Early Life Stress, DNA Methylation, and Health Disparities across Ages

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PROJECT SUMMARY Compared to Whites, Blacks carry a disproportionate burden of chronic disease and early mortality. These health disparities have been linked with high levels of psychosocial stress experienced by Blacks (e.g., poverty, interpersonal violence, and discrimination), but the biological mechanisms linking psychosocial stress with health disparities across the lifespan remain poorly understood. Similarly, the extent to which multi-level protective factors (e.g., from individual, interpersonal, and community domains) mitigate the effects of early life stress on health outcomes and underlying biological mechanisms is unknown. This proposal will investigate the hypothesis that early life stress produces DNA methylation profiles that contribute to health disparities in early markers of chronic disease across several age groups, and these effects are modified by protective factors from individual, interpersonal, and community domains. To achieve the goals of this project, we will capitalize on an existing longitudinal study, Healthy Passages, which collected prospective, multi-informant data on a variety of early life stressors and protective factors in over 1,000 individuals (65% Black, 35% White, 50% female) in Birmingham, Alabama at ages 11, 13, 16, and 19. The proposed project will conduct a follow up assessment on 800 young adults from this cohort (average age 28) and 400 of their offspring (ages 0 to 5). It will involve a comprehensive evaluation of cardiometabolic indicators associated with later chronic disease (obesity, hypertension, hyperglycemia, and inflammation) in the young adults; assessment of prenatal and postnatal stress and protective factors in the offspring; and analyses of saliva DNA from the young adults at ages 19 and 28, and their offspring. The combination of existing and newly collected data will be used to 1) identify DNA methylation variations that are associated with early life stress and cardiometabolic indicators across three developmental periods – early childhood, late adolescence, and young adulthood; 2) examine the role of race in stress-related DNA methylation and cardiometabolic indicators across the three developmental periods; and 3) identify multi-level protective factors that modify the effects of early life stress on DNA methylation across the three developmental periods. The findings of this study will provide novel insights into stress-related epigenetic mechanisms that may explain racial health disparities across the lifespan, as well as multi-level protective factors that may interrupt the biological embedding of adversity. Better understanding of the role of epigenetics in health disparities may lead to development of epigenetic biomarkers for early diagnosis of disease, ability to identify susceptible individuals at risk for adult disease, and development of novel preventive and curative measures that would reduce health disparities.