Lookup NU author(s): Professor Caroline Relton
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© 2019 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.
Author(s): Dunn EC, Soare TW, Zhu Y, Simpkin AJ, Suderman MJ, Klengel T, Smith ADAC, Ressler KJ, Relton CL
Publication type: Article
Publication status: Published
Journal: Biological Psychiatry
Print publication date: 15/05/2019
Online publication date: 21/01/2019
Acceptance date: 16/12/2018
ISSN (print): 0006-3223
ISSN (electronic): 1873-2402
Publisher: Elsevier USA
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