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.

项目概要/摘要 尽管是最富裕的发达国家之一，但孕产妇死亡率仍在上升 美国，在过去三十年里几乎翻了一番。孕产妇死亡率的种族差异也 扩大，黑人孕产妇死亡率是白人的三倍多。研究 探索健康的社会决定因素一直发现产前不充分 照料、贫困和压力是造成不同的不良负担的部分原因 妊娠结局（APO），例如黑人中的先兆子痫。然而， 即使在调整了这种社会经济因素之后，黑人之间的明显种族差异仍然存在 和心理社会因素。为了缩小先兆子痫的这种差异，需要进行额外的研究 充分了解原因至关重要。虽然种族是一种社会建构，但其后果 这种结构可以产生生物学影响。表观基因组学代表了一个领域，其中 可以探索和细致入微地探讨环境和行为因素对基因表达的影响 可以确定病理生理学机制。拟议的分析将使我们能够 利用现有资源来解决有关文献中的关键证据差距 压力、种族和先兆子痫之间的表观遗传关系。 未产儿妊娠结局研究：监测准妈妈 (nuMoM2b) 注册了 期间，美国 8 个学术医疗中心对 10,038 名健康的未产妇进行了多样化队列研究 2010-2013 年，他们从受孕早期到第一个孩子的分娩都受到跟踪。 对于妊娠特征和妊娠，存在大量的临床表型数据 这些研究参与者的结果。 nuMoM2b 心脏健康研究由 7,003 名患者组成 nuMoM2b 出生后至少重新联系过一次的 nuMoM2b 参与者，其中 4,508 人 2-7 年后，他们返回进行面对面的心血管危险因素评估。第三个 亲自访问的研究浪潮将于 2022 年初开始。因此，该群体具有独特的优势 解决有关压力在先兆子痫病理生理学中的作用的问题。有了这个 行政补充，我们将利用现有样本和数据来（1）确定因素 与黑人相比，这会导致黑人患先兆子痫的风险更大 白人，(2) 产生一个大型甲基化数据集，这将在现有的基础上添加另一层 数据（GWAS、蛋白质组学），产生了全球最大的怀孕个体多组学数据集 美国，（3）可以用于未来的纵向分析，以检查压力如何， 自我认同的种族、其他行为因素和先兆子痫导致了 怀孕后数年的心血管疾病。