Stress and Racial Disparities in Preeclampsia - Clues from DNA Methylomic Profiling

先兆子痫的压力和种族差异 - DNA 甲基组学分析的线索

• 批准号: 10418273
• 负责人: Philip Greenland
• 金额: $ 21.97万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10418273
• 关键词: Academic Medical Centers; Address; Administrative Supplement; Area; Behavioral; Biological; Birth; Cardiac health; Cardiovascular Diseases; Characteristics; Child; Cohort Studies; Conceptions; DNA; Data; Data Set; Developed Countries; Development; Enrollment; Environmental Impact; Epigenetic Process; Functional disorder; Future; Gene Expression; Gestational Diabetes; Individual; Literature; Maternal Mortality; Methylation; Monitor; Mothers; Multiomic Data; Nulliparity; Outcome Study; Participant; Persons; Positioning Attribute; Poverty; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Prenatal care; Proteomics; Psychosocial Factor; Race; Research; Resources; Risk; Role; Sampling; Small for Gestational Age Infant; Socioeconomic Factors; Stress; Time; Visit; Woman; Work; adverse pregnancy outcome; cardiovascular risk factor; clinical phenotype; cohort; epigenomics; genome wide association study; longitudinal analysis; methylomics; pathophysiology of preeclampsia; phenotypic data; pregnancy disorder; pregnant; racial disparity; social; social health determinants

Project Summary/Abstract Despite being one of the wealthiest developed nations, maternal mortality is on the rise in the U.S., almost doubling in the last thirty years. Racial disparities in maternal mortality have also widened, with Black maternal mortality more than three times that for White individuals. Studies exploring the social determinants of health have consistently identified inadequate prenatal care, poverty, and stress as areas partially responsible for the disparate burden of adverse pregnancy outcomes (APOs) such as preeclampsia among Black individuals. However, the stark racial disparity for Black individuals remains, even after adjusting for such socioeconomic and psychosocial factors. In order to narrow this disparity in preeclampsia, additional research to fully understand the cause is crucial. While race is a social construct, the consequences of this construct can have biological impact. Epigenomics represents a field where the impact of environmental and behavioral factors on gene expression can be explored and nuanced mechanisms of pathophysiology can be identified. The proposed analysis will allow us to leverage existing resources to address a key evidence gap in the literature regarding the epigenetic relationship between stress, race, and preeclampsia. The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (nuMoM2b) enrolled a diverse cohort of 10,038 healthy nulliparous women at 8 US academic medical centers during 2010-2013, who were followed from early in conception through the delivery of their first child. Extensive clinical phenotyping data exist for the pregnancy characteristics and pregnancy outcomes of these study participants. The nuMoM2b Heart Health Study is comprised of 7,003 nuMoM2b participants who were recontacted at least once after their nuMoM2b birth, 4,508 of whom returned for an in-person cardiovascular risk factor assessment 2-7 years later. A third study wave of in-person visits will begin in early 2022. This cohort is thus uniquely positioned to address questions about the role of stress in the pathophysiology of preeclampsia. With this administrative supplement, we will capitalize on existing samples and data to (1) identify factors that contribute to greater risk for development of preeclampsia in Black individuals compared to White individuals, (2) produce a large methylation data set that will add another layer to existing data (GWAS, proteomics), resulting in the largest multi-omics data set of pregnant individuals in the U.S., that (3) can be leveraged for future longitudinal analyses that examine how stress, self-identified race, other behavioral factors, and preeclampsia contribute to the emergence of cardiovascular disease in years following pregnancy.

项目摘要/摘要 尽管是最富有的发达国家之一，但孕产妇死亡率在 美国，在过去的30年里几乎翻了一番。孕产妇死亡率的种族差异也 黑人产妇死亡率是白人的三倍多。研究 在对健康的社会决定因素的探索中，一直发现产前不足 护理、贫困和压力是造成不利影响的不同负担的部分原因 妊娠结局(APO)，如黑人中的先兆子痫。然而， 黑人个人的明显种族差距仍然存在，即使在对这样的社会经济进行调整之后也是如此 以及心理社会因素。为了缩小先兆子痫的这种差异，额外的研究 充分了解原因是至关重要的。虽然种族是一种社会结构，但 这种结构可能会产生生物影响。表观基因组学代表了一个领域， 环境和行为因素对基因表达的影响可以被探索和细致入微 其病理生理学机制是可以确定的。拟议的分析将使我们能够 利用现有资源解决文献中有关 应激、种族和先兆子痫之间的表观遗传学关系。 未分娩妊娠结局研究：监测准妈妈(NuMoM2B)招募了一名 美国8个学术医学中心的10,038名健康未分娩妇女的不同队列 2010-2013年，从受孕初期到第一个孩子的分娩都得到了跟踪。 关于妊娠特征和妊娠的临床表型数据广泛存在。 这些研究参与者的结果。NuMoM2B心脏健康研究由7003人组成 NuMoM2B参与者在nuMoM2B出生后至少再次联系过一次，共4,508人 他们在2-7年后回来进行了亲自的心血管危险因素评估。三分之一 面对面访问的学习浪潮将于2022年初开始。因此，这一群体的定位是独特的 回答有关应激在子痫前期的病理生理学中的作用的问题。有了这个 行政补充，我们将利用现有的样本和数据来(1)确定因素 与黑人相比，这会增加黑人患先兆子痫的风险 白人个体，(2)产生一个庞大的甲基化数据集，这将在现有的基础上增加另一层 数据(Gwas，蛋白质组学)，产生了#年最大的怀孕个体多组学数据集 美国认为，(3)可用于未来的纵向分析，以检查压力、 自我认同的种族、其他行为因素和先兆子痫导致了 怀孕数年后的心血管疾病。