This application is a response to PAR #16-355 “Social Epigenomics Research Focused on Minority Health and Health Disparities.” In the contemporary United States, children’s outcomes vary substantially by their family’s socioeconomic status (SES). These disparities are present in multiple domains, including cognitive development, psychiatric disorders, and physical health. As low-SES youth mature into adulthood, they continue to have disproportionately poor outcomes, as reflected in poverty rates, mental health problems, and morbidity and mortality from chronic diseases associated with aging. Social science has identified a variety of structural, contextual, and psychological factors that contribute to these disparities. But we have only a superficial understanding of how these factors “get under the skin” to influence biological processes that are proximally involved in brain maturation, health problems, and other outcomes that pattern by SES. Recently, theorists have addressed this question by posting that socioeconomic disadvantage gets biologically embedded during gestation, a sensitive period when multiple organ systems are developing. Animal models show that gestational influences of this sort are possible, and mediated in significant part through modulation of epigenetic and transcriptional processes in the placenta. Nevertheless, studies have yet to comprehensively examine the plausibility of the embedding hypothesis in human subjects. We seek to fill this gap here by recruiting an economically diverse sample of 700 women during pregnancy, and characterizing multiple dimensions of their lifecourse socioeconomic conditions. At delivery, we will biopsy women’s placentas, and measure gene regulation in a biologically integrated fashion by assaying patterns of DNA methylation (DNAm), and expression of microRNA (miRNA) and messenger RNA (mRNA). We hypothesize that to the extent that women are lower in SES, their placental biopsies will show epigenetic and transcriptional patterns indicative of lower fetal tolerance, greater immune activation, and slower organ maturation. Using data from geocoding, interviews, and questionnaires, we also will develop a multilevel framework. It will specify connections between features of neighborhoods (economic deprivation, violent crime, residential segregation, social capital), families (job instability, financial duress, relationship qualities), and individuals (depressive symptoms, pregnancy anxiety, lifestyle factors), and characterize the strength and nature of their associations with dimensions of placental gene regulation, i.e., DNAm, miRNA, and mRNA. Finally, we will clarify the clinical implications of these patterns by examining their connections to preterm birth and growth restriction. We hypothesize that lower SES women will experience higher incidences of both conditions relative to higher SES women. Using mediation analyses, we will attempt to identify molecular pathways that contribute to these disparities, with an emphasis on chronic inflammatory lesions in the placenta, and epigenetic and transcriptional modifications that initiate and/or maintain them.
|Effective start/end date||9/26/17 → 5/31/22|
- National Institute on Minority Health and Health Disparities (5R01MD011749-04 REVISED)