Examining the epigenetic mechanisms of childhood adversity and sensitive periods: A gene set-based approach.
ALSPAC
Childhood adversity
Epigenetics
Plasticity
Sensitive periods
Journal
Psychoneuroendocrinology
ISSN: 1873-3360
Titre abrégé: Psychoneuroendocrinology
Pays: England
ID NLM: 7612148
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
03
09
2021
revised:
24
06
2022
accepted:
24
06
2022
pubmed:
2
8
2022
medline:
9
9
2022
entrez:
1
8
2022
Statut:
ppublish
Résumé
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. Genome-wide DNAm profiles came from the Avon Longitudinal Study of Parents and Children (n = 785). We first used principal component 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 (n 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. 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.
Sections du résumé
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 component 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 (n
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.
Identifiants
pubmed: 35914392
pii: S0306-4530(22)00195-0
doi: 10.1016/j.psyneuen.2022.105854
pmc: PMC9885844
mid: NIHMS1867894
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
105854Subventions
Organisme : Medical Research Council
ID : MC_UU_00011/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : R01 HD068437
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBI025751/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI121226
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12013/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 217065/ Z/19/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH113930
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/I025263/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/8
Pays : United Kingdom
Organisme : Medical Research Council
ID : MRC_UU_ 00011/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Informations de copyright
Copyright © 2022 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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