Objective
DNA methylation has been proposed as an epigenetic mechanism by which
early-life experiences become “embedded” in the genome and
alter transcriptional processes to compromise health. The authors sought to
investigate whether early-life victimization stress is associated with
genome-wide DNA methylation.
Method
The authors tested the hypothesis that victimization is associated
with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study,
a nationally representative 1994–1995 birth cohort of 2,232 twins
born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years.
Multiple forms of victimization were ascertained in childhood and
adolescence (including physical, sexual, and emotional abuse; neglect;
exposure to intimate-partner violence; bullying; cyber-victimization; and
crime).
Results
Epigenome-wide analyses of polyvictimization across childhood and
adolescence revealed few significant associations with DNA methylation in
peripheral blood at age 18, but these analyses were confounded by tobacco
smoking and/or did not survive co-twin control tests. Secondary analyses of
specific forms of victimization revealed sparse associations with DNA
methylation that did not replicate across different operationalizations of
the same putative victimization experience. Hypothesis-driven analyses of
six candidate genes in the stress response (NR3C1, FKBP5,
BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted
associations with DNA methylation in probes annotated to these genes.
Conclusions
Findings from this epidemiological analysis of the epigenetic effects
of early-life stress do not support the hypothesis of robust changes in DNA
methylation in victimized young people. We need to come to terms with the
possibility that epigenetic epidemiology is not yet well matched to
experimental, nonhuman models in uncovering the biological embedding of
stress.