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，并且会造成长期后遗症 尽管有许多已知的 PTB 危险因素，但预防和治疗选择仍然有限。 非西班牙裔 (NH) 黑人女性患 PTB 的可能性是 NH 白人女性的 2-3 倍， 西班牙裔女性的一些亚群体也被当作种族主义被利用的风险增加的根源。 造成美国围产期健康不平等的原因，但其机制仍未得到充分研究。 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并识别种族歧视的领域。 大多数妊娠期表观基因组学研究都发现了有色人种女性不良分娩结果的风险。 新罕布什尔州黑人和西班牙裔女性的代表性较低，而且很少包含结构性种族主义暴露。 此外，缺乏从妊娠早期到出生结果的前瞻性分析，限制了高风险人群的识别。 我们建议通过以下方式解决这些关键的知识差距。 nuMoM2b 研究（2010-2015 年）利用迄今为止规模最大、表型最好的队列之一， 对美国各地未产孕妇进行的多中心、队列纵向研究 现有数据 研究内容包括：从血液中提取母体DNA、克里格个人遭受歧视的经历、 我们已经对参与者地址、妊娠并发症和出生结果进行了地理编码。 多学科团队在孕产妇压力、表观基因组学和围产期健康不平等方面拥有专业知识， 完成三个目标 1：确定个人和结构层面的种族主义对 PTB 的交互影响。 我们将利用 NH 黑人、西班牙裔和 NH 白人参与者（n=8,681）的经验。 个人层面种族主义的歧视量表得分，并得出结构性种族主义的六种衡量标准：居住 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 中的种族和民族差异，然后研究多层次的（相互作用）； 整个群体中的个人和结构）种族主义，以确定种族主义是否解释了在 NH 黑人和西班牙裔女性 目标 2：描述队列中所有 NH 黑人女性的甲基化组特征。 (n=1,306) 我们将对早期妊娠和研究候选者进行全表观基因组关联研究。 目标 3：确定 DNA 甲基化是否介导这种关联。 NH 黑人女性中的多层次种族主义和 PTB 之间的关系（n=1,306）目标 2 和 3 重点关注 NH 黑人。 女性承受着最严重的 PTB 负担。这项研究将是调查多层次种族主义的最大规模的研究。 新罕布什尔州黑人女性怀孕的因素和表观基因组学研究结果将解决以下方面的知识差距：1) 为发现 PTB 和其他不良分娩的机制贡献表观基因组数据 黑人妇女的结果；2) 为与种族主义和围产期健康相关的卫生政策制定提供信息 美国不同地理位置的不平等