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，长期后遗症 母亲和婴儿。尽管PTB有许多已知的危险因素，但预防和治疗方案仍有限。 与NH白人妇女相比，非西班牙裔（NH）黑人妇女经历PTB的可能性高2-3倍 一些西班牙裔妇女的亚组也增加了风险。种族主义已被认为是根源 美国（美国）围产期健康不平等的原因，但其机制仍被理解。 表观遗传学是一个有很大希望的领域，可以理解种族主义如何影响基因表达和识别 有色女性的不良出生结果的风险。大多数对怀孕表观基因组学的研究已经 NH Black和西班牙裔妇女的代表性低，很少有人包括结构性种族主义。 此外，缺乏从怀孕早期到出生结局的前瞻性分析，限制了高度的鉴定 风险妇女有改善产前监测的风险。我们建议通过 利用迄今为止最大，最优秀的人群之一，NUMOM2B研究（2010- 2015年），A 美国现有数据的多中心，纵向队列研究。 研究包括：从血液中提取的母校DNA，克里格的个人歧视经历， 地理编码的参与者讲话，妊娠并发症和出生结果。我们已经组装了 多学科团队具有遗物压力，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：确定个体和结构水平种族主义对PTB的互动效果 在NH Black，西班牙裔和NH白人参与者中（n = 8,681）。我们将利用 个人级别种族主义的歧视量表得分，并得出了六个结构性种族主义的措施：居民 种族隔离，收入，移民政治气候，政治参与，司法待遇和房屋所有权。 我们将研究PTB内种族和种族群体的差异；然后检查多级（相互作用 整个群体中的个人和结构性种族主义，以确定种族主义是否解释了在 NH Black和西班牙裔妇女。 AIM 2：表征同类中所有NH黑人妇女的甲基团 （n = 1,306）。我们将对早期妊娠和研究候选者进行一项表观基因组的关联研究 应力途径的基因导致PTB。目标3：确定DNA甲基化是否介导了缔合 在NH黑人妇女中，多级种族主义和PTB之间（n = 1,306）。目标2和3专注于NH黑色 妇女承担PTB的最高负担。这项研究将是研究多层次种族主义的最大 NH黑人妇女怀孕的因素和表观基因组学。调查结果将通过1）解决知识差距。 为发现PTB和其他不良出生的机制的发现贡献表观基因组学数据 黑人妇女的结果； 2）告知与种族主义和围产期健康有关的健康政策制定 美国潜水员地理位置的不平等现象