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000137464 1001_ $$0P:(DE-HGF)0$$aJuraeva, Dilafruz$$b0$$eCorresponding author
000137464 245__ $$aIntegrated pathway-based approach identifies association between genomic regions at CTCF and CACNB2 and schizophrenia.
000137464 260__ $$aSan Francisco, Calif.$$bPublic Library of Science$$c2014
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000137464 520__ $$aIn the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional consequences of such single-nucleotide polymorphisms (SNPs) in the affected genes or their regulatory regions. The Global Test was applied to detect schizophrenia-associated pathways using discovery and replication datasets comprising 5,040 and 5,082 individuals of European ancestry, respectively. Information concerning functional gene-sets was retrieved from the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and the Molecular Signatures Database. Fourteen of the gene-sets or pathways identified in the discovery dataset were confirmed in the replication dataset. These include functional processes involved in transcriptional regulation and gene expression, synapse organization, cell adhesion, and apoptosis. For two genes, i.e. CTCF and CACNB2, evidence for association with schizophrenia was available (at the gene-level) in both the discovery study and published data from the Psychiatric Genomics Consortium schizophrenia study. Furthermore, these genes mapped to four of the 14 presently identified pathways. Several of the SNPs assigned to CTCF and CACNB2 have potential functional consequences, and a gene in close proximity to CACNB2, i.e. ARL5B, was identified as a potential gene of interest. Application of the present hierarchical approach thus allowed: (1) identification of novel biological gene-sets or pathways with potential involvement in the etiology of schizophrenia, as well as replication of these findings in an independent cohort; (2) detection of genes of interest for future follow-up studies; and (3) the highlighting of novel genes in previously reported candidate regions for schizophrenia.
000137464 536__ $$0G:(DE-HGF)POF3-345$$a345 - Population Studies and Genetics (POF3-345)$$cPOF3-345$$fPOF III$$x0
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000137464 650_7 $$2NLM Chemicals$$aCACNB2 protein, human
000137464 650_7 $$2NLM Chemicals$$aCCCTC-Binding Factor
000137464 650_7 $$2NLM Chemicals$$aCTCF protein, human
000137464 650_7 $$2NLM Chemicals$$aCalcium Channels, L-Type
000137464 650_7 $$2NLM Chemicals$$aChromatin
000137464 650_7 $$2NLM Chemicals$$aMembrane Transport Proteins
000137464 650_7 $$2NLM Chemicals$$aRepressor Proteins
000137464 650_7 $$0EC 3.6.1.2$$2NLM Chemicals$$aARL5B protein, human
000137464 650_7 $$0EC 3.6.5.2$$2NLM Chemicals$$aADP-Ribosylation Factors
000137464 650_2 $$2MeSH$$aADP-Ribosylation Factors: genetics
000137464 650_2 $$2MeSH$$aCCCTC-Binding Factor
000137464 650_2 $$2MeSH$$aCalcium Channels, L-Type: genetics
000137464 650_2 $$2MeSH$$aCalcium Signaling: genetics
000137464 650_2 $$2MeSH$$aChromatin: metabolism
000137464 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000137464 650_2 $$2MeSH$$aGenome-Wide Association Study
000137464 650_2 $$2MeSH$$aHumans
000137464 650_2 $$2MeSH$$aLinkage Disequilibrium
000137464 650_2 $$2MeSH$$aMembrane Transport Proteins: genetics
000137464 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000137464 650_2 $$2MeSH$$aRepressor Proteins: genetics
000137464 650_2 $$2MeSH$$aSchizophrenia: genetics
000137464 650_2 $$2MeSH$$aSchizophrenia: metabolism
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