Epigenetic Mediation of Adverse Social Context on Stress Response, Socioemotional Development, and Health in a Population-based Study of Minority and Low SES Children and Adolescents

工程摘要 儿童和青少年在一系列健康问题上存在明显的种族、民族和社会经济地位差异， 许多成年人的健康差距可以追溯到儿童时期的社会背景不平等。 表观遗传学--对基因组进行的不改变核苷酸序列的修饰--有很大的希望 作为背景效应和健康状况的潜在指标， 才能被正常观察到在现有的一项关于儿童的代表性研究的基础上，这项建议将 通过以下方式直接响应PAR-16-355：1）收集2,000名儿童在两个时间点的表观基因组数据， 时间，2）描述3个种族/种族组和SES水平的甲基化模式，以及3）解释 表观遗传与社会逆境，生物过程和社会情感发展的联系。的 总体假设是DNA甲基化部分介导了不利的社会环境的影响（即， 贫困，严厉的养育，邻里混乱，家庭不稳定，和父母监禁） 与压力反应相关的生物学过程（端粒长度和磨损，皮质醇反应，DHEA水平） 和压力反应行为（行为问题，冒险和弹性）。我们进一步假设 种族/民族和SES对逆境的不同暴露和不同反应解释了一些 压力反应和社会情绪发展的差异，因此需要正式比较 种族/民族和SES在同一研究中。为了进行这项研究，我们利用脆弱家庭和儿童 幸福研究（FFCWS）：一项全国20个城市和城市代表性样本，包括1998年出生的4898名儿童， 2000. FFCW提供了非西班牙裔黑人（47%），西班牙裔（27%）和 贫困家庭，使数据特别有用的研究种族/民族和社会经济地位的差异。 家庭在出生时和1岁，3岁，5岁，9岁和15岁时接受了采访，并在9岁和15岁时收集了生物数据。 15.预期的结果将提供估计：1）基于群体的表观基因组范围的DNA 3个人种/种族组的甲基化测量（西班牙裔n=600，非洲血统n=980，欧洲血统 n=420）在儿童和青少年，2）协会的社会逆境跨越发展（从子宫内到 15岁）与DNA甲基化，3）DNA甲基化和压力的生物措施之间的关联 反应（即端粒长度和磨损，皮质醇反应和DHEA水平），4）协会 应激反应行为的发展与甲基化谱之间的关系，以及5）所有这些的比较 3个种族/民族群体和广泛的社会经济地位之间的关系。

Project Abstract Pronounced disparities exist by race, ethnicity, and SES in children and adolescents across a range of health conditions, and many adult health disparities can be traced to childhood social contextual inequalities. Epigenetics—modifications to the genome that are not changes in nucleotide sequence—holds great promise as potential indicators of contextual effects and health condition, potentially uncovering health disparities long before they are normally observable. Building on an existing representative study of children, this proposal will directly respond to PAR-16-355 by: 1) assembling epigenome-wide data on 2,000 children at two points in time, 2) describing methylation patterns in 3 race/ethnic groups and across SES levels, and 3) explicating epigenetic associations with social adversity, biological processes, and socioemotional development. The overarching hypothesis is that DNA methylation partially mediates the effect of adverse social context (i.e. poverty, harsh parenting, neighborhood disorganization, family instability, and parental incarceration) on biological processes related to stress response (telomere length and attrition, cortisol response, DHEA levels) and stress responsive behaviors (behavioral problems, risk taking, and resilience). We further hypothesize both differential exposure and differential response to adversity by race/ethnicity and SES explains some of the disparity in stress response and socioemotional development—thereby requiring formal comparisons of race/ethnicity and SES in the same study. To conduct this research we utilize the Fragile Families and Child Wellbeing Study (FFCWS): a 20-city nationally and city representative sample of 4898 children born in 1998- 2000. FFCW provides a uniquely high prevalence of non-Hispanic Black (47%), Hispanic (27%), and impoverished families, making the data particularly useful for studying race/ethnic and SES differences. Families were interviewed at birth and at ages 1, 3, 5, 9, and 15—with biological data collected at ages 9 and 15. The expected results will be to provide estimates of: 1) population-based epigenome-wide DNA methylation measures for 3 race/ethnic groups (Hispanic n=600, African ancestry n=980, European ancestry n=420) in childhood and adolescence, 2) associations of social adversity across development (from in utero to age 15) with DNA methylation, 3) associations between DNA methylation and biological measures of stress response (i.e. telomere length and attrition, cortisol response, and DHEA levels), 4) associations between development of stress response behaviors and methylation profiles, and 5) comparisons of all these relationships in 3 race/ethnic groups and across a wide range of SES.