Epigenomic Pathways from Racism to Preterm Birth

早产是围产儿发病率和死亡率的主要原因，两者都有长期的后遗症。 母亲和婴儿。尽管有许多已知的肺结核危险因素，但预防和治疗选择有限。 非西班牙裔黑人女性患肺结核的可能性是白人女性的2-3倍， 西班牙裔女性的一些亚群也增加了风险。种族主义被认为是根源 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和识别 有色人种妇女中不良生育结局的风险。大多数关于妊娠表观基因组学的研究都有 NH黑人和西班牙裔妇女的代表性很低，很少有结构性种族主义暴露。 此外，缺乏从早孕到分娩结局的前瞻性分析，限制了对高危人群的识别。 对妇女进行改进产前监测的风险。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)， 美国各地未分娩孕妇的多中心纵向队列研究现有数据 研究内容包括：从血液中提取母体DNA，克里格的个人歧视经历， 地理编码的参与者地址、妊娠并发症和出生结局。我们已经组建了一支 拥有母亲压力、表观基因组学和围产期健康不平等方面的专业知识的多学科团队 完成三个目标。目标1：确定个人层面和结构层面的种族主义对肺结核的交互影响 在NH Black、西班牙裔和NH White参与者中(n=8,681)。我们将利用 个人层面种族主义的歧视量表得分，并推导出结构性种族主义的六个衡量标准：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。 我们将研究结核分枝杆菌的种族内和民族差异；然后考察多层面( 个人的和结构性的)种族主义，以确定种族主义是否可以解释#年观察到的过度肺结核 NH黑人和西班牙裔女性。目标2：描述队列中所有NH黑人女性的甲基组 (n=1306)。我们将进行一项表观基因组与早孕的关联研究，研究对象为 导致肺结核的应激途径上的基因。目标3：确定DNA甲基化是否介导了这种联系 NH黑人妇女中多层次种族主义与肺结核之间的关系(n=1,306)。目标2和目标3专注于NH Black 女性，因为她们承担着最高的肺结核负担。这项研究将是考察多层次种族主义的最大规模的研究 NH黑人妇女怀孕的影响因素和表观基因组学。调查结果将在1年前解决知识差距问题 有助于发现肺结核和其他不利出生的机制的表观基因组数据 黑人妇女的结果；和2)为与种族主义和围产期健康有关的卫生政策发展提供信息 美国不同地理位置的不平等

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.