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000154143 0247_ $$2doi$$a10.1371/journal.pgen.1004345
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000154143 037__ $$aFZJ-2014-03536
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000154143 1001_ $$0P:(DE-HGF)0$$aHolmans, Peter$$b0$$eCorresponding Author
000154143 245__ $$aIntegrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia
000154143 260__ $$aSan Francisco, Calif.$$bPublic Library of Science$$c2014
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000154143 520__ $$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.
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000154143 7001_ $$0P:(DE-HGF)0$$aHaenisch, Britta$$b1
000154143 7001_ $$0P:(DE-HGF)0$$aZapatka, Marc$$b2
000154143 7001_ $$0P:(DE-HGF)0$$aFrank, Josef$$b3
000154143 7001_ $$0P:(DE-HGF)0$$aWitt, Stephanie H.$$b4
000154143 7001_ $$0P:(DE-Juel1)156419$$aMühleisen, Thomas$$b5$$ufzj
000154143 7001_ $$0P:(DE-HGF)0$$aTreutlein, Jens$$b6
000154143 7001_ $$0P:(DE-HGF)0$$aStrohmaier, Jana$$b7
000154143 7001_ $$0P:(DE-HGF)0$$aMeier, Sandra$$b8
000154143 7001_ $$0P:(DE-HGF)0$$aDegenhardt, Franziska$$b9
000154143 7001_ $$0P:(DE-HGF)0$$aGiegling, Ina$$b10
000154143 7001_ $$0P:(DE-HGF)0$$aRipke, Stephan$$b11
000154143 7001_ $$0P:(DE-HGF)0$$aLeber, Markus$$b12
000154143 7001_ $$0P:(DE-HGF)0$$aLange, Christoph$$b13
000154143 7001_ $$0P:(DE-HGF)0$$aSchulze, Thomas G.$$b14
000154143 7001_ $$0P:(DE-HGF)0$$aMössner, Rainald$$b15
000154143 7001_ $$0P:(DE-HGF)0$$aNenadic, Igor$$b16
000154143 7001_ $$0P:(DE-HGF)0$$aSauer, Heinrich$$b17
000154143 7001_ $$0P:(DE-HGF)0$$aRujescu, Dan$$b18
000154143 7001_ $$0P:(DE-HGF)0$$aMaier, Wolfgang$$b19
000154143 7001_ $$0P:(DE-HGF)0$$aBørglum, Anders$$b20
000154143 7001_ $$0P:(DE-HGF)0$$aOphoff, Roel$$b21
000154143 7001_ $$0P:(DE-Juel1)140234$$aCichon, Sven$$b22$$ufzj
000154143 7001_ $$0P:(DE-HGF)0$$aNöthen, Markus M.$$b23
000154143 7001_ $$0P:(DE-HGF)0$$aRietschel, Marcella$$b24
000154143 7001_ $$0P:(DE-HGF)0$$aMattheisen, Manuel$$b25
000154143 7001_ $$0P:(DE-HGF)0$$aBrors, Benedikt$$b26
000154143 7001_ $$0P:(DE-HGF)0$$aHolmans, Peter$$b27
000154143 773__ $$0PERI:(DE-600)2186725-2$$a10.1371/journal.pgen.1004345$$gVol. 10, no. 6, p. e1004345 -$$n6$$pe1004345$$tPLoS Genetics$$v10$$x1553-7404$$y2014
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