Text Size
A A A
U. S. Department of Health and Human Services
Skip Navigation

Home > RePORTER > Project Information

Project InformationProject Information Help

Project Number: 5U01MH079470-03    Former Number: 1R01MH079470-01A1 Contact PI / Project Leader: LEVINSON, DOUGLAS FREDERICK
Title: GENOME-WIDE ASSOCIATION STUDY OF SCHIZOPHRENIA Awardee Organization: STANFORD UNIVERSITY
Description
Abstract Text:
DESCRIPTION (provided by applicant): This is a revised application for 3 years of funding for two sites and 5 consortium sites (PA 05-106, "Deep Sequencing and Haplotype Profiling of Mental Disorders"). The goal is to identify and characterize genetic variation that contributes to schizophrenia (SZ) susceptibility, by carrying out a genome-wide association GWA) study followed by resequencing, genotyping and biological experiments. Two samples will be studied: 3,000 SZ and 3,000 control subjects of European ancestry (EA), and 1,200 cases and 1,200 controls of African-American (AA) ancestry. The GWA datasets will include 550,000 SNPs in the EA sample (the revised Affymetrix 500K array and 50K Gene-Focused chip that includes 20K nsSNPs), and the new Affymetrix 1M array in the AA sample (the 500K array and 500K additional SNPs with increased coverage of African variation). The new 500K array also provides genomewide assays of additional copy number variants (CNVs). The Genetic Association Information Network (GAIN) will genotype 1450/1450 EA cases/controls (500K) and the entire AA sample (1M). The Affymetrix consortium site will genotype the remaining 1550/1550 EA cases/controls with the 500K array, and all EA subjects with the 50K chip. Preliminary statistical studies are proposed, to select an optimal data analysis strategy that tests every HapMap SNP using single- and multi-marker tests, evaluates evidence for association on European- and African-ancestry chromosomes (after inferring local ancestry in admixed individuals) and in the combined data, controls for subtle population substructure, and evaluates empirical p-values through permutation. A set of" 15 candidate intervals will be selected based on p-value threshold, Rank Truncated Product analysis, replication experiments, and bioinformatic and biological information. Deep resequencing experiments will detect any significant case-control difference in rare functional mutations, and will discover new rare and common SNPs. Further genotyping of each region will include rare/functional SNPs and additional common SNPs for optimal tagging of common variants. Based on evidence for association and available information about each gene, the associated genomic interval, and the associated variants, biological studies will be undertaken to begin to evaluate the functional effects of these variants and the implications for hypothesis about mechanisms underlying susceptibility to SZ.
NIH Spending Category:
Brain Disorders; Clinical Research; Genetics; Human Genome; Mental Health; Schizophrenia
Project Terms:
African; African American; base; Bioinformatics; Biological; Biological Assay; Brain; Candidate Disease Gene; case control; Chromosomes; Clinical; Clinical Data; Code; Complex; Conserved Sequence; cost; Data; Data Analyses; Data Set; Databases; Development; Disease; DNA Resequencing; Elements; European; Exons; Family; Frequencies (time pattern); Functional disorder; Funding; Gene Expression; gene interaction; Genes; genetic association; genome wide association study; genome-wide; Genomics; Genotype; Goals; Grant; Haplotypes; improved; Individual; Information Networks; Maps; Mental disorders; Methodological Studies; Methods; Morbidity - disease rate; Mutation; NIH Program Announcements; Online Systems; Pathway interactions; Policies; Population; positional cloning; Predisposition; programs; Reporting; repository; Research Design; Research Personnel; research study; Risk; Role; Sampling; Schizophrenia; sharing data; Site; Statistical Methods; Statistical Study; Testing; Update; Variant; Variation (Genetics)



The RePORTER database is available to all public users at http://exporter.nih.gov/. As the data are available for bulk download, the RePORTER system reserves the right to block IP addresses that fail to adhere to instructions in the system’s robots.txt files or submit requests at a rate that negatively impacts service delivery to other users. RePORTER reserves the right to terminate any automated query to the RePORTER application that negatively affects service delivery to other users.

Page Last Updated on February 17, 2013
This site is best viewed with Internet Explorer (7.0 or higher) or Mozilla Firefox (3.0).

NIH...Turning Discovery Into Health®
RePORTER2