Linkage studies using multiplex families have repeatedly implicated chromosome 8 as involved in schizophrenia etiology. The reported areas of linkage, however, span a wide chromosomal region. The present study used the founder population of the Central Valley of Costa Rica and phenotyping strategies alternative to DSM-IV classifications in attempts to further delimitate the areas on chromosome 8 that may harbor schizophrenia susceptibility genes. A linkage disequilibrium screen of chromosome 8 was performed using family trios of individuals with a history of psychosis. Four discrete regions showing evidence of association (nominal P values less than 0.05) to the phenotype of schizophrenia were identified: 8p23.1, 8p21.3, 8q13.3 and 8q24.3. The region of 8p23.1 precisely overlaps a region showing strong evidence of linkage disequilibrium for severe bipolar disorder in Costa Rica. The same chromosomal regions were identified when the broader phenotype definition of all individuals with functional psychosis was used for analyses. Stratification of the psychotic sample by history of mania suggests that the 8q13.3 locus may be preferentially associated with non-manic psychosis. These results may be helpful in targeting specific areas to be analyzed in association-based or linkage disequilibrium-based studies, for researchers who have found evidence of linkage to schizophrenia on chromosome 8 within their previous studies.
Departments of aPsychiatry
bCellular and Structrual Biology, University of Texas Health Science Center at San Antonio
cSouthwest Foundation for Biomedical Research, San Antonio, Texas
dCenter for research in Cellular and Molecular Biology, University of Costa Rica, San Jose, Costa Rica
eLangley Porter Psychiatric Institute, University of California at San Francisco, San Francisco, California
fDepartment of Psychiatry, Stanford University, Stanford, California, USA
Correspondence and requests for reprints to Michael Escamilla, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
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Sponsorship: This work was supported in part by National Institute of Health Grants R01-MH61884 and K01 MH01453 (M.A.E.), the NARSAD Young Investigator Award (M.A.E.), the Howard Hughes Medical Foundation, the Friends of Psychiatry (UTHSCSA Department of Psychiatry), the International Center for Genetic Engineering and Biotechnology Project CRP/COS98-01 (H.R.), and a National Institute of Health Minority Supplement Award 3 R01-Mh61884 to C.W.B.