title: Diverse types of genetic variation converge on functional gene networks involved in schizophrenia.
abstract: 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.affiliation: Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Gilman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Tejdeep S
authors.initials: TS
authors.lastname: Bawa
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gogos
authors.forename: Maria
authors.initials: M
authors.lastname: Karayiorgou
authors.forename: Dennis
authors.initials: D
authors.lastname: Vitkup
mesh_terms: D001321:Autistic Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D016000:Cluster Analysis; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005810:Multigene Family / Q000235:genetics*; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*