This is an application for a 4-year continuation of a Collaborative Study of Mental Disorders (CSMD). Sites and PIs include U. Chicago (P. Gejman, coordinator), Baylor (F.Amin), LSU (N. Buccola), UC Irvine (W. Byerley), Washington Univ. (C.R. Cloninger), U. Iowa (R. Crowe), U. Colorado (R. Freedman), U. Pennsylvania (D. Levinson), U. Queensland (B. Mowry), and Mt. Sinai (J. Silverman). Currently these sites are collecting 507 schizophrenia (SZ) affected sibling pairs (ASPs) for the NIMH Genetics Initiative repository to add to a previous smaller collection, and will complete a genome scan linkage analysis. It is now proposed to collect a repository sample of 4,500 SZ cases of European and African-American ancestry (plus 1,800 available parents) using the same clinical assessment methods, and 4,500 ethnically-matched controls selected from the general population, and to initiate a set of experiments to clone one or more SZ susceptibility genes using both the ASP and case-control samples in an integrated fashion. Positional candidate regions will be selected based on our genome scan and meta-analysis data for all SZ scans. In these regions, 2 cM maps of microsatellite markers will by typed in the combined Genetics Initiative SZ ASP sample (620 ASPs), and at least one candidate region selected for LD mapping studies. During year 3, a 20 kb map of this region (480 SNPs, = 10 MB) will be genotyped in the ASP sample and the first half of the case-control sample using the Illumina Corp. BeadArray method, and 24 microsatellites selected for maximum African-European allele frequency difference will be typed in all African-American cases and controls and a subset of European-ancestry cases. Genetic analyses will be carried out to assess association of SNP variation with disease, and association of this evidence with support for linkage in ASPs, taking population substructure and admixture into account. In year 4, 96 of these SNPs from the positive regions will be typed in the second half-sample of cases and controls for replication and whole-sample analyses. Finally, genetic diversity and LD structure will be more comprehensively characterized in positional candidate genes identified in associated regions, and 288 SNPs will be typed in the entire case-control sample to test these genes and SZ candidate genes identified in other studies. The goal of the study is to identify one or more SZ susceptibility genes whose subsequent characterization inmolecular and functional studies will elucidate the pathophysiology and treatment of SZ.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH059587-08
Application #
6942289
Study Section
Special Emphasis Panel (ZRG1-MGN (02))
Program Officer
Lehner, Thomas
Project Start
1998-09-30
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
8
Fiscal Year
2005
Total Cost
$481,432
Indirect Cost
Name
Emory University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Kos, Mark Z; Duan, Jubao; Sanders, Alan R et al. (2018) Dopamine perturbation of gene co-expression networks reveals differential response in schizophrenia for translational machinery. Transl Psychiatry 8:278
(2018) Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet 50:668-681
Ho, Kwo Wei David; Han, Shizhong; Nielsen, Jakob V et al. (2018) Genome-wide association study of seasonal affective disorder. Transl Psychiatry 8:190
Duan, Jubao; Göring, Harald H H; Sanders, Alan R et al. (2018) Transcriptomic signatures of schizophrenia revealed by dopamine perturbation in an ex vivo model. Transl Psychiatry 8:158
Sanders, A R; Drigalenko, E I; Duan, J et al. (2017) Transcriptome sequencing study implicates immune-related genes differentially expressed in schizophrenia: new data and a meta-analysis. Transl Psychiatry 7:e1093
Sanders, Alan R; Beecham, Gary W; Guo, Shengru et al. (2017) Genome-Wide Association Study of Male Sexual Orientation. Sci Rep 7:16950
Liu, C; Bousman, C A; Pantelis, C et al. (2017) Pathway-wide association study identifies five shared pathways associated with schizophrenia in three ancestral distinct populations. Transl Psychiatry 7:e1037
Rees, Elliott; Kendall, Kimberley; Pardiñas, Antonio F et al. (2016) Analysis of Intellectual Disability Copy Number Variants for Association With Schizophrenia. JAMA Psychiatry 73:963-969
Han, Jun; Walters, James T R; Kirov, George et al. (2016) Gender differences in CNV burden do not confound schizophrenia CNV associations. Sci Rep 6:25986
Otowa, T; Hek, K; Lee, M et al. (2016) Meta-analysis of genome-wide association studies of anxiety disorders. Mol Psychiatry 21:1391-9

Showing the most recent 10 out of 130 publications