The methylomic consequences of neighborhood disadvantage for youth risk-taking behaviors.

邻里劣势对青少年冒险行为的甲基组学后果。

• 批准号: 10625540
• 负责人: S. Alexandra Burt
• 金额: $ 57.85万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-20 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625540
• 关键词: Adolescence; Adolescent; Area; Base Sequence; Behavior; Biological; Biological Assay; Blood; Child Rearing; Cotinine; DNA; DNA Methylation; Data; Development; Developmental Process; Disadvantaged; Dizygotic Twins; Elements; Environment; Environmental Exposure; Epigenetic Process; Etiology; Exposure to; Genetic; Genetic Predisposition to Disease; Genome; Human; Individual; Lead; Life; Link; Longitudinal Studies; Mediating; Mediator; Methylation; Modification; Monozygotic twins; Neighborhoods; Neonatal; Neurotoxins; Pathway interactions; Peripheral; Phenotype; Poverty; Public Health; Risk; Risk Taking; Saliva; Salivary; Sampling; Site; Source; Spottings; Time; Tissues; Toxicant exposure; Twin Multiple Birth; Twin Studies; United States; Variant; Work; Youth; antisocial behavior; community violence; early adolescence; epigenome; indexing; infancy; methylome; methylomics; middle childhood; neighborhood disadvantage; postnatal development; predictive marker; prospective; response; social; violence exposure

ABSTRACT Neighborhood disadvantage is a potent predictor of youth risk-taking and aggressive antisocial behaviors (ASB). This association with youth ASB emerges early in life and increases over time. Understanding how neighborhood disadvantage leads to youth ASB thus constitutes a critical public health need. To date, however, the biological mechanism(s) through which disadvantage influences youth ASB remain unclear. The proposed R01 will explore methylation as a key biological pathway underlying the association between neighborhood disadvantage and youth ASB. We specifically postulate that neighborhood disadvantage and its social and physical `active ingredients' (e.g., harsh parenting, exposure to community violence, and toxicant exposure) will predict youth ASB via methylomic alterations, and that these associations will persist over any genetic confounds. To examine this possibility, we will generate methylation data from blood and/or saliva at four assessment waves (neonatal, middle childhood, and early and mid-adolescence) in a discovery sample of 500 adolescent twin pairs (1,000 twins) residing in modestly-to-severely disadvantaged neighborhoods. We then propose to replicate the phenotypic associations in an independent sample of 237 singleton youth living in poverty with methylation data from blood and/or saliva at three assessment waves (neonatal, middle childhood, and mid-adolescence). As our final step, we will leverage the focus on twin pairs in our Discovery twin sample to evaluate whether the replicated methylomic associations are environmental and/or genetic in origin. In short, the proposed R01 will not only identify neighborhood-induced methylomic alterations in two independent samples of impoverished youth, but will also illuminate the environmental and/or genetic etiology of those replicated alterations. In this way, we will move the field of social and environmental epigenetics forward in several areas.

摘要 社区劣势是年轻人冒险和激进反社会行为的有力预测因素 行为(ASB)。这种与青年ASB的联系在生命早期就出现了，并随着时间的推移而增加。 理解邻里劣势如何导致年轻人ASB因此构成了一个批判性的公众 健康需要。然而，到目前为止，不利因素影响的生物机制(S) 青年ASB仍不清楚。建议的R01将探索甲基化作为关键的生物途径 社区劣势与青年ASB之间的关联。我们特别指出 假定邻里劣势及其社会和物质上的“积极因素”(例如，苛刻 养育子女、接触社区暴力和接触毒物)将通过以下方式预测青少年ASB 甲基组改变，并且这些关联将在任何遗传混淆中持续存在。至 研究这种可能性，我们将在4点从血液和/或唾液中产生甲基化数据 一项发现中的评估浪潮(新生儿、童年中期、青春期早期和中期) 居住在中等到严重贫困地区的500对青少年双胞胎(1000对双胞胎)的样本 邻里关系。然后我们建议在一个独立的样本中复制表型关联 237名独生子女青年生活在贫困中，他们的血液和/或唾液甲基化数据只有3岁 评估波(新生儿、儿童期中期和青春期中期)。作为最后一步，我们将 利用我们的Discovery双胞胎样本中对双胞胎的关注来评估复制的 甲基组关联源于环境和/或遗传。简而言之，拟议的R01将 不仅在两个独立的样本中识别邻居诱导的甲基化改变 但也将阐明这些贫困青年的环境和/或遗传病因 复制的更改。通过这种方式，我们将推动社会和环境表观遗传学领域 在几个方面向前迈进。