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Identifying the genetic cis associations between DNA variants (single-nucleotide polymorphisms (SNPs)) and gene expression in brain tissue may be a promising approach to find functionally relevant pathways that contribute to the etiology of psychiatric disorders. In this study, we examined the association between genetic variations and gene expression in prefrontal cortex, hippocampus, temporal cortex, thalamus and cerebellum in subjects with psychiatric disorders and in normal controls. We identified cis associations between 648 transcripts and 6725 SNPs in the various brain regions. Several SNPs showed brain regional-specific associations. The expression level of only one gene, PDE4DIP, was associated with a SNP, rs12124527, in all the brain regions tested here. From our data, we generated a list of brain cis expression quantitative trait loci (eQTL) genes that we compared with a list of schizophrenia candidate genes downloaded from the Schizophrenia Forum (SZgene) database (http://www.szgene.org/). Of the SZgene candidate genes, we found that the expression levels of four genes, HTR2A, PLXNA2, SRR and TCF4, were significantly associated with cis SNPs in at least one brain region tested. One gene, SRR, was also involved in a coexpression module that we found to be associated with disease status. In addition, a substantial number of cis eQTL genes were also involved in the module, suggesting eQTL analysis of brain tissue may identify more reliable susceptibility genes for schizophrenia than case-control genetic association analyses. In an attempt to facilitate the identification of genetic variations that may underlie the etiology of major psychiatric disorders, we have integrated the brain eQTL results into a public and online database, Stanley Neuropathology Consortium Integrative Database (SNCID; http://sncid.stanleyresearch.org).
Pubmed ID: 22832957 RIS Download
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Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsA database of 1749 neuropathological markers measured in 12 different brain regions from 60 brains in the Consortium Collection from the Stanley Medical Research Institute combined with microarray data and statistical tools. Fifteen brains each are from patients diagnosed with schizophrenia, bipolar disorder, or major depression, and unaffected controls. The four groups are matched by age, sex, race, postmortem interval, pH, side of brain, and mRNA quality. A Repository of raw data is also included. Users must register for access.
View all literature mentionsComputable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsThe SZGene database provides a comprehensive, unbiased and regularly updated field synopsis of genetic association studies performed in schizophrenia. In addition, hundreds of up-to-date meta-analyses are available for all eligible polymorphisms with sufficient data. Eligible publications are identified following systematic searches of scientific literature databases, as well as the table of contents of journals in genetics and psychiatry. The database can be searched either by a variety of dropdown menus or by specific keywords. For each gene, summary overviews are provided displaying key characteristics for each publication, including links to genotype distributions of the polymorphisms studied, random-effects allelic meta-analyses, and funnel plots for an assessment of publication bias.
View all literature mentionsAn integrated software package for the visualization and statistical analysis of DNA microarray gene expression data.
View all literature mentionsOpen source whole genome association analysis toolset, designed to perform range of basic, large scale analyses in computationally efficient manner. Used for analysis of genotype/phenotype data. Through integration with gPLINK and Haploview, there is some support for subsequent visualization, annotation and storage of results. PLINK 1.9 is improved and second generation of the software.
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