Linkage disequilibrium (LD) analysis has been shown to be an ideal method for mapping complex disease genes in isolated founder populations. This proposal is designed to collect a sample of patients with schizophrenia who are descended from the founder population of Costa Rica, with the goal of mapping and identifying schizophrenia predisposition genes in this country. The Costa Rican population is ideal for this study, because it is a large population descended over 20 generations from a small group of founders, and predisposition genes for bipolar affective disorder have already been mapped in this country. The investigators' sample consists of Costa Rican patients with multiple hospitalizations for acute schizophrenic episodes and with early age of onset. Diagnostic procedures include a blinded interview by a bilingual psychiatrist, using the DIGS (Diagnostic Interview for Genetic Studies), as well as a family history interview, semi-structured collection of medical records, and a best-estimate process. Genealogic workup is done for each proband to document birthplace of ancestors in the great-grandparents' generation. The initial goal of this study is to recruit 400 schizophrenic probands who meet the following criteria: 1) DSM-IV consensus diagnosis of schizophrenia; 2) two or more psychiatric hospitalizations; 3) ancestry from central valley of Costa Rica; and 4) age of onset prior to age 40. The investigators' hope is to collect information on several subtypes of schizophrenia, such as paranoid, undifferentiated and schizoaffective types. DNA samples will be collected from probands and parents, to allow for haplotype and linkage disequilibrium analyses. In the fifth year, a complete genome screen will be performed at 5 cM intervals, and ancestral haplotype recombination statistics will be used to map schizophrenic predisposition loci. Fine mapping at 1 cM density will be performed across schizophrenic candidate regions identified in this or other populations.
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| Segura-Wang, Maia; Raventos, Henriette; Escamilla, Michael et al. (2010) Assessment of genetic ancestry and population substructure in Costa Rica by analysis of individuals with a familial history of mental disorder. Ann Hum Genet 74:516-24 |
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| Chavarria-Siles, I; Walss-Bass, C; Quezada, P et al. (2007) TGFB-induced factor (TGIF): a candidate gene for psychosis on chromosome 18p. Mol Psychiatry 12:1033-41 |
| Lee, Byung Dae; Walss-Bass, Consuelo; Thompson, Peter M et al. (2007) Malic enzyme 2 and susceptibility to psychosis and mania. Psychiatry Res 150:1-11 |
| Walss-Bass, Consuelo; Montero, Ana Patricia; Armas, Regina et al. (2006) Linkage disequilibrium analyses in the Costa Rican population suggests discrete gene loci for schizophrenia at 8p23.1 and 8q13.3. Psychiatr Genet 16:159-68 |
| Walss-Bass, C; Raventos, H; Montero, A P et al. (2006) Association analyses of the neuregulin 1 gene with schizophrenia and manic psychosis in a Hispanic population. Acta Psychiatr Scand 113:314-21 |
| Walss-Bass, Consuelo; Liu, Wei; Lew, Debbie F et al. (2006) A novel missense mutation in the transmembrane domain of neuregulin 1 is associated with schizophrenia. Biol Psychiatry 60:548-53 |
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