We propose to use an augmented twin study to understand how genes and environmental risks contribute to vulnerability to drug abuse and antisocial behavior. We will study the impact risks 1) during the early childhood period and 2) during the transition to adolescence. Our focus will be on dimensional indicators of vulnerability. The traditional twin study design will be augmented by 1) combined analyses of data from twin pairs tested in this component and data from adoption and biological siblings. 2) inclusion in the study of a nearest age sibling, and 3) confirmatory QTL analyses to determine how genetic risk factors are mediated. 400 pairs of twins (aged 12 years), who have been assessed on a wide range of measures of psychosocial adjustment and competence, temperament, affect, school achievement and cognitive abilities, family environment, and health, at regular intervals since infancy, are now entering the period of risk for the onset of drug use and antisocial behavior. Using dimensional indices related to outcome, this sample offers a unique opportunity to identify the very earliest genetic and environmentally influenced risk factors for the onset of drug use and antisocial behavior. 1000 newly ascertained twin pairs will be recruited to match the age range of the adolescent assessments in the ongoing Colorado Adoption Project (12-16 years). Multivariate genetic analysis will enable us to identify genetic and environmentally mediated associations between risks for antisocial conduct, early drug experimentation, and progression to regular drug use or abuse in a community sample. We will collect DNA from all participating individuals and their parents using non-invasive oral collection methods. DNA will be extracted and stored for later use. Given successful identification of a small number of candidate regions for QTL influencing vulnerability to drug abuse, we will be able to explore their possible mechanisms of action. We will have an effective sample of approximately 1695 dizygotic twin and biological sibling pairs for whom we have extensive standardized phenotypic information on dimensional indices of vulnerability. This sample may be used to determine the likely mediation of the QTL effects during infancy, early childhood, and adolescence.
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