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

在少数民族和低社会经济地位儿童和青少年的人口研究中，不良社会背景对压力反应、社会情感发展和健康的表观遗传调节

• 批准号: 10162326
• 负责人: COLTER M.S. MITCHELL
• 金额: $ 72.84万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-16 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10162326
• 关键词: 15 year old; 9 year old; Address; Adolescence; Adolescent; Adult; Affect; African; Age; Base Sequence; Behavior; Behavioral; Biological; Biological Assay; Biological Process; Birth; Characteristics; Child; Child Development; Child Rearing; Child Welfare; Childhood; Cities; Cohort Studies; Complex; DNA; DNA Methylation; Data; Development; Epigenetic Process; Ethnic Origin; Ethnic group; European; Exposure to; Family; Genome; Health; High Prevalence; Hispanics; Human; Hydrocortisone; Imprisonment; Inequality; Internet; Interview; Length; Link; Low income; Measurement; Measures; Mediating; Mediation; Methylation; Minority; Modification; Neighborhoods; Not Hispanic or Latino; Outcome; Personal Satisfaction; Population; Population Study; Positioning Attribute; Poverty; Problem behavior; Race; Research; Research Personnel; Risk; Risk-Taking; Sampling; Sampling Studies; Social Change; Social Conditions; Social Environment; Socioeconomic Status; Source; Stress; Testing; Time; Vulnerable Populations; behavior measurement; behavioral health; behavioral response; biological adaptation to stress; cohort; dehydroepiandrosterone; epigenome; genome-wide; health disparity; health disparity populations; in utero; low socioeconomic status; methylation pattern; middle childhood; minority children; population based; resilience; response; social; supportive environment; telomere; tool

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.

项目摘要 种族，种族和SES在一系列健康的儿童和青少年中存在明显的分布 条件和许多成人健康差异可以追溯到儿童时期的社会背景不平等。 表观遗传学 - 对核苷酸序列不变的基因组的修改 - 持有巨大的希望 作为情境影响和健康状况的潜在指标，可能会发现健康差异很长 通常可以观察到它们。在现有的儿童代表性研究的基础上，该建议将 直接回应16-355 PAR 16-355：1）在两个分数中汇编2,000名儿童的表观基因组的数据 时间，2）描述3个种族/种族和跨SES级别的甲基化模式，以及3）明确 与社会广告，生物学过程和社会情感发展的表观遗传学联系。 总体假设是DNA甲基化部分介导了不利社会环境的影响（即 在 与压力反应有关的生物过程（端粒长度和属性，皮质醇反应，DHEA水平） 以及压力响应式行为（行为问题，冒险和韧性）。我们进一步假设 通过种族/民族对广告的差异曝光和差异反应，SES都解释了一些 压力反应和社会情感发展的差异 - 在其中需要正式比较 在同一研究中种族/种族和SES。为了进行这项研究，我们利用脆弱的家庭和孩子 福利研究（FFCWS）：全国20个城市和城市代表样本的4898名儿童出生于1998年 - 2000。FFCW提供了非西班牙裔黑人（47％），西班牙裔（27％）和 贫穷的家庭，使数据对于研究种族/种族和SES差异特别有用。 在出生时和1、3、5、9和15岁时接受了家庭采访。 15。预期的结果将提供：1）基于群体的表观基因组DNA 3种种族/族裔的甲基化度量（西班牙裔n = 600，非洲血统n = 980，欧洲血统 n = 420）在童年和青少年时期，2）跨开发的社交广告的关联（从子宫到子宫到 年龄15）与DNA甲基化，3）DNA甲基化与应激的生物学测量之间的关联 响应（即端粒长度和损耗，皮质醇响应和DHEA水平），4）关联 在压力反应行为的发展和甲基化谱之间，以及5）所有这些的比较 在3个种族/族裔以及各种SES的关系中的关系。