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。

基本信息

批准号：
10293757
负责人：
S. Alexandra Burt
金额：
$ 60.32万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10293757
关键词：
Adolescence Adolescent Area Base Sequence Behavior Behavioral Mechanisms Biological Biological Assay Blood Child Rearing Communities 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 Violence Work Youth antisocial behavior early adolescence epigenome indexing infancy methylome methylomics middle childhood neighborhood disadvantage postnatal development predictive marker prospective response social violence exposure

项目摘要

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.

抽象的邻里劣势是青少年冒险行为和攻击性反社会行为的有力预测因素行为（ASB）。这种与青少年 ASB 的关联在生命早期就出现，并随着时间的推移而增强。了解邻里劣势如何导致青少年 ASB 从而构成批判性公众健康需要。然而，迄今为止，劣势影响的生物机制青年 ASB 仍不清楚。拟议的 R01 将探索甲基化作为关键的生物途径邻里劣势与青年 ASB 之间的关联。我们特别假设邻里劣势及其社会和身体“积极成分”（例如严酷的环境）养育子女、接触社区暴力和接触有毒物质）将通过以下方式预测青少年 ASB：甲基组学的改变，并且这些关联将在任何遗传混淆中持续存在。到检查这种可能性，我们将从四点的血液和/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、青春期早期和中期）居住在中度至重度贫困地区的 500 对青少年双胞胎（1,000 对双胞胎）样本社区。然后我们建议在独立样本中复制表型关联 237 名生活贫困的单身青年在三岁时从血液和/或唾液中获得甲基化数据评估波（新生儿、儿童中期和青春期中期）。作为我们的最后一步，我们将利用我们对发现双胞胎样本中双胞胎的关注来评估是否复制了甲基组关联起源于环境和/或遗传。简而言之，拟议的 R01 将不仅可以识别两个独立样本中邻域诱导的甲基组改变贫困青年，但也将阐明这些人的环境和/或遗传病因重复的改变。这样，我们将推动社会和环境表观遗传学领域的发展并在多个领域取得进展。