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: 10454231
• 负责人: S. Alexandra Burt
• 金额: $ 57.58万
• 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/10454231
• 关键词: Adolescence; Adolescent; Area; Base Sequence; Behavior; Behavioral Mechanisms; 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 of activation protein; Methylation; Modification; Monozygotic twins; Neighborhoods; Neonatal; Neurotoxins; Pathway interactions; Peripheral; Phenotype; Poverty; Public Health; Risk; Risk-Taking; Saliva; Salivary; Sampling; Site; Source; 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 邻里劣势是青少年冒险和攻击性反社会的有力预测因素 行为（ASB）。这种与青少年ASB的联系在生命早期出现，并随着时间的推移而增加。 了解邻里劣势如何导致青年ASB，从而构成了一个关键的公众 健康需要。然而，到目前为止，不利影响的生物机制 青少年ASB仍不清楚。拟议的R 01将探索甲基化作为一个关键的生物学途径 潜在的邻里劣势和青年ASB之间的关联。我们特别 假设邻里的不利条件及其社会和物理“活性成分”（例如，恶劣 父母养育，暴露于社区暴力和有毒物质暴露）将通过以下方式预测青年ASB： 甲基化改变，这些协会将持续任何遗传混乱。到 为了检验这种可能性，我们将在四个月内从血液和/或唾液中生成甲基化数据， 发现中的评估波（新生儿、儿童中期、青少年早期和中期） 500对青少年双胞胎（1,000对双胞胎）的样本，居住在中度至重度贫困地区， 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名单身青年生活在贫困中，他们的血液和/或唾液中的甲基化数据在三岁时 评估波（新生儿、儿童中期和青春期中期）。作为最后一步，我们将 利用我们的发现双胞胎样本中对双胞胎对的关注， 甲基化组关联是环境和/或遗传起源的。简而言之，拟议的R 01将 不仅在两个独立的样本中鉴定了邻居诱导的甲基化改变， 贫困青年，但也将阐明环境和/或遗传病因，这些 复制的改变。通过这种方式，我们将社会和环境表观遗传学领域 在几个领域取得进展。