This application for a FIRST award is focused on the genetic epidemiology of schizophrenia. Though a genetic etiology for schizophrenia is accepted, the mode of inheritance and the nature of the disease gene/s are unknown. In order to identify such genes without assuming the mode of inheritance a case-control association study is proposed. The study will investigate proposed associations with schizophrenia at two loci: (i) a positive association at the dopamine D3 receptor gene (D3RG) locus, (ii) a negative association at the HLA DQB1 gene locus. These hypotheses are based on the applicant's preliminary studies, which suggest associations among individuals of African-American ethnicity. Therefore, the probands will be African-Americans with a diagnosis of schizophrenia (DSM IIlR criteria, n= 150). The distribution of alleles of D3RG and HLA DQB 1 among the probands will be compared with two groups of controls: (i) a hypothetical group composed of alleles not transmitted to each proband by his/her parents (the haplotype relative risk method); (ii) cord blood samples from African-American neonates born locally. Molecular genetic analysis will be conducted using published methods. If the preliminary associations are not detected, associations at other 'candidate gene' loci will be investigated. Though the probands will be ascertained using DSM IIIR criteria, associations based on other diagnostic schemes will also be tested. Thus, biologically meaningful associations may be detected. This will help identify disease susceptibility genes, which will be useful for identifying individuals at risk. This study is among the first of its kind among African- Americans - a hitherto neglected area of research. The applicant has received a Scientist Development Award for Clinicians (K20MH00966, Sept. '92 -Aug. '97, ADAMHA). He has obtained clinical and laboratory based training in genetic epidemiology. He is currently conducting genetic studies in schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH053459-05
Application #
2890646
Study Section
Epidemiology and Genetics Review Committee (EPI)
Program Officer
Moldin, Steven Owen
Project Start
1995-09-30
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2001-04-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Shirts, Brian H; Kim, Jung Jin; Reich, Shani et al. (2007) Polymorphisms in MICB are associated with human herpes virus seropositivity and schizophrenia risk. Schizophr Res 94:342-53
Kim, Jung Jin; Shirts, Brian H; Dayal, Madhulika et al. (2007) Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia? Ann Med 39:145-53
Talkowski, Michael E; Seltman, Howard; Bassett, Anne S et al. (2006) Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples. Biol Psychiatry 60:152-62
Talkowski, Michael E; Mansour, Hader; Chowdari, Kodavali V et al. (2006) Novel, replicated associations between dopamine D3 receptor gene polymorphisms and schizophrenia in two independent samples. Biol Psychiatry 60:570-7
Shirts, Brian H; Bamne, Mikhil; Kim, Jung Jin et al. (2006) A comprehensive genetic association and functional study of TNF in schizophrenia risk. Schizophr Res 83:7-13
Talkowski, Michael E; Chowdari, Kv; Lewis, David A et al. (2006) Can RGS4 polymorphisms be viewed as credible risk factors for schizophrenia? A critical review of the evidence. Schizophr Bull 32:203-8

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