Prenatal Multi-Level Stressors and Alterations in Maternal and Fetal Epigenomes

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 DESCRIPTION (provided by applicant): Growing evidence indicates that maternal psychosocial stressors during pregnancy, e.g. depression, anxiety, and stressful life events are related to poor birth outcomes. However, the epigenetic mechanisms underlying associations between maternal stress and child health outcomes remain largely unexplored. We propose a trans-disciplinary study to test the hypothesis that maternal psychosocial stressors can affect both maternal and newborn DNA methylation profiles, detectable at the time of delivery. Specifically, we propose to investigate 1) maternal emotional disorders, including major depression and anxiety disorders and 2) maternal psychosocial stressors (e.g. stressful life events, witnessing violence, poor social support), in relation to altered maternal and newborn DNA methylation patterns. In addition, we will 3) compare similarities and differences in the methylation signatures of mothers and their newborns. A unique feature of this proposal is that we will examine responses to emotional and psychosocial stressors in DNA methylation in mother-infant pairs using both genome-wide and candidate gene approaches, and will evaluate how maternal-child dyads coordinate in coping with stress. Another innovation is that we will examine a broad spectrum of maternal psychological stressors. Successful completion of this proposed study will establish a foundation for a prospective study on epigenetic changes at birth and during the postnatal period, and their link with a range of child health and developmental outcomes. A particular strength of this proposal is that we will leverage the existing resources of the Boston Birth Cohort (BBC), an ongoing large longitudinal, predominantly urban African-American birth cohort (now consisting of ~8500 mother-infant pairs). This study will leverage extensive high-quality epidemiological and clinical data, along with biospecimens already obtained by the BBC. The BBC is well-suited for addressing the study hypotheses due to a high prevalence of maternal psychosocial stressors during pregnancy, high rates of pregnancy complications and adverse pregnancy outcomes. We have already measured genome-wide DNA methylation in 400 mothers and 400 babies from the BBC and demonstrated promising associations between maternal stressors and DNA methylation both at the genome-wide scale and in specific candidate genes. We expect that this proposed study will identify DNA methylation signatures of maternal psychosocial stressors and will lay a foundation to further investigate the long-term health consequences of maternal stress-induced DNA methylation changes in both the mother and her child.