Statistical methods to localize disease heritability and identify biological mechanisms

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PROJECT SUMMARY/ABSTRACT Schizophrenia is a psychotic, chronic and disabling disorder, affecting about 1% of the general population. Identifying individuals at risk for developing this disorder is crucial for establishing preventive interventions. So far, the assessment of risk of developing psychosis has been based primarily on clinical features, the accuracy of which is not optimal for development and implementation of preventive interventions. Evaluation of psychosis risk improves when genetic risk is taken into account. Thus, development of robust measure of genetic risk for psychosis offers a possibility of improvement in assessment of psychosis risk. Recent success of genome- wide association studies in schizophrenia allows the calculation of a polygenic risk score that reflects a cumulative impact of common genetic variants on the development of the disorder and related phenotypes. The aim of this study is to examine the performance of such schizophrenia polygenic score on evaluation of psychosis risk in a sample of individuals at high risk of developing psychosis based on clinical features. The examination will extend to the performance of the genetic score in individuals of non-European descent. This will advance our tools for identification of psychosis risk and, consequently, its preventive interventions in diverse populations.