated associations between exposures to one-adult households and adolescent DNAm levels, showing similarities between the timing of exposures and direction of associations for the majority of loci.
- Significance: These findings highlight the immediate and latent impact of childhood adversity on DNAm, providing a potential biological mechanism linking adversity to adverse physical and mental health outcomes in children and adolescents.