Early life trauma patterns and adult epigenome-wide and NR3C1-specific DNA methylation in the Sister Study

Patterns of co-occurring early life trauma (ELT), unlike cumulative trauma, are understudied as potential stress-related health risks. DNA methylation (DNAm) is a posited mechanism linking socioenvironmental stress and disease pathogenesis. We assess whether ELT patterns differentially affect adult DNAm, both epigenome-wide and specifically stress-related genes (eg, glucocorticoid receptor gene, NR3C1). Data represent a case-cohort of non-Hispanic white participants (N = 2566) from the Sister Study, a cohort of US women (ages: 35-74; enrollment: 2003-2009; N = 50 884). Early life trauma measures included a count score and 4 latent ELT classes: low ELT (referent); sexual and emotional; high betrayal; and high ELT. We evaluated epigenome-wide DNAm, differentially methylated regions (DMRs), pathway enrichment, and NR3C1-specific methylation from whole blood. Twenty-two differentially methylated Cytosine-phosphate-Guanine (CpG) sites were associated with ELT classes and none with ELT score. Furthermore, 108 DMRs were associated with ELT score (n = 5) and ELT classes: sexual and emotional (n = 7), high betrayal (n = 37), and high ELT (n = 61). Cardiovascular signaling and leptin signaling pathways were both associated with high betrayal and high ELT classes. In NR3C1-specific analyses, 11 CpGs were associated with ELT score (n = 3) and specific ELT classes (n = 9). Results suggest that specific patterns of co-occurring trauma may contribute to meaningful variability in peripheral blood DNAm in adulthood.