Examining the epigenetic mechanisms of childhood adversity and sensitive periods: a gene set-based approach
Zhu, Yiwen; Lussier, Alexandre A; Smith, Andrew D A C; Simpkin, Andrew J; Suderman, Matthew J; Walton, Esther; Relton, Caroline L; Dunn, Erin C
Alexandre A Lussier
Andrew Smith Andrew18.Smith@uwe.ac.uk
Senior Lecturer in Statistics
Andrew J Simpkin
Matthew J Suderman
Caroline L Relton
Erin C Dunn
Background: Sensitive periods are developmental stages of heightened plasticity when life experiences, including exposure to childhood adversity, have the potential to exert more lasting impacts. Epigenetic mechanisms, including DNA methylation (DNAm), may provide a pathway through which adversity induces long-term biological changes. DNAm shifts may be more likely to occur during sensitive periods, especially within genes that regulate the timing of sensitive periods. Here, we investigated the possibility that childhood adversity during specific life stages is associated with DNAm changes in genes known to regulate the timing and duration of sensitive periods.
Methods: Genome-wide DNAm profiles came from the Avon Longitudinal Study of Parents and Children (n=785). We first used principal components analysis (PCA) to summarize DNAm variation across 530 CpG sites mapped to the promoters of 58 genes previously-identified as regulating sensitive periods. Gene-level DNAm summaries were calculated for genes regulating sensitive period opening (ngenes=15), closing (ngenes=36), and expression (ngenes=8). We then performed linear discriminant analysis (LDA) to test associations between seven types of parent-reported,
time-varying measures of exposure to childhood adversity and DNAm principal components. To our knowledge, this is the first time LDA has been applied to analyze functionally grouped DNAm data to characterize associations between an environmental exposure and epigenetic differences.
Results: Suggestive evidence emerged for associations between sexual or physical abuse as well as financial hardship during middle childhood, and DNAm of genetic pathways regulating sensitive period opening and expression. However, no statistically significant associations were identified after multiple testing correction.
Conclusions: Our gene set-based method combining PCA and LDA complements epigenome-wide approaches. Although our results were largely null, these findings provide a proof-of-concept
for studying time-varying exposures and gene- or pathway-level epigenetic modifications.
Zhu, Y., Lussier, A. A., Smith, A. D. A. C., Simpkin, A. J., Suderman, M. J., Walton, E., …Dunn, E. C. (in press). Examining the epigenetic mechanisms of childhood adversity and sensitive periods: a gene set-based approach. Psychoneuroendocrinology, Article 105854. https://doi.org/10.1016/j.psyneuen.2022.105854
|Journal Article Type||Article|
|Acceptance Date||Jun 25, 2022|
|Online Publication Date||Jun 27, 2022|
|Deposit Date||Jun 30, 2022|
|Publicly Available Date||Jun 28, 2023|
|Peer Reviewed||Peer Reviewed|
|Keywords||childhood adversity, sensitive periods, ALSPAC, plasticity, epigenetics|
This file is under embargo until Jun 28, 2023 due to copyright reasons.
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