Reciprocal Genetic-Environmental Interactions During Childhood and Adolescence

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的相互作用的理解。然而，在这些研究中发现的遗传信息通常限于固定的遗传特征（即DNA序列和遗传特征）。 其变体）。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。该提案旨在寻求资金，以检查脆弱家庭和儿童福祉研究（FFCWS）中儿童和青少年参与者中TL和DM的水平和变化，并确定这些可变遗传特征的早期社会环境预测因子。该FFCWS是独特的定位，以促进我们的社会环境对幼儿的可变遗传特征的影响的理解。FFCWS在过去十年中已经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岁时收集的唾液中测定儿童的TL和DM，并通过用定制阵列（72个基因，200个SNP变体）重新分析9年的DNA来显著扩大固定DNA标记物的数量，所述定制阵列包括与神经发育、多巴胺能、多巴胺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 - 15岁之间的端粒长度和端粒长度变化，（B）9 - 15岁之间的DNA甲基化和DNA甲基化变化，以及（c）固定的遗传变异（即SNP）。 3)探讨儿童遗传差异敏感性与社会环境的交互作用对端粒长度和DNA甲基化的影响。 4)通过额外进行250次青少年面对面访谈，加强NICHD资助的15年FFCWS调查中的模式实验。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测定DM和TL。我们希望在9至15岁之间发现TL和DM的显着变化。一些变化将是由于时间和发展，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性状。随着端粒和甲基化数据添加到FFCWS中，它将成为目前可用于联合收割机的唯一数据集：1）基于人群的设计，2）关于儿童自出生以来的丰富详细的纵向数据，3）特别大暴露于恶劣环境的样本，4）重要神经递质、神经发育和相关系统的DNA标记，和5）在两个时间点测量端粒长度和DNA甲基化。因此，这项研究中收集的数据将允许对基因，环境和健康的相互作用进行一些新的探索。! !

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. ! !