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

产前多级应激源和母亲和胎儿表观基因组的改变

基本信息

批准号：
9111244
负责人：
PAMELA J SURKAN
金额：
$ 24.45万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9111244
关键词：
Address Affect African American Anxiety Anxiety Disorders Biological Birth Blood specimen Boston Candidate Disease Gene Child Child Mental Health Child health care Clinical Data DNA Methylation Data Development Emotional Emotional disorder Epidemiology Epigenetic Process Event Fetus Foundations Funding Future Generations Genetic Predisposition to Disease Health High Prevalence Individual Infant Investigation Knowledge Lead Life Link Literature Major Depressive Disorder Measures Mental Depression Methylation Mothers National Institute of Child Health and Human Development Newborn Infant Outcome Pathway interactions Population Pregnancy Pregnancy Complications Prospective Studies Public Policy Reporting Resources Sampling Social support Stress Testing Time Umbilical Cord Blood Violence adverse pregnancy outcome biological adaptation to stress cohort coping cost efficient environmental stressor epigenome experience fetal genome-wide genome-wide analysis innovation insight maternal stress methylation pattern novel offspring postnatal prenatal psychological stressor psychosocial public health intervention public health relevance resilience response stressor success

项目摘要

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.

描述（由适用提供）：越来越多的证据表明，怀孕期间的母质心理压力源，例如抑郁，焦虑和压力大的生活事件与出生不良有关。然而，母子压力与儿童健康结果之间存在的表观遗传机制在很大程度上仍然是出乎意料的。我们提出了一项跨学科研究，以检验以下假设，即母亲心理压力源会影响母体和新生的DNA甲基化谱，可在分娩时检测到。具体而言，我们建议研究1）与遗产和新生儿DNA甲基化模式有关的孕产妇情绪障碍，包括严重的抑郁症和焦虑症以及2）孕产妇的社会心理压力源（例如，压力大的生活事件，见证暴力，社会支持不佳）。此外，我们将3）比较母亲及其新生儿的甲基化特征的相似性和差异。该提案的一个独特特征是，我们将使用全基因组和候选基因方法的母亲对中DNA甲基化中对情绪和心理社会压力源的反应，并将评估母婴二元组如何应对压力。另一个创新是，我们将研究各种各样的母体心理压力源。这项拟议的研究的成功完成将为出生时和产后表观遗传变化的前瞻性研究奠定基础，以及它们与一系列儿童健康和发展结果的联系。该提案的一个特殊优势是，我们将利用波士顿出生队列（BBC）是一个正在进行的大型纵向，主要是城市非裔美国人出生队列（现在由约8500个母亲成对组成）。这项研究将利用广泛的高质量流行病学和临床数据，以及BBC已经获得的生物测量。英国广播公司非常适合解决研究假设，因为怀孕期间母亲的社会心理压力源高，怀孕并发症发生率高和不良怀孕结果。我们已经在BBC中测量了400名母亲和400名婴儿的全基因组DNA甲基化，并且在基因组范围和特定候选基因中都表现出了母子胁迫与DNA甲基化之间的有希望的关联。我们预计这项拟议的研究将确定孕产妇的社会心理压力源的DNA甲基化特征，并将为进一步研究母亲胁迫诱导的母亲和孩子的DNA甲基化变化带来的长期健康后果。