Document Detail


Diverse types of genetic variation converge on functional gene networks involved in schizophrenia.
MedLine Citation:
PMID:  23143521     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Despite the successful identification of several relevant genomic loci, the underlying molecular mechanisms of schizophrenia remain largely unclear. We developed a computational approach (NETBAG+) that allows an integrated analysis of diverse disease-related genetic data using a unified statistical framework. The application of this approach to schizophrenia-associated genetic variations, obtained using unbiased whole-genome methods, allowed us to identify several cohesive gene networks related to axon guidance, neuronal cell mobility, synaptic function and chromosomal remodeling. The genes forming the networks are highly expressed in the brain, with higher brain expression during prenatal development. The identified networks are functionally related to genes previously implicated in schizophrenia, autism and intellectual disability. A comparative analysis of copy number variants associated with autism and schizophrenia suggests that although the molecular networks implicated in these distinct disorders may be related, the mutations associated with each disease are likely to lead, at least on average, to different functional consequences.
Authors:
Sarah R Gilman; Jonathan Chang; Bin Xu; Tejdeep S Bawa; Joseph A Gogos; Maria Karayiorgou; Dennis Vitkup
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-11
Journal Detail:
Title:  Nature neuroscience     Volume:  15     ISSN:  1546-1726     ISO Abbreviation:  Nat. Neurosci.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-28     Completed Date:  2013-01-29     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  9809671     Medline TA:  Nat Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1723-8     Citation Subset:  IM    
Affiliation:
Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Autistic Disorder / diagnosis,  epidemiology,  genetics
Cluster Analysis
Gene Expression Regulation, Developmental
Gene Regulatory Networks / genetics*
Genetic Predisposition to Disease / epidemiology,  genetics
Genetic Variation / genetics*
Genome-Wide Association Study
Humans
Intellectual Disability / diagnosis,  epidemiology,  genetics
Multigene Family / genetics*
Phenotype*
Protein Interaction Domains and Motifs / genetics
Schizophrenia / diagnosis,  epidemiology,  genetics*
Grant Support
ID/Acronym/Agency:
MH061399/MH/NIMH NIH HHS; MH077235/MH/NIMH NIH HHS; R01 GM079759/GM/NIGMS NIH HHS; T32 GM082797/GM/NIGMS NIH HHS; T32 GM082797/GM/NIGMS NIH HHS; U54 CA121852/CA/NCI NIH HHS; U54CA121852/CA/NCI NIH HHS
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