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

 描述（由申请人提供）：越来越多的证据表明，母亲在怀孕期间的心理社会压力，如抑郁，焦虑和压力性生活事件与不良的出生结果有关。然而，产妇压力和儿童健康结果之间的联系的表观遗传机制仍然在很大程度上未被探索。我们提出了一个跨学科的研究来检验这一假设，即产妇的心理社会压力可以影响产妇和新生儿的DNA甲基化谱，在分娩时检测。具体而言，我们建议调查1）产妇情绪障碍，包括重度抑郁症和焦虑症，2）产妇心理社会压力（例如压力性生活事件，目睹暴力，社会支持不足），与母亲和新生儿DNA甲基化模式的改变有关。此外，我们将3）比较母亲和新生儿甲基化特征的相似性和差异。这项提案的一个独特之处是，我们将使用全基因组和候选基因方法研究母婴对DNA甲基化对情感和心理压力的反应，并评估母婴二人组如何协调应对压力。另一个创新是，我们将研究广泛的产妇心理压力。这项拟议研究的成功完成将为出生时和产后时期表观遗传变化及其与一系列儿童健康和发育结果的联系的前瞻性研究奠定基础。这项建议的一个特别优点是，我们将利用现有的资源， 波士顿出生队列（BBC），一个正在进行的大型纵向，主要是城市非洲裔美国人出生队列（现在由约8500对母婴组成）。这项研究将利用广泛的高质量流行病学和临床数据，沿着英国广播公司已经获得的生物标本。英国广播公司是非常适合解决的研究假设，由于在怀孕期间，产妇的心理社会压力，怀孕并发症和不良妊娠结局的高发病率。我们已经测量了来自BBC的400名母亲和400名婴儿的全基因组DNA甲基化，并在全基因组范围和特定候选基因中证明了母体压力源和DNA甲基化之间的潜在关联。我们期望这项拟议的研究将确定母亲心理社会压力的DNA甲基化特征，并为进一步研究母亲和她的孩子的母亲压力诱导的DNA甲基化变化的长期健康后果奠定基础。

 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.