We will study a relatively genetically homogeneous population to test the hypotheses that genetic factors are linked to schizophrenia. The study will focus on two populations. The first is from the Azores, a nine island archipelago in the Atlantic ocean that is a Portuguese state. The Azores have a centralized health system. All ten psychiatrists on the islands are collaborating with us on this project. The second population is from continental Portugal. The majority of the Azorean population is derived from this population base. Families with multiple affected members with schizophrenia, will be studied employing both parametric and non-parametric analytic strategies. We projected approximately 100 families segregating for schizophrenia, including over 300 affected family members. A complementary strategy will be used to study candidate loci. We will study a sample of 225 subjects suffering from schizophrenia and their parents (Total n=675) employing the haplotype relative risk and the transmission/disequilibrium test strategies. This strategy insures that we control for all ancestry for each subject, using the uninherited haplotype derived from the two parents. The third sample will include all other Azorean patients with schizophrenia, who agreed to participate in hopefully, achieving close to complete ascertainment of patients with schizophrenia in the Azores. This will be a valuable sample for linkage disequilibrium approaches given the nature of the Azorean population and provide us with a unique epidemiologic frame. These complementary strategies will allow us to cross validate any positive results. The careful diagnostic definition of phenotype will be based on detailed structured clinical data employing the Diagnostic Interview for Genetic Studies (DIGS), which we have translated into Portuguese. Our project is designed to capture a very complete history of the patients illness, as well as to be able to follow most subjects prospectively for a long period of time. This will be extremely valuable for achieving diagnostic certainty and minimizing false positives. An important new addition to this proposal is the Whitehead/MIT Center for Genome Research, that will perform a genome-wide scan and collaborate on all data analysis for the project.
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