Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

Research Article

Marilyn J. Essex1, W. Tom Boyce2, Clyde Hertzman2, Lucia L. Lam3, Jeffrey M. Armstrong1, Sarah M. Neumann3 and Michael S. Kobor3

1 Department of Psychiatry, University of Wisconsin School of Medicine and Public Health
2 Human Early Learning Partnership, University of British Columbia
3 Centre for Molecular Medicine and Therapeutics, University of British Columbia

Link to full article in Child Development

Abstract

Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents’ infancy and preschool periods. Microarray technology applied to 28,000 cytosine–guanine dinucleotide sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children’s early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children’s gender. To the authors’ knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents’ genomic DNA.

Supplementary Tables

Figure S1 DNA methylation at a CpG site in the promoter of the MGMT gene was correlated with paternal stress during infancy in girls only.

Figure S2 DNA methylation at two CpG sites in the first exon of the c19orf30 gene was correlated with paternal stress during preschool in girls only.

Figure S3 DNA methylation at three CpG sites in the MGC33302 gene (also known as MFSD8/CLN7) was correlated with paternal stress during preschool in girls only.

Table S1 Correlation between maternal stress during infancy and increased DNA methylation in adolescence in full sample (all CpG sites with FDR <20%). Sites with greater than 5% differential methylation are highlighted in gray.

Table S2 Correlation between paternal stress during preschool and increased DNA methylation in adolescence in full sample (all CpG sites with FDR <20%). Sites with greater than 5% differential methylation are highlighted in gray.

Table S3 Correlation of parental stress during infancy and preschool with DNA methylation levels of selected candidate genes. FDR corresponds to the multiple testing correction applied to the entire data set (n = 18,231).

  1. NR3C1   Glucocorticoid receptor
  2. DRD4   Dopamine receptor D4
  3. SLC6A4/5HTT   Solute carrier family 6 (neurotransmitter transporter, serotonin), member 4
  4. BDNF   Brain-derived neurotrophic factor
  5. BDNF   Brain-derived neurotrophic factor
  6. COMT   Catechol-O-methyltransferase
  7. SLC6A3/DAT1   Solute carrier family 6 (neurotransmitter transporter, dopamine), member 3
  8. SLC6A3/DAT1   Solute carrier family 6 (neurotransmitter transporter, dopamine), member 3

Table S4 Correlation between maternal stress during infancy and increased DNA methylation in adolescence in boys only (all CpG sites with FDR<20%). Sites with greater than 5% differential methylation are highlighted in gray.

Table S5 Correlation between maternal stress during infancy and increased DNA methylation in adolescence in girls only (all CpG sites with FDR <20%). Sites with greater than 5% differential methylation are highlighted in gray.

Table S6 Correlation between paternal stress during infancy and decreased DNA methylation in adolescence in girls only (all CpG sites with FDR<20%). Sites with greater than 5% differential methylation are highlighted in gray.

Table S7 Correlation between paternal stress during preschool and increased DNA methylation in adolescence in girls only (all CpG sites with FDR<20%). Sites with greater than 5% differential methylation are highlighted in gray.

Table S8 Comparison of correlations between paternal stress during preschool and increased DNA methylation in adolescence in full sample and girls only (limited to all CpG sites with FDR<20% from full sample). All sites with FDR<20% in girls only are highlighted in gray.

Table S9 Correlation between paternal stress during preschool and decreased DNA methylation in girls only (all CpG sites with FDR<20%). Sites with greater than 5% differential methylation are highlighted in gray.

Table S10 Genes with DNA methylation of more than 1 CpG site correlated with paternal stress during preschool in girls only (all CpG sites with FDR<20%). Sites with greater than 5% differential methylation are highlighted in gray.

Table S11 DAVID analysis to determine GO term enrichment for genes whose DNA methylation level was correlated with maternal stress during infancy in the full sample. All CpG sites with FDR<20% from Table S2 were used for DAVID analysis.