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.
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