This revised application for an Independent Scientist Award (K02) is focused on the genetic epidemiology of schizophrenia. Identified genetic factors of etiological importance will be examined in conjunction with non-genetic risk factors for schizophrenia Initially, it is proposed to test-I association of schizophrenia with the HLA DQB1 locus using family based studies. This locus was identified by the applicant in four independent case control studies and lies within the region of interest on chromosome 6p identified by other groups. Interactions between this putative susceptibility gene and other environmental risk factors will then be examined. Next, the role of selected 'candidate' genes will be investigated, followed by a genome wide scan to identify other regions of susceptibility. 1. Replicative studies of the original association at the HLA DQB1 locus using family based studies. 2. Refinement of the association using genetic markers flanking the HLA DQB1 locus and examination of possible associations at the sub-syndromal level. 3. Analysis of risk conferred by alleles of the HLA DQBI gene (or a linked gene with stronger association) in conjunction with known risk factors, including putative viral etiological agents. 4. Identification of other susceptibility genes and investigation of gene-environment interactions using the paradigm for the HLA DQB 1 locus. Using a training award from NIMH, the applicant initiated ascertainment of samples locally and internationally for association and linkage studies. The samples will be enlarged. The applicant has received training in basic molecular genetic and statistical techniques. The present proposal will be used as a vehicle for further training in related areas. The specific etiology of schizophrenia, a common, devastating illness is unknown. Since a significant genetic predisposition is well established, identification of predisposing genetic factors is feasible. Such information, in conjunction with non-genetic risk factors may help identify individuals at increased risk and thus enable prevention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
1K02MH001489-01A1
Application #
2465847
Study Section
Epidemiology and Genetics Review Committee (EPI)
Program Officer
Moldin, Steven Owen
Project Start
1998-03-10
Project End
2003-02-28
Budget Start
1998-03-10
Budget End
1999-02-28
Support Year
1
Fiscal Year
1998
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
Shirts, Brian H; Prasad, Konasale M; Pogue-Geile, Michael F et al. (2008) Antibodies to cytomegalovirus and Herpes Simplex Virus 1 associated with cognitive function in schizophrenia. Schizophr Res 106:268-74
Thomas, Pramod; Srivastava, Vibhuti; Singh, Anuradha et al. (2008) Correlates of response to Olanzapine in a North Indian Schizophrenia sample. Psychiatry Res 161:275-83
Thomas, P; Mathur, P; Gottesman, I I et al. (2007) Correlates of hallucinations in schizophrenia: A cross-cultural evaluation. Schizophr Res 92:41-9
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
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
Bacanu, Silviu-Alin; Devlin, Bernie; Chowdari, Kodavali V et al. (2005) Heritability of psychosis in Alzheimer disease. Am J Geriatr Psychiatry 13:624-7
Prasad, K M R; Chowdari, K V; Nimgaonkar, V L et al. (2005) Genetic polymorphisms of the RGS4 and dorsolateral prefrontal cortex morphometry among first episode schizophrenia patients. Mol Psychiatry 10:213-9
Lee, Yu-Sang; Miller, Mary; Hassett, Andrea Cortese et al. (2004) von Willebrand's disease and psychotic disorders: co-segregation and genetic associations. Bipolar Disord 6:150-5
Prasad, S; Chowdari, K V; Wood, J et al. (2004) Association analysis of NOTCH 4 polymorphisms with schizophrenia among two independent family based samples. Am J Med Genet B Neuropsychiatr Genet 131B:6-9

Showing the most recent 10 out of 28 publications