Uncovering and confirming gene-environment interactions in psychopathology

描述(申请人提供)：揭示和证实应激相关精神病理学中的基因-环境相互作用。这项拟议的研究将汇集3项纵向队列研究(包括4个队列样本)，以创建一个强大的流行病学资源，用于测试关于基因-环境相互作用(GxE)的假设，并复制这些发现。利用这一多项研究资源，我们试图通过研究一组候选基因来确定抗应激的遗传途径，这些候选基因被假设为缓和心理社会应激源(虐待、暴力受害、应激性生活事件)对行为障碍和抑郁/焦虑障碍的影响。方法：3项纵向队列研究(包括4个队列样本，5000人)分别是：达尼丁多学科健康与发展研究、克赖斯特彻奇健康与发展研究和行为发育环境风险研究。这一流行病学资料将包括4个必要要素：(A)四个具有人口代表性的样本；(B)关于多个发展阶段环境暴露的可比信息(例如，儿童期虐待；暴力受害；应激性生活事件)；(C)精神结果的衡量；(D)DNA。这一资源将用于对不同样本进行假设驱动的GxE研究，并通过进行交叉研究复制测试来确定结果的重复性。贡献与意义：拟议的研究可以通过确定应激相关精神病理学中可复制的GxE交互作用，并为应激抵抗与脆弱性的心理生物学机制的理论发展奠定基础，从而做出重要的翻译贡献。

DESCRIPTION (provided by applicant): Uncovering & confirming gene-environment interactions in stress-related psychopathology. The proposed research will to bring together 3 longitudinal cohort studies (comprising 4 cohort samples) in order to create a powerful epidemiological resource for testing hypotheses about gene- environment interaction (GxE), and for replicating these findings. Using this multi-study resource, we seek to identify genetic pathways of stress resistance by studying sets of candidate genes that are hypothesized to moderate the effects of psychosocial stressors (maltreatment, violence victimization, stressful life events) on conduct disorder and depression/anxiety disorders. Methods: The 3 longitudinal cohort studies (comprising 4 cohort samples, with 5000 individuals) are: the Dunedin Multidisciplinary Health and Development Study, the Christchurch Health and Development Study, and the Environmental Risk Study of Behavioral Development. This epidemiological resource will have 4 necessary elements: (a) Four population-representative samples; (b) comparable information about environmental exposures at multiple points in development (e.g., childhood maltreatment; violence victimization; stressful life events); ( c) measures of psychiatric outcomes; and (d) DNA. This resource will be used to carry out hypothesis-driven studies of GxE across different samples and to establish the reproducibility of the results by carrying out cross-study replication tests. Contributions & Significance: The proposed research can make an important translational contribution by identifying replicable GxE interactions in stress-related psychopathology and by laying a foundation for theory development about psychobiological mechanisms in stress resistance versus vulnerability.