Reciprocal Genetic-Environmental Interactions During Childhood and Adolescence

童年和青少年时期遗传与环境的相互相互作用

• 批准号: 8707246
• 负责人: DANIEL A. NOTTERMAN
• 金额: $ 76.69万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8707246
• 关键词: Adolescence; Adolescent; Adult; Affect; Age; Animal Model; Behavior; Biological; Biological Assay; Birth; Characteristics; Child; Child health care; Childhood; Custom; DNA; DNA Markers; DNA Methylation; DNA Sequence; Data; Data Collection; Data Set; Development; Economically Deprived Population; Effectiveness; Environment; Environmental Risk Factor; Epigenetic Process; Exposure to; Family; Funding; Future; Gender; Genes; Genetic; Genetic Polymorphism; Genome; Genotype; Health; Health behavior; Individual; Interview; Length; Letters; Life; Mails; Measures; Methylation; Minority; Modeling; National Institute of Child Health and Human Development; Neurotransmitters; Outcome; Parents; Participant; Pathway interactions; Persons; Population; Positioning Attribute; Procedures; Race; Research Design; Research Personnel; Saliva; Sampling; Shapes; Social Environment; Source; Surveys; System; Time; Variant; Work; base; child poverty; design; early adolescence; genetic variant; infancy; population based; public health relevance; research study; social; socioeconomics; telomere; trait

DESCRIPTION (provided by applicant): Recent efforts to add genetic data to population-based studies have substantially increased our understanding of the interplay of genetic and social environmental factors in shaping health and wellbeing. However, the genetic information found in these studies is typically limited to fixed genetic characteristics (i.e. DNA sequence and its variants). Much less is known about the influence of social environments on variable genetic characteristics such as telomere length (TL) and DNA methylation (DM). This proposal seeks funds to examine levels of and changes in TL and DM among child and adolescent participants in The Fragile Families and Child Wellbeing Study (FFCWS) and to identify early social environmental predictors of these variable genetic characteristics. The FFCWS is uniquely positioned to advance our understanding of the influence of social environments on young children's variable genetic characteristics. The FFCWS has emerged over the past decade as a leading source of information about the social environment and its influence on child health and wellbeing. Four aims are: 1) To assay TL and DM for children from saliva collected at ages 9 and 15 and to substantially expand the number of fixed DNA markers by reanalyzing 9-year DNA with a custom array (72 genes, 200 SNP variants) that includes genes related to neurodevelopmental, dopaminergic, serotonergic and other behaviorally-relevant pathways. 2) To examine the interaction between the social environment from infancy through early adolescence and: (a) telomere length and changes in telomere length between ages 9 and 15, (b) DNA methylation and changes in DNA methylation between ages 9 and 15, and (c) fixed genetic variants (i.e. SNPs). 3) To examine the influence of the interaction of children's measured genetic differential sensitivity and their social environment on telomere length and DNA methylation. 4) To strengthen the mode experiment in the NICHD funded 15-year FFCWS survey by conducting an additional 250 in-person adolescent interviews. DM and TL will be assayed using saliva samples collected in the year 9 data collection and the year 15 data collection. We expect to find significant changes between ages 9 and 15 in both TL and DM. Some of the change will be due to time and development while other changes are expected to follow the animal model findings that family social environment significantly influences variable genetic traits. With the addition of telomere and methylation data to FFCWS, it will be the only data set currently available to combine: 1) a population-based design, 2) richly detailed longitudinal data on the child since birth, 3) a sample with especially large exposure to harsh environments, 4) DNA markers on important neurotransmitter, neurodevelopmental, and related systems, and 5) telomere length and DNA methylation measures at two time points. Thus data gathered in this study will allow for several new explorations into the interplay of genes, environment, and health. ! !

描述（由申请人提供）：最近将遗传数据添加到基于人群的研究中的努力大大增加了我们对遗传和社会环境因素在塑造健康和福祉方面相互作用的理解。然而，这些研究中发现的遗传信息通常仅限于固定的遗传特征（即 DNA 序列和 它的变体）。关于社会环境对端粒长度 (TL) 和 DNA 甲基化 (DM) 等可变遗传特征的影响知之甚少。该提案寻求资金来检查脆弱家庭和儿童福祉研究 (FFCWS) 中儿童和青少年参与者的 TL 和 DM 水平和变化，并确定这些可变遗传特征的早期社会环境预测因子。 FFCWS 具有独特的优势，可以促进我们了解社会环境对幼儿可变遗传特征的影响。 FFCWS 在过去十年中已成为有关社会环境及其对儿童健康和福祉影响的主要信息来源。四个目标是：1) 从 9 岁和 15 岁收集的儿童唾液中检测 TL 和 DM，并通过使用定制阵列（72 个基因，200 个 SNP 变体）重新分析 9 岁 DNA 来大幅扩展固定 DNA 标记的数量。包括与神经发育、多巴胺能、血清素能和其他行为相关途径相关的基因。 2) 研究从婴儿期到青春期早期的社会环境与以下因素之间的相互作用：(a) 9 至 15 岁之间的端粒长度和端粒长度的变化，(b) 9 至 15 岁之间的 DNA 甲基化和 DNA 甲基化的变化，以及(c) 固定遗传变异（即 SNP）。 3) 检验儿童测量的遗传差异敏感性与其社会环境的相互作用对端粒长度和DNA甲基化的影响。 4) 通过额外进行 250 名青少年面对面访谈，加强 NICHD 资助的 15 年 FFCWS 调查的模式实验。将使用第 9 年数据收集和第 15 年数据收集中收集的唾液样本对 DM 和 TL 进行测定。我们预计 9 岁至 15 岁之间的 TL 和 DM 都会发生显着变化。一些变化是由于时间和发育造成的，而其他变化预计将遵循动物模型的发现，即家庭社会环境显着影响可变的遗传特征。随着 FFCWS 中添加端粒和甲基化数据，它将成为目前唯一可以结合以下内容的数据集：1) 基于人群的设计，2) 自出生以来儿童的详细纵向数据，3) 特别大的样本暴露于恶劣环境，4) 重要神经递质、神经发育和相关系统上的 DNA 标记，以及 5) 两个时间点的端粒长度和 DNA 甲基化测量。因此，本研究收集的数据将有助于对基因、环境和健康之间的相互作用进行一些新的探索。 ！ ！