Identification of shared risk loci and pathways for bipolar disorder and schizophrenia

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 par
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.
show moreshow less

Metadaten
Author:Andreas Josef Forstner, Julian Hecker, Andrea Hofmann, Anna Maaser, Céline S. Reinbold, Thomas W. Mühleisen, Markus Leber, Jana Strohmaier, Franziska Degenhardt, Jens Treutlein, Manuel Mattheisen, Johannes Schumacher, Fabian Streit, Sandra Meier, Stefan Herms, Per Hoffmann, André Lacour, Stephanie Witt, Andreas Reif, Bertram Müller-Myhsok, Susanne Lucae, Wolfgang Maier, Markus Schwarz, Helmut Vedder, Jutta Kammerer-Ciernioch, Andrea Pfennig, Michael Bauer, Martin Hautzinger, Susanne Moebus, Lorena M. Schenk, Sascha B. Fischer, Sugirthan Sivalingam, Piotr M. Czerski, Joanna Hauser, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Paul E. Brennan, James D. McKay, Adam Wright, Philip B. Mitchell, Janice M. Fullerton, Peter R. Schofield, Grant W. Montgomery, Sarah E. Medland, Scott D. Gordon, Nicholas Gordon Martin, Valery Krasnov, Alexander Chuchalin, Gulja Babadjanova, Galina Pantelejeva, Lilia I. Abramova, Alexander S. Tiganov, Alexey Polonikov, Elza Khusnutdinova, Martin Alda, Cristiana Cruceanu, Guy A. Rouleau, Gustavo Turecki, Catherine Laprise, Fabio Rivas, Fermin Mayoral, Manolis Kogevinas, Maria Șerbanescu-Grigoroiu, Tim Becker, Thomas G. Schulze, Marcella Rietschel, Sven Cichon, Heide Fier, Markus Maria Nöthen
URN:urn:nbn:de:hebis:30:3-428927
URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293228
DOI:http://dx.doi.org/10.1371/journal.pone.0171595
ISSN:1932-6203
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28166306
Parent Title (English):PLoS one
Publisher:PLoS
Place of publication:Lawrence, Kan.
Contributor(s):Consuelo Walss-Bass
Document Type:Article
Language:English
Date of Publication (online):2017/02/23
Date of first Publication:2017/02/06
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/02/23
Volume:12
Issue:(2): e0171595
Pagenumber:14
First Page:1
Last Page:14
Note:
Copyright: © 2017 Forstner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS PPN:448152991
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

$Rev: 11761 $