Schizophrenia is a common, disabling disorder with a lifetime morbid risk of 1%. Its etiology is unknown, but a relatively high heritability (60-70%) is well established. Prior gene mapping efforts have achieved limited success, probably due to the complex genetic etiology. We propose to build on the strengths of linkage analyses and available information about pathogenesis to detect gene/s conferring liability. Specifically, targeting genomic regions identified by linkage analysis and guided by data suggesting dopaminergic (DA) dysregulation in the brains of patients with schizophrenia, we will test positional candidate genes involved in DA neurotransmission. Such a strategy also garners support from family-based association analyses, as we and others have also detected plausible linkage and association with DA genes. To identify liability genes, we will use the results of an in-progress genome scan using 400 affected sib-pairs (ASPs). We will choose approximately 20 positional candidates based on the intersection of information from the genome scan and the neuroscience of DA. These genes will be evaluated through multi-layered analyses involving linkage and linkage I association among a total of 680 ASPs and 930 simplex case-parent trio families. We will utilize selected, informative single nucleotide polymorphisms (SNPs) and haplotypes. Initial results from a US/UK sample will be evaluated in an independent Asian Indian sample. Genes surviving this intense interrogation will be assessed further by functional assays and the available information synthesized. Clinical information and DNA from consenting US participants will be available to the scientific community. This is a competing renewal of grant # MH 56242

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH056242-10
Application #
7113185
Study Section
Genome Study Section (GNM)
Program Officer
Lehner, Thomas
Project Start
1997-06-01
Project End
2009-07-31
Budget Start
2006-08-01
Budget End
2009-07-31
Support Year
10
Fiscal Year
2006
Total Cost
$481,608
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Bhatia, Triptish; Wood, Joel; Iyengar, Satish et al. (2018) Emotion discrimination in humans: Its association with HSV-1 infection and its improvement with antiviral treatment. Schizophr Res 193:161-167
D'Aiuto, Leonardo; Williamson, Kelly; Dimitrion, Peter et al. (2017) Comparison of three cell-based drug screening platforms for HSV-1 infection. Antiviral Res 142:136-140
Nimgaonkar, V L; Prasad, K M; Chowdari, K V et al. (2017) The complement system: a gateway to gene-environment interactions in schizophrenia pathogenesis. Mol Psychiatry 22:1554-1561
Bhatia, Triptish; Gettig, Elizabeth A; Gottesman, Irving I et al. (2016) Stratifying empiric risk of schizophrenia among first degree relatives using multiple predictors in two independent Indian samples. Asian J Psychiatr 24:79-84
De, Sreeja; Bhatia, Triptish; Thomas, Pramod et al. (2013) Bizarre delusions: a qualitative study on Indian schizophrenia patients. Indian J Psychol Med 35:268-72
Talati, Ardesheer; Wickramaratne, Priya J; Keyes, Katherine M et al. (2013) Smoking and psychopathology increasingly associated in recent birth cohorts. Drug Alcohol Depend 133:724-32
Kukshal, Prachi; Kodavali, Venkat Chowdari; Srivastava, Vibhuti et al. (2013) Dopaminergic gene polymorphisms and cognitive function in a north Indian schizophrenia cohort. J Psychiatr Res 47:1615-22
Odgerel, Z; Talati, A; Hamilton, S P et al. (2013) Genotyping serotonin transporter polymorphisms 5-HTTLPR and rs25531 in European- and African-American subjects from the National Institute of Mental Health's Collaborative Center for Genomic Studies. Transl Psychiatry 3:e307
Bhatia, Triptish; Agarwal, Akhilesh; Shah, Gyandeepak et al. (2012) Adjunctive cognitive remediation for schizophrenia using yoga: an open, non-randomized trial. Acta Neuropsychiatr 24:91-100
Bhatia, Triptish; Agarwal, Akhilesh; Shah, Gyandeepak et al. (2012) Adjunctive cognitive remediation for schizophrenia using yoga: an open, non-randomised trial. Acta Neuropsychiatr 24:91-100

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