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 尽管是最富有的发展国家之一，但孕产妇死亡率正在上升 美国，在过去的三十年中几乎翻了一番。孕产妇死亡率的种族差异也 加宽，黑人死亡率超过三倍，是白人个体的三倍以上。研究 探索健康的社会决定因素一直确定产前不足 护理，贫穷和压力是部分负担不利负担的领域 妊娠结局（APO），例如黑人个体中的先兆子痫。但是， 即使调整了这样的社会经济，黑人的种族差异仍然存在 和社会心理因素。为了缩小先兆子痫的差异，其他研究 充分理解原因至关重要。虽然种族是一种社会结构，但 该结构可以产生生物学影响。表观基因组学代表了一个领域 可以探索和细微探索基因表达的环境和行为因素 可以鉴定出病理生理的机制。提出的分析将使我们能够 利用现有资源来解决文献中有关的关键证据差距 压力，种族和子痫前期的表观遗传关系。 无效的怀孕结果研究：监测准母亲（NUMOM2B） 在美国8个学术医疗中心的10,038名健康无性妇女组成的多元化队列 2010 - 2013年，从孕育早期开始通过第一个孩子就受到关注。 对于怀孕特征和怀孕而存在广泛的临床表型数据 这些研究参与者的结果。 NUMOM2B心脏健康研究由7,003 NUMOM2B参与者在NUMOM2B出生后至少重新连接一次，4,508个 2 - 7年后，他返回接受亲自的心血管危险因素评估。第三 面对面访问的研究浪潮将于2022年初开始。因此，该队列的位置唯一地定位于 解决有关压力在先兆子痫病理生理学中的作用的问题。与此 行政补充，我们将资本将现有样本和数据大写为（1）确定因素 与 白人，（2）产生一个大的甲基化数据集，将为现有 数据（GWAS，蛋白质组学），导致最大的多词数据集的孕妇 美国，可以利用（3）来进行未来的纵向分析，以研究压力， 自我认同的种族，其他行为因素和子痫前期有助于出现 怀孕后几年的心血管疾病。