Pronounced disparities exist by race, ethnicity, and SES in children and adolescents across a range of health conditions, and many adult health disparities can be traced to childhood social contextual inequalities. Epigenetics — modifications to the genome that are not changes in nucleotide sequence — holds great promise as potential indicators of contextual effects and health condition, potentially uncovering health disparities long before they are normally observable. Building on an existing representative study of children, this proposal will directly respond to PAR-16-355 by: 1) assembling epigenome-wide data on 2,000 children at two points in time, 2) describing methylation patterns in 3 race/ethnic groups and across SES levels, and 3) explicating epigenetic associations with social adversity, biological processes, and socioemotional development. The overarching hypothesis is that DNA methylation partially mediates the effect of adverse social context (i.e. poverty, harsh parenting, neighborhood disorganization, family instability, and parental incarceration) on biological processes related to stress response (telomere length and attrition, cortisol response, DHEA levels) and stress responsive behaviors (behavioral problems, risk taking, and resilience). We further hypothesize both differential exposure and differential response to adversity by race/ethnicity and SES explains some of the disparity in stress response and socioemotional development — thereby requiring formal comparisons of race/ethnicity and SES in the same study. To conduct this research we utilize the Fragile Families and Child Wellbeing Study (FFCWS): a 20-city nationally and city representative sample of 4898 children born in 1998-2000. FFCW provides a uniquely high prevalence of non-Hispanic Black (47%), Hispanic (27%), and impoverished families, making the data particularly useful for studying race/ethnic and SES differences. Families were interviewed at birth and at ages 1, 3, 5, 9, and 15 — with biological data collected at ages 9 and 15. The expected results will be to provide estimates of: 1) population-based epigenome-wide DNA methylation measures for 3 race/ethnic groups (Hispanic n=600, African ancestry n=980, European ancestry n=420) in childhood and adolescence, 2) associations of social adversity across development (from in utero to age 15) with DNA methylation, 3) associations between DNA methylation and biological measures of stress response (i.e. telomere length and attrition, cortisol response, and DHEA levels), 4) associations between development of stress response behaviors and methylation profiles, and 5) comparisons of all these relationships in 3 race/ethnic groups and across a wide range of SES.