Uncovering and confirming gene-environment interactions in psychopathology

描述（由申请人提供）：发现并确认压力相关精神病理中基因与环境的相互作用。拟议的研究将汇集3个纵向队列研究（包括4个队列样本），以创建一个强大的流行病学资源，用于测试基因-环境相互作用（GxE）的假设，并复制这些发现。利用这一多重研究资源，我们试图通过研究一系列候选基因来确定抗逆性的遗传途径，这些候选基因被假设为调节社会心理压力源（虐待、暴力受害、压力生活事件）对品行障碍和抑郁/焦虑症的影响。方法：3项纵向队列研究（包括4个队列样本，共5000人）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展的环境风险研究。这种流行病学资源将包括四个必要要素：(a)四个具有人口代表性的样本；(b)关于发育过程中多个阶段环境暴露的可比信息（例如，童年虐待、暴力受害、生活压力事件）；(c)精神病治疗结果的测量；(d) DNA。该资源将用于对不同样本的GxE进行假设驱动的研究，并通过进行交叉研究复制测试来确定结果的可重复性。贡献与意义：本研究发现了应激相关精神病理中可复制的GxE相互作用，为应激抵抗与易损性的心理生物学机制的理论发展奠定了基础，具有重要的翻译贡献。

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.