Long-term molecular embedding of early life adversity: leukocyte DNA methylation and gene expression associations from childhood to young adulthood

BACKGROUND: Early life adversity is associated with increased cardiometabolic risk across the life course, potentially via epigenetic mechanisms. However, few studies have prospectively examined how distinct domains of early life adversity influence molecular profiles and cardiometabolic health. RESEARCH DESIGN AND METHODS: In the CHAMACOS cohort, a longitudinal study of rural Latino youth, we measured adversity prospectively from pregnancy through age 7 across six domains: Learning Environment, Parent-Child Interaction, Maternal Adversity, Family Dysfunction, Economic Adversity, and Stressful Life Events. Leukocyte DNA methylation (DNAm) was measured at four timepoints between ages 7 and 18, gene expression (RNA transcripts) at age 14, and body mass index (BMI) and insulin resistance (HOMA-IR) at age 18. RESULTS: Early life adversity was associated with differential DNAm at ages 7, 14, and 18, with 14 Bonferroni- and 101 FDR-significant differentially methylated probes (DMPs) across all timepoints. Economic adversity was the domain most strongly associated with DMPs (4 Bonferroni- and 38 FDR-significant). Methylation changes at several DMPs were significantly associated with BMI and HOMA-IR at age 18. CONCLUSIONS: These findings provide longitudinal evidence that early life adversity, particularly economic adversity, becomes biologically embedded via DNAm, with functional and cardiometabolic consequences, highlighting potential targets for early interventions to reduce lifelong disease risk.