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@ARTICLE{Juraeva:137464,
author = {Juraeva, Dilafruz and Hänisch, Britta and Zapatka, Marc
and Frank, Josef and Investigators, GROUP and Group,
PSYCH-GEMS SCZ Working and Witt, Stephanie H and Mühleisen,
Thomas W and Treutlein, Jens and Strohmaier, Jana and Meier,
Sandra and Degenhardt, Franziska and Giegling, Ina and
Ripke, Stephan and Leber, Markus and Lange, Christoph and
Schulze, Thomas G and Mössner, Rainald and Nenadic, Igor
and Sauer, Heinrich and Rujescu, Dan and Maier, Wolfgang and
Børglum, Anders and Ophoff, Roel and Cichon, Sven and
Nöthen, Markus M and Rietschel, Marcella and Mattheisen,
Manuel and Brors, Benedikt and Kahn, René S and Cahn,
Wiepke and Linszen, Don H and de Haan, Lieuwe and van Os,
Jim and Krabbendam, Lydia and Myin-Germeys, Inez and
Wiersma, Durk and Bruggeman, Richard and Mors, O. and
Børglum, A. D. and Mortensen, P. B. and Pedersen, C. B. and
Demontis, D. and Grove, J. and Mattheisen, M. and Børglum,
A. D. and Mortensen, P. B. and Pedersen, C. B. and Hougaard,
D. M. and Demontis, D. and Grove, J. and Mattheisen, M. and
Børglum, A. D. and Grove, J. and Mattheisen, M. and
Mattheisen, M.},
title = {{I}ntegrated pathway-based approach identifies association
between genomic regions at {CTCF} and {CACNB}2 and
schizophrenia.},
journal = {PLoS Genetics},
volume = {10},
number = {6},
issn = {1553-7404},
address = {San Francisco, Calif.},
publisher = {Public Library of Science},
reportid = {DZNE-2020-03786},
pages = {e1004345},
year = {2014},
abstract = {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.},
keywords = {ADP-Ribosylation Factors: genetics / CCCTC-Binding Factor /
Calcium Channels, L-Type: genetics / Calcium Signaling:
genetics / Chromatin: metabolism / Genetic Predisposition to
Disease / Genome-Wide Association Study / Humans / Linkage
Disequilibrium / Membrane Transport Proteins: genetics /
Polymorphism, Single Nucleotide / Repressor Proteins:
genetics / Schizophrenia: genetics / Schizophrenia:
metabolism / CACNB2 protein, human (NLM Chemicals) /
CCCTC-Binding Factor (NLM Chemicals) / CTCF protein, human
(NLM Chemicals) / Calcium Channels, L-Type (NLM Chemicals) /
Chromatin (NLM Chemicals) / Membrane Transport Proteins (NLM
Chemicals) / Repressor Proteins (NLM Chemicals) / ARL5B
protein, human (NLM Chemicals) / ADP-Ribosylation Factors
(NLM Chemicals)},
cin = {U T4 Researchers - Bonn / AG Hänisch},
ddc = {610},
cid = {I:(DE-2719)7000008 / I:(DE-2719)1013010},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24901509},
pmc = {pmc:PMC4046913},
doi = {10.1371/journal.pgen.1004345},
url = {https://pub.dzne.de/record/137464},
}