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. 2022 Apr 8;14(1):48.
doi: 10.1186/s13148-022-01269-9.

Epigenetics of early-life adversity in youth: cross-sectional and longitudinal associations

Jennifer A Sumner  1 , Simone Gambazza  2   3 , Xu Gao  4   5 , Andrea A Baccarelli  4 , Monica Uddin  6 , Katie A McLaughlin  7
Affiliations

Epigenetics of early-life adversity in youth: cross-sectional and longitudinal associations

Jennifer A Sumner et al. Clin Epigenetics. .

Abstract

Background: Altered DNA methylation (DNAm) may be one pathway through which early-life adversity (ELA) contributes to adverse mental and physical health outcomes. This study investigated whether the presence versus absence of ELA experiences reflecting the dimensions of threat and deprivation were associated with epigenome-wide DNAm cross-sectionally and longitudinally in a community-based sample of children and adolescents.

Methods: In 113 youths aged 8-16 years with wide variability in ELA, we examined associations of abuse (physical, sexual, emotional; indicating threat-related experiences) and neglect (emotional, physical; indicating deprivation-related experiences) with DNAm assessed with the Illumina EPIC BeadChip array, with DNA derived from saliva. In cross-sectional epigenome-wide analyses, we investigated associations of lifetime abuse and neglect with DNAm at baseline. In longitudinal epigenome-wide analyses, we examined whether experiencing abuse and neglect over an approximately 2-year follow-up were each associated with change in DNAm from baseline to follow-up.

Results: In cross-sectional analyses adjusting for lifetime experience of neglect, lifetime experience of abuse was associated with DNAm for four cytosine-phosphodiester-guanine (CpG) sites (cg20241299: coefficient = 0.023, SE = 0.004; cg08671764: coefficient = 0.018, SE = 0.003; cg27152686: coefficient = - 0.069, SE = 0.012; cg24241897: coefficient = - 0.003, SE = 0.001; FDR < .05). In longitudinal analyses, experiencing neglect over follow-up was associated with an increase in DNAm for one CpG site, adjusting for abuse over follow-up (cg03135983: coefficient = 0.036, SE = 0.006; FDR < .05).

Conclusions: In this study, we identified examples of epigenetic patterns associated with ELA experiences of threat and deprivation that were already observable in youth. We provide novel evidence for change in DNAm over time in relation to ongoing adversity and that experiences reflecting distinct ELA dimensions may be characterized by unique epigenetic patterns.

Keywords: Abuse; DNA methylation; Deprivation; Neglect; Threat.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Box plots of DNA methylation β-values for participants with and without lifetime abuse for four CpG sites uniquely associated with lifetime abuse in cross-sectional analyses, adjusting for lifetime neglect
See this image and copyright information in PMC

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References

    1. Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, Koss MP, Marks JS. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: the Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14:245–258. doi: 10.1016/S0749-3797(98)00017-8. - DOI - PubMed
    1. McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC. Childhood adversities and first onset of psychiatric disorders in a national sample of US adolescents. Arch Gen Psychiatry. 2012;69:1151–1160. doi: 10.1001/archgenpsychiatry.2011.2277. - DOI - PMC - PubMed
    1. McLaughlin KA. Future directions in childhood adversity and youth psychopathology. J Clin Child Adolesc Psychol. 2016;45:361–382. doi: 10.1080/15374416.2015.1110823. - DOI - PMC - PubMed
    1. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33:245–254. doi: 10.1038/ng1089. - DOI - PubMed
    1. Cecil CA, Zhang Y, Nolte T. Childhood maltreatment and DNA methylation: a systematic review. Neurosci Biobehav Rev. 2020;112:392–409. doi: 10.1016/j.neubiorev.2020.02.019. - DOI - PubMed

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