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Title: Identification of shared risk loci and pathways for bipolar disorder and schizophrenia.
Authors: Forstner, Andreas J
Hecker, Julian
Hofmann, Andrea
Maaser, Anna
Reinbold, Céline S
Mühleisen, Thomas W
Leber, Markus
Strohmaier, Jana
Degenhardt, Franziska
Treutlein, Jens
Mattheisen, Manuel
Schumacher, Johannes
Streit, Fabian
Meier, Sandra
Herms, Stefan
Hoffmann, Per
Lacour, André
Witt, Stephanie H
Reif, Andreas
Müller-Myhsok, Bertram
Lucae, Susanne
Maier, Wolfgang
Schwarz, Markus
Vedder, Helmut
Kammerer-Ciernioch, Jutta
Pfennig, Andrea
Bauer, Michael
Hautzinger, Martin
Moebus, Susanne
Schenk, Lorena M
Fischer, Sascha B
Sivalingam, Sugirthan
Czerski, Piotr M
Hauser, Joanna
Lissowska, Jolanta
Szeszenia-Dabrowska, Neonila
Brennan, Paul
McKay, James D
Wright, Adam
Mitchell, Philip B
Fullerton, Janice M
Schofield, Peter R
Montgomery, Grant W
Medland, Sarah E
Gordon, Scott D
Martin, Nicholas G
Krasnov, Valery
Chuchalin, Alexander
Babadjanova, Gulja
Pantelejeva, Galina
Abramova, Lilia I
Tiganov, Alexander S
Polonikov, Alexey
Khusnutdinova, Elza
Alda, Martin
Cruceanu, Cristiana
Rouleau, Guy A
Turecki, Gustavo
Laprise, Catherine
Rivas, Fabio
Mayoral, Fermin
Kogevinas, Manolis
Grigoroiu-Serbanescu, Maria
Becker, Tim
Schulze, Thomas G
Rietschel, Marcella
Cichon, Sven
Fier, Heide
Nöthen, Markus M
metadata.dc.subject.mesh: Bipolar Disorder
Genetic Linkage
Genetic Predisposition to Disease
Genome-Wide Association Study
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Signal Transduction
Issue Date: 6-Feb-2017
Abstract: Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
metadata.dc.identifier.doi: 10.1371/journal.pone.0171595
Appears in Collections:Producción 2020

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