Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity

Abstract

Internationally-adopted adolescents who are adopted as young children conditions of poverty and deprivation have poorer physical and mental health outcomes than adolescents conceived, born and raised in the US by families similar to those who adopt internationally. Using a sample of Russian and Eastern European adoptees to control for Caucasian race and US born, non-adopted offspring of well-educated and well-resourced parents to control for post-adoption conditions, we hypothesized that the important differences in environments, conception to adoption, might be reflected in epigenetic patterns between groups, specifically in DNA methylation. Thus, we conducted an epigenome-wide association study (EWAS) to compare DNA methylation profiles at approximately 416,000 individual CpG loci from peripheral blood mononuclear cells of 50 adopted youth and 33 non-adopted youth. Adopted youth averaged 22 months at adoption and both groups averaged 15 years at testing, thus roughly 80% of their lives were lived in similar circumstances. Although concurrent physical health did not differ, cell type composition predicted using the DNA methylation data revealed a striking difference in the white blood cell type composition of the adopted and non-adopted youth. After correcting for cell type and removing invariant probes, 30 CpG sites in 19 genes were more methylated in the adopted group. We also used an exploratory functional analysis that revealed that 223 Gene Ontology (GO) terms, clustered in neural and developmental categories, were significantly enriched between groups.

Analysis of DNA Methylation in Young People: Limited Evidence for an Association Between Victimization Stress and Epigenetic Variation in Blood

“…Although most victimization experiences peak in adolescence, it has been hypothesized that the most biologically consequential victimization is experienced earlier in life (38). However, no probes passed the array-wide significance threshold in a regression model of childhood polyvictimization (Figure 3).…”

Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression

“…A foundational discovery in this area was the demonstration that early life experiences could be inscribed on the genome via methylation of CpG dinucleotides, and thereby affect personality and behavior in adulthood 18,19 . Since that demonstration, human and animal evidence has accumulated supporting alterations in patterns of DNA methylation as a link between early life adversity and adult psychopathology [20][21][22][23][24] .…”

Annual Research Review: DNA methylation as a mediator in the association between risk exposure and child and adolescent psychopathology

“…Blood samples were taken between 7 and 10 years of age and DNAm was assessed with the Illumina 27k. In another study, Esposito et al (2016) examined epigenome-wide DNAm (whole blood; Illumina 450k) in a sample of Russian and Eastern European adopted children (n = 50) compared with matched nonadopted children (n = 33). The authors identified 30 differentially methylated sites spanning 19 genes enriched for neural development and developmental biology.…”