Abstract
Background
Exposure to early-life adversity is known to predict DNA methylation (DNAm) patterns
that may be related to psychiatric risk. However, few studies have investigated whether
adversity has time-dependent effects based on the age at exposure.
Methods
Using a two-stage structured life course modeling approach, we tested the hypothesis
that there are sensitive periods when adversity induces greater DNAm changes. We tested
this hypothesis in relation to two alternatives: an accumulation hypothesis, in which
the effect of adversity increases with the number of occasions exposed, regardless
of timing; and a recency model, in which the effect of adversity is stronger for more
proximal events. Data came from the Accessible Resource for Integrated Epigenomic
Studies, a subsample of mother–child pairs from the Avon Longitudinal Study of Parents
and Children (n = 691–774).
Results
After covariate adjustment and multiple testing correction, we identified 38 CpG sites
that were differentially methylated at 7 years of age following exposure to adversity.
Most loci (n = 35) were predicted by the timing of adversity, namely exposures before 3 years
of age. Neither the accumulation nor recency of the adversity explained considerable
variability in DNAm. A standard epigenome-wide association study of lifetime exposure
(vs. no exposure) failed to detect these associations.
Conclusions
The developmental timing of adversity explains more variability in DNAm than the accumulation
or recency of exposure. Very early childhood appears to be a sensitive period when
exposure to adversity predicts differential DNAm patterns. Classification of individuals
as exposed versus unexposed to early-life adversity may dilute observed effects.
Keywords
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Article Info
Publication History
Published online: January 21, 2019
Accepted:
December 16,
2018
Received in revised form:
December 4,
2018
Received:
February 28,
2018
Identification
Copyright
© 2019 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.
