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

• 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
• 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

 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（由申请人提供）：越来越多的证据表明，怀孕期间母亲的社会心理压力源，例如抑郁、焦虑和压力性生活事件与不良的出生结果有关。然而，孕产妇压力与儿童健康结果之间关联的表观遗传机制在很大程度上仍未得到探索。我们提出了一项跨学科研究来检验以下假设：母亲心理社会压力因素会影响母亲和新生儿 DNA 甲基化谱（在分娩时可检测到）。具体来说，我们建议调查 1) 孕产妇情绪障碍，包括重度抑郁症和焦虑症，以及 2) 孕产妇社会心理压力源（例如压力性生活事件、目睹暴力、不良社会支持）与孕产妇和新生儿 DNA 甲基化模式改变的关系。此外，我们将 3) 比较母亲及其新生儿甲基化特征的异同。该提案的一个独特之处在于，我们将使用全基因组和候选基因方法来检查母婴对 DNA 甲基化对情感和社会心理压力源的反应，并将评估母婴二人在应对压力时如何协调。另一项创新是我们将研究广泛的母亲心理压力源。这项拟议研究的成功完成将为出生时和产后期间的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。该提案的一个特别优势是我们将利用现有资源 波士顿出生队列 (BBC)，一个持续进行的大型纵向、主要是城市非裔美国人出生队列（现在由约 8500 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，以及 BBC 已经获得的生物样本。由于怀孕期间母亲心理社会压力源的发生率很高、妊娠并发症和不良妊娠结局的发生率很高，BBC 非常适合解决该研究假设。我们已经测量了 BBC 的 400 名母亲和 400 名婴儿的全基因组 DNA 甲基化，并在全基因组规模和特定候选基因中证明了母体压力源与 DNA 甲基化之间的良好关联。我们期望这项拟议的研究将确定母亲心理社会压力源的 DNA 甲基化特征，并为进一步研究母亲压力引起的母亲和孩子的 DNA 甲基化变化的长期健康后果奠定基础。