TY  - JOUR
AU  - Juraeva, Dilafruz
AU  - Hänisch, Britta
AU  - Zapatka, Marc
AU  - Frank, Josef
AU  - Investigators, GROUP
AU  - Group, PSYCH-GEMS SCZ Working
AU  - Witt, Stephanie H
AU  - Mühleisen, Thomas W
AU  - Treutlein, Jens
AU  - Strohmaier, Jana
AU  - Meier, Sandra
AU  - Degenhardt, Franziska
AU  - Giegling, Ina
AU  - Ripke, Stephan
AU  - Leber, Markus
AU  - Lange, Christoph
AU  - Schulze, Thomas G
AU  - Mössner, Rainald
AU  - Nenadic, Igor
AU  - Sauer, Heinrich
AU  - Rujescu, Dan
AU  - Maier, Wolfgang
AU  - Børglum, Anders
AU  - Ophoff, Roel
AU  - Cichon, Sven
AU  - Nöthen, Markus M
AU  - Rietschel, Marcella
AU  - Mattheisen, Manuel
AU  - Brors, Benedikt
AU  - Kahn, René S
AU  - Cahn, Wiepke
AU  - Linszen, Don H
AU  - de Haan, Lieuwe
AU  - van Os, Jim
AU  - Krabbendam, Lydia
AU  - Myin-Germeys, Inez
AU  - Wiersma, Durk
AU  - Bruggeman, Richard
AU  - Mors, O.
AU  - Børglum, A. D.
AU  - Mortensen, P. B.
AU  - Pedersen, C. B.
AU  - Demontis, D.
AU  - Grove, J.
AU  - Mattheisen, M.
AU  - Børglum, A. D.
AU  - Mortensen, P. B.
AU  - Pedersen, C. B.
AU  - Hougaard, D. M.
AU  - Demontis, D.
AU  - Grove, J.
AU  - Mattheisen, M.
AU  - Børglum, A. D.
AU  - Grove, J.
AU  - Mattheisen, M.
AU  - Mattheisen, M.
TI  - Integrated pathway-based approach identifies association between genomic regions at CTCF and CACNB2 and schizophrenia.
JO  - PLoS Genetics
VL  - 10
IS  - 6
SN  - 1553-7404
CY  - San Francisco, Calif.
PB  - Public Library of Science
M1  - DZNE-2020-03786
SP  - e1004345
PY  - 2014
AB  - In 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.
KW  - ADP-Ribosylation Factors: genetics
KW  - CCCTC-Binding Factor
KW  - Calcium Channels, L-Type: genetics
KW  - Calcium Signaling: genetics
KW  - Chromatin: metabolism
KW  - Genetic Predisposition to Disease
KW  - Genome-Wide Association Study
KW  - Humans
KW  - Linkage Disequilibrium
KW  - Membrane Transport Proteins: genetics
KW  - Polymorphism, Single Nucleotide
KW  - Repressor Proteins: genetics
KW  - Schizophrenia: genetics
KW  - Schizophrenia: metabolism
KW  - CACNB2 protein, human (NLM Chemicals)
KW  - CCCTC-Binding Factor (NLM Chemicals)
KW  - CTCF protein, human (NLM Chemicals)
KW  - Calcium Channels, L-Type (NLM Chemicals)
KW  - Chromatin (NLM Chemicals)
KW  - Membrane Transport Proteins (NLM Chemicals)
KW  - Repressor Proteins (NLM Chemicals)
KW  - ARL5B protein, human (NLM Chemicals)
KW  - ADP-Ribosylation Factors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24901509
C2  - pmc:PMC4046913
DO  - DOI:10.1371/journal.pgen.1004345
UR  - https://pub.dzne.de/record/137464
ER  -