PT  - JOURNAL ARTICLE
AU  - Erin C. Dunn
AU  - Thomas W. Soare
AU  - Andrew J. Simpkin
AU  - Matthew J. Suderman
AU  - Yiwen Zhu
AU  - Torsten Klengel
AU  - Andrew D.A.C. Smith
AU  - Kerry Ressler
AU  - Caroline L. Relton
TI  - Sensitive periods for the effect of childhood adversity on DNA methylation: Results from a prospective, longitudinal study
AID  - 10.1101/271122
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 271122
4099  - http://biorxiv.org/content/early/2018/02/24/271122.short
4100  - http://biorxiv.org/content/early/2018/02/24/271122.full
AB  - Background Exposure to “early life” adversity is known to predict DNA methylation (DNAm) patterns that may be related to prolonged 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 (SLCMA), we tested the hypothesis that there are sensitive periods when adversity induced greater DNAm changes. We tested this hypothesis in relation to two alternative explanations: an accumulation hypothesis, in which the effect of adversity on DNAm 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 Epigenomics Studies (ARIES), a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC; n=670-776).Results After covariate adjustment and multiple testing correction, we identified 40 CpG sites that were differentially methylated at age 7 following exposure to adversity. Most loci (n=32) were predicted by the timing of adversity, namely exposures during infancy. Neither the accumulation nor recency of the adversity explained considerable variability in DNAm. A standard EWAS 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. Infancy appears to be a sensitive period when exposure to adversity predicts differential DNAm patterns. Classification of individuals as exposed vs. unexposed to “early life” adversity may dilute observed effects.