Epigenomic Pathways from Racism to Preterm Birth

从种族主义到早产的表观基因组途径

• 批准号: 10561132
• 负责人: Veronica Barcelona
• 金额: $ 54.24万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-14 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10561132
• 关键词: 37 weeks gestation; Address; Affect; Behavioral; Biological; Birth; Black race; Blood; Blood specimen; Candidate Disease Gene; Climate; DNA; DNA Methylation; Data; Discrimination; Ensure; Epigenetic Process; Equity; Ethnic Population; Exposure to; Future; Gene Expression; Genes; Genomic Segment; Geographic Locations; Goals; Health; Health Policy; High Risk Woman; Hispanic; Home; Immigrant; Income; Individual; Infant; Intervention; Knowledge; Longitudinal Studies; Longitudinal cohort study; Maps; Maternal Health; Measures; Mediating; Methylation; Modeling; Mothers; Not Hispanic or Latino; Nulliparity; Outcome; Ownership; Participant; Pathway interactions; Perinatal; Perinatal mortality demographics; Persons; Phenotype; Policy Developments; Politics; Pregnancy; Pregnancy Complications; Pregnant Women; Premature Birth; Prevention; Race; Research; Risk; Risk Factors; Services; Site; Societies; Strategic Planning; Stress; Structural Racism; Subgroup; Tissues; United States; United States National Institutes of Health; Woman; adverse birth outcomes; adverse outcome; black women; cohort; comparison group; early pregnancy; epigenome; epigenome-wide association studies; epigenomics; ethnic disparity; experience; health inequalities; improved; long-term sequelae; maternal stress; methylation biomarker; methylome; molecular marker; multidisciplinary; multiple omics; novel; perceived discrimination; perinatal health; perinatal morbidity; population health; prenatal; prenatal exposure; prospective; racial disparity; racial population; racism; residential segregation; social determinants; stressor; women of color

Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality, with long-term sequelae for both mother and infant. Despite many known risk factors for PTB, prevention and treatment options are limited. Non-Hispanic (NH) Black women are 2-3 times more likely to experience PTB compared to NH White women, and some subgroups of Hispanic women also have increased risk. Racism has been hypothesized as a root cause of perinatal health inequities in the United States (U.S.), yet its mechanisms remain understudied. Epigenetics is a field with great promise for understanding how racism affects gene expression and identifying risk for adverse birth outcomes among women of color. Most studies of epigenomics in pregnancy have had low representation of NH Black and Hispanic women, and few have included structural racism exposures. Further, prospective analyses from early pregnancy to birth outcomes are lacking, limiting identification of high- risk women for improved prenatal surveillance. We propose to address these crucial knowledge gaps by leveraging one of the largest and best-phenotyped cohorts to date, the nuMoM2b Study (2010-2015), a multicenter, longitudinal cohort study of nulliparous pregnant women across the U.S. Existing data from this study include: extracted maternal DNA from blood, Krieger’s individual experiences of discrimination, geocoded participant addresses, pregnancy complications, and birth outcomes. We have assembled a multidisciplinary team with expertise in maternal stress, epigenomics, and perinatal health inequities to complete three aims. Aim 1: Determine the interactive effects of individual- and structural- level racism on PTB among NH Black, Hispanic, and NH White participants (n=8,681). We will use the experiences of discrimination scale score for individual level racism, and derive six measures of structural racism: residential segregation, income, immigrant political climate, political participation, judicial treatment, and homeownership. We will study within-racial and ethnic group differences in PTB; and then examine multilevel (the interaction of individual and structural) racism in the whole group to determine if racism explains the excess PTB observed in NH Black and Hispanic women. Aim 2: Characterize the methylome of all NH Black women in the cohort (n=1,306). We will conduct an epigenome-wide association study of early pregnancy and study candidate genes on stress pathways leading to PTB. Aim 3: Identify whether DNA methylation mediates the association between multilevel racism and PTB among NH Black women (n=1,306). Aims 2 and 3 focus on NH Black women as they bear the highest burden of PTB. This study will be the largest to examine multilevel racism factors and epigenomics in pregnancy among NH Black women. Findings will address knowledge gaps by 1) contributing epigenomic data towards discovery of mechanisms underlying PTB and other adverse birth outcomes in Black women; and 2) informing health policy development related to racism and perinatal health inequities across diverse geographic locations in the U.S.

早产（PTB）是围产期发病率和死亡率的主要原因，两者都有长期后遗症 母亲和婴儿尽管有许多已知的PTB风险因素，但预防和治疗选择有限。 非西班牙裔（NH）黑人女性患PTB的可能性是NH白色女性的2 - 3倍， 一些西班牙裔女性的亚群也有增加的风险。种族主义被认为是 美国围产期健康不公平的原因，但其机制仍然研究不足。 表观遗传学是一个很有希望了解种族主义如何影响基因表达和识别 有色人种妇女的不良生育结果风险。大多数关于怀孕期表观基因组学的研究 新罕布什尔州黑人和西班牙裔女性的代表性较低，而且很少有人将结构性种族主义风险纳入其中。 此外，缺乏从早期妊娠到分娩结局的前瞻性分析，限制了高风险妊娠的识别。 改善产前监测的风险妇女。我们建议通过以下方式解决这些关键的知识差距： 利用迄今为止规模最大、表型最好的队列之一nuMoM2b研究（2010 - 2015）， 一项在美国未产妇中进行的多中心纵向队列研究。 研究包括：从血液中提取母亲DNA，克里格的个人歧视经历， 地理编码的参与者地址、怀孕并发症和分娩结果。我们组建了一个 多学科团队，具有产妇压力，表观基因组学和围产期健康不平等方面的专业知识， 完成三个目标。目标1：确定个人和结构层面的种族主义对PTB的相互影响 在NH黑人、西班牙裔和NH白色参与者中（n = 8，681）。我们将利用 歧视量表得分为个人层面的种族主义，并得出六个措施的结构性种族主义：住宅 种族隔离、收入、移民政治气候、政治参与、司法待遇和住房所有权。 我们将研究PTB的种族和种族内差异，然后检查多水平（ 个人和结构）种族主义，以确定种族主义是否解释了在整个群体中观察到的过度PTB。 黑人和西班牙裔妇女。目的2：表征队列中所有NH黑人女性的甲基化组 （n = 1 306）。我们将对早孕和研究候选人进行表观基因组关联研究。 导致PTB的应激途径基因。目的3：确定DNA甲基化是否介导了这种关联 多层次的种族主义和PTB之间的NH黑人妇女（n = 1，306）。目标2和3侧重于NH Black 妇女是肺结核的最大负担者。这项研究将是最大的审查多层次的种族主义 因素和表观基因组学在NH黑人妇女怀孕。调查结果将通过以下方式解决知识差距：1） 为发现PTB和其他不良出生的潜在机制提供表观基因组数据 黑人妇女的结果;和2）告知与种族主义和围产期健康有关的卫生政策制定 美国不同地理位置的不平等。