Linkage disequilibrium (LD) analysis has been shown to be an ideal method for mapping complex disease genes in isolated founder populations. This application 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. Our 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 goal of this next phase of the study is to recruit additional 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. Our hope is to collect information on several subtypes of schizophrenia, such as paranoid, undifferentiated and schizoaffective types. DMA samples will be collected from probands and parents, to allow for dense genome wide association analysis. Additional genomic analyses will be performed across schizophrenic candidate regions identified in this or other populations. Relevance to public health: Schizophrenia is a severe, disabling psychiatric condition which affects approximately 2.5 million Americans. Schizophrenia is a brain disorder, and this illness is thought to be inherited. This grant aims to identify the genes which contribute to causing schizophrenia. By identifying the genes which contribute to the diagnosis of schizophrenia, scientists will be able to better diagnose and treat this disabling illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH061884-10
Application #
7886844
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Senthil, Geetha
Project Start
2000-08-01
Project End
2014-04-30
Budget Start
2011-05-15
Budget End
2014-04-30
Support Year
10
Fiscal Year
2011
Total Cost
$481,003
Indirect Cost
Name
Texas Tech University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
609980727
City
Lubbock
State
TX
Country
United States
Zip Code
79430
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Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) Genome-wide association study identifies five new schizophrenia loci. Nat Genet 43:969-76
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
Walss-Bass, Consuelo; Soto-Bernardini, Maria Clara; Johnson-Pais, Teresa et al. (2009) Methionine sulfoxide reductase: a novel schizophrenia candidate gene. Am J Med Genet B Neuropsychiatr Genet 150B:219-25
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
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
Campos-Sanchez, Rebeca; Barrantes, Ramiro; Silva, Sandra et al. (2006) Genetic structure analysis of three Hispanic populations from Costa Rica, Mexico, and the southwestern United States using Y-chromosome STR markers and mtDNA sequences. Hum Biol 78:551-63
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

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