**Background:** Children's cognitive functioning and educational performance are socially stratified by socioeconomic status and race/ethnicity. Epigenetic mechanisms, particularly DNA methylation, are hypothesized to mediate the biological embedding of environmental privilege and disadvantage. This study examined whether salivary DNA methylation profiles originally developed in adults—reflecting inflammation (DNAm-CRP), cognitive performance (Epigenetic-g), and pace of biological aging (DunedinPoAm)—are (a) stratified by social inequality and (b) associated with cognitive function in children and adolescents.
**Methods:** Participants were 1,183 children and adolescents (609 female, ages 8–19 years, M=13.6, SD=3.05) from the population-based Texas Twin Project, including 426 monozygotic and 757 dizygotic twins from 611 families. Saliva samples were collected using Oragene kits and methylation was assessed using the Infinium MethylationEPIC BeadChip (850,000 sites). Three DNA methylation composite scores were computed: DNAm-CRP (based on 218 CpG sites from an EWAS of C-reactive protein), Epigenetic-g (based on an EWAS of general cognitive function in adults), and DunedinPoAm (a 46-CpG algorithm measuring pace of aging). Cognitive function was assessed using a battery of tasks measuring processing speed (Symbol Search, Pattern Comparison, Letter Comparison), executive functions (15 tasks across inhibition, switching, working memory, updating), perceptual reasoning and verbal comprehension (Wechsler Abbreviated Scale of Intelligence), and reading and math (Woodcock-Johnson III). Socioeconomic context was measured at the family level (composite of income, education, occupation, financial problems, food insecurity, father absence, residential instability, public assistance) and neighborhood level (tract-level Census data on unemployment, poverty, education, occupation, single mothers, and intergenerational economic mobility from the Opportunity Atlas). Multilevel multivariate regression models with cluster-robust standard errors were used, controlling for age, gender, and age-by-gender interaction. Multiple testing was controlled using the Benjamini-Hochberg false-discovery-rate method.
**Key Results:** DNA methylation profiles showed moderate-to-good reliability (ICC: DNAm-CRP=.73, Epigenetic-g=.80, DunedinPoAm=.84). Higher DNAm-CRP was strongly correlated with faster DunedinPoAm (r=.89, 95% CI [.81, .96], p<.001) and moderately correlated with lower Epigenetic-g (r=-.31, 95% CI [-.42, -.19], p<.001). Children from socioeconomically disadvantaged families and neighborhoods exhibited DNA methylation profiles associated with higher inflammation, faster aging, and lower cognitive function. Children identifying as Latinx-only or Black+ showed higher DNAm-CRP, faster DunedinPoAm, and lower Epigenetic-g compared to White-only children. Family-level socioeconomic disadvantage accounted for racial/ethnic disparities in DNAm-CRP but not Epigenetic-g; it accounted for DunedinPoAm differences between Black+ and White-only but not Latinx-only and White-only children. White identity remained associated with more favorable Epigenetic-g (r=.21, 95% CI [.13, .29], p<.001) and DunedinPoAm (r=-.19, 95% CI [-.29, -.09], p<.001) after accounting for family-level disadvantage. Higher DNAm-CRP was associated with worse processing speed (r=-.15, p=.003), executive function (r=-.21, p=.004), perceptual reasoning (r=-.16, p=.001), and verbal comprehension (r=-.14, p=.013). Lower Epigenetic-g was associated with lower perceptual reasoning (r=.15, p<.001), verbal comprehension (r=.17, p=.001), reading (r=.22, p=.001), and math (r=.33, p<.001), with Epigenetic-g explaining 11.1% of variance in math performance. Faster DunedinPoAm was associated with lower perceptual reasoning (r=-.20, p<.001) and verbal comprehension (r=-.19, p<.001). Associations of DNAm-CRP and DunedinPoAm with cognition were largely accounted for by family-level disadvantage, while Epigenetic-g associations were unaffected. Within-family (cotwin control) analyses showed no evidence that twins differing in DNA methylation differed in cognitive function, suggesting associations arise at the between-family level.
**Clinical Implications:** These findings demonstrate that social inequalities in childhood are reflected in molecular epigenetic signatures that, in adults, are linked to chronic inflammation, accelerated aging, and reduced cognitive function. Salivary DNA methylation profiles may serve as useful biomarkers for indexing social inequality and risk for cognitive disparities in childhood. The results support the hypothesis that adult health and cognitive disparities are partially driven by molecular processes originating in childhood, a sensitive developmental period. However, the cross-sectional design precludes causal inference, and the tissue specificity of DNA methylation (saliva vs. blood) warrants caution. The findings highlight the potential for using salivary epigenetic measures in large-scale pediatric studies to evaluate interventions addressing childhood social determinants of lifelong health and cognitive outcomes.