Epigenome-wide Association Study of Preterm Birth

早产的全表观基因组关联研究

基本信息

批准号：
7991305
负责人：
XIAOBIN WANG
金额：
$ 24.9万
依托单位：
LURIE CHILDREN'S HOSPITAL OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7991305
关键词：
Address Affect African American Arts Biological Birth Birth Weight Blood Blood specimen Boston Candidate Disease Gene Cells Child Collaborations Collection Coupled DNA Methylation DNA analysis Data Databases Development Disease Embryo Environment Environmental Exposure Environmental Risk Factor Epidemiology Epigenetic Process Etiology Exposure to Funding Future Gametogenesis Gene Expression Regulation Generations Genes Genetic Genetic Predisposition to Disease Genetic Transcription Genomics Genotype Health High Prevalence Human Incidence Individual Infant Interdisciplinary Study Knowledge Literature Live Birth Longevity Maps Maternal Age Minority Morbidity - disease rate Mothers Neonatal Pathway interactions Phenotype Pilot Projects Play Population Pregnancy Premature Birth Premature Infant Prevention Productivity Publishing Race Regulation Research Risk Role Staging Statistical Methods Stimulus Testing Tissues Umbilical Cord Blood Venous blood sampling Weight maintenance regimen Work base cohort cost design epigenomics experience fetal genetic variant genome wide association study genome-wide high risk inner city innovation insight mortality novel strategies nuclear reprogramming parity prevent public health relevance repository trait

项目摘要

DESCRIPTION (provided by applicant): Preterm Birth (PTB), commonly defined as delivery of an infant before 37 weeks of gestation, affects 12.6% of all births in the U.S. A major obstacle in preventing and treating PTB has been our incomplete understanding of its etiology and biological mechanisms. Both the literature and our work have provided compelling evidence that PTB is influenced by environmental and genetic factors and their interactions. To date, PTB research has largely omitted epigenomics, which unites mechanisms of nuclear reprogramming during development with environmentally induced biological changes, and the ability of cells to respond to external stimuli. The central focus of this proposal is to identify epigenomic alterations in the context of individual genetic susceptibility and environmental exposures and to gain important insight into the biological mechanisms by which genomic, epigenomic, and environmental factors affect the risk of PTB. We propose to accomplish the following aims. Aim 1: We will conduct epigenomic mapping among 500 African American mothers, including 250 spontaneous very preterm cases and 250 term, normal birth weight controls drawn from the existent Boston Birth Cohort. We will use the Illumina HumanMethylation27 DNA Analysis BeadChip for epigenomic mapping. We will test the hypothesis that alterations of DNA methylation in maternal venous blood samples obtained at birth are associated with the risk of PTB. Aim 2: We will conduct epigenomic mapping among 500 infants born to the mothers included in Aim 1, using the same Illumina platform. We will test the hypothesis that alterations of DNA methylation in cord blood samples obtained at birth are associated with the risk of PTB. Exploratory Analysis: We will utilize the extensive database of the Boston Birth Cohort to simultaneously evaluate the roles of environment, genomic, and epigenomic factors as well as their interactions in PTB. We will also explore the interplay of maternal and fetal epigenome in relation to PTB. This will be the first epigenomic study of PTB in conjunction with GWAS in African American mother-infant pairs, a population with high prevalence of socio-environmental adversities and high risk of PTB. This proposal has many unique features, including a highly cost-efficient study by using an existent well-designed and well-phenotyped birth cohort; an innovative approach to integrate environment, genomic and epigenomic factors in PTB; and a highly interactive and experienced multidisciplinary research team with a track record of collaboration and productivity. This proposed study has a great potential to transform our understanding of the etiology and biological mechanisms of PTB, especially, among high risk inner-city minority populations, which will be of key importance for lowering the incidence of PTB and reducing preterm disparity in the U.S. PUBLIC HEALTH RELEVANCE: In the U.S, more than one out of every eight live births is premature infants (PTB) each year. PTB is a major cause of infant morbidity and mortality and is associated with increased risk for a wide range of short- and long-term health and developmental problems. The central focus of this proposal is to identify maternal and fetal epigenomic alterations in relation to PTB. Findings from this study will help gain important insight into how genomic, epigenomic, and environmental factors affect the risk of PTB.

描述（由申请人提供）：早产（PTB）通常定义为妊娠37周之前的婴儿的递送，影响了美国所有出生的12.6％，这是我们预防和治疗PTB的主要障碍，这是我们对其病因和生物学机制的不完全理解。文献和我们的工作都提供了令人信服的证据，表明PTB受环境和遗传因素及其相互作用的影响。迄今为止，PTB的研究在很大程度上省略了表观基因组学，这将在发育过程中的核重编程机制与环境诱导的生物学变化以及细胞对外部刺激做出反应的能力结合在一起。该提案的主要重点是在个体遗传易感性和环境暴露的背景下确定表观基因组改变，并获得对基因组，表观基因组和环境因素影响PTB风险的生物学机制的重要见解。我们建议实现以下目标。 AIM 1：我们将在500名非裔美国母亲中进行表观基因组映射，其中包括250个自发的早产案和250个学期，这是从现有的波士顿出生队列中得出的正常出生体重控制。我们将使用Illumina Human -Methylation27 DNA分析Beadchip进行表观基因组映射。我们将测试以下假设：在出生时获得的母体静脉血液样本中DNA甲基化的改变与PTB的风险有关。 AIM 2：我们将使用相同的Illumina平台对AIM 1中的母亲出生的500名婴儿进行表观基因组图。我们将检验以下假设：在出生时获得的脐带血样品中DNA甲基化的改变与PTB的风险有关。探索性分析：我们将利用波士顿出生队列的广泛数据库同时评估环境，基因组和表观基因组因子的作用以及它们在PTB中的相互作用。我们还将探讨与PTB相关的母体和胎儿表观基因组的相互作用。这将是PTB与GWAS在非洲裔美国母亲成对中的首次表观基因组学研究，这是社会 - 环境逆境较高的人群，PTB的高风险。该提案具有许多独特的功能，包括使用现有的精心设计且良好的型出生队列的研究；一种创新的方法来整合PTB中的环境，基因组和表观基因组因子；以及一个高度互动且经验丰富的多学科研究团队，具有协作和生产力的记录。这项拟议的研究具有改变我们对PTB的病因和生物学机制的理解，特别是在高风险内城市少数族裔人口中，这对于降低PTB的发生和降低美国的早产差异至关重要，这将是至关重要的。公共卫生相关性：在美国，每八个活产中有一个以上是早产儿（PTB）。 PTB是婴儿发病率和死亡率的主要原因，与长期和长期健康和发育问题的风险增加有关。该提案的主要重点是确定与PTB有关的孕产妇和胎儿表观基因组的改变。这项研究的发现将有助于对基因组，表观基因组和环境因素如何影响PTB的风险有重要了解。