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), but the biological mechanisms linking psychosocial stress with health disparities 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 (before age 20) produces DNA methylation profiles that contribute to health disparities in obesity-related outcomes and are transmitted across generations, but can be mitigated by protective factors from individual, interpersonal, and community domains. To achieve the goals of this project, we will capitalize on an existing longitudinal study, the Birmingham Youth Violence Study, which collected prospective, multi-informant data on a variety of early life stressors and protective factors in over 500 individuals (78% Black, 22% White, 50% female) in Birmingham, Alabama, longitudinally at average ages 11, 13 and 19. This project will conduct a follow up assessment on 400 young adults from this cohort (average age 26) and 200 of their offspring (ages 0 to 5). It will involve a comprehensive evaluation of obesity and related biomarkers (blood pressure, glycated hemoglobin, inflammation markers) in the young adults; assessment of obesity and history of early life stress in the offspring; and collection and analyses of salivary DNA from both the young adults and their offspring. The combined data will be used to 1) identify DNA methylation variations that are associated with early life stress and obesity in young adulthood; 2) identify multi-level protective factors that attenuate the associations of early life stress with DNA methylation and obesity; and 3) characterize the extent to which stress-related DNA methylation patterns transmit across generations and contribute to offspring obesity. The findings of this study will provide novel insights into stress-related epigenetic mechanisms that may explain racial health disparities and their transmission across generations, as well as multi-level protective factors that may interrupt the perpetuation of biologically embedded adversity across generations. Better understanding of these processes 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.
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