Forstner, Andreas J., Hecker, Julian, Hofmann, Andrea, Maaser, Anna, Reinbold, Celine S., Muehleisen, Thomas W., Leber, Markus, Strohmaier, Jana, Degenhardt, Franziska, Treutlein, Jens, Mattheisen, Manuel ORCID: 0000-0002-8442-493X, Schumacher, Johannes, Streit, Fabian ORCID: 0000-0003-1080-4339, Meier, Sandra, Herms, Stefan ORCID: 0000-0002-2786-8200, Hoffmann, Per, Lacour, Andre ORCID: 0000-0003-2692-2583, Witt, Stephanie H., Reif, Andreas, Mueller-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 ORCID: 0000-0003-2695-5799, 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 ORCID: 0000-0002-5249-3316, Chuchalin, Alexander, Babadjanova, Gulja, Pantelejeva, Galina, Abramova, Lilia I., Tiganov, Alexander S., Polonikov, Alexey ORCID: 0000-0001-6280-247X, Khusnutdinova, Elza, Alda, Martin ORCID: 0000-0001-9544-3944, Cruceanu, Cristiana, Rouleau, Guy A., Turecki, Gustavo ORCID: 0000-0003-4075-2736, Laprise, Catherine ORCID: 0000-0001-5526-9945, Rivas, Fabio, Mayoral, Fermin, Kogevinas, Manolis ORCID: 0000-0002-9605-0461, Grigoroiu-Serbanescu, Maria ORCID: 0000-0002-1304-6687, Becker, Tim, Schulze, Thomas G., Rietschel, Marcella, Cichon, Sven ORCID: 0000-0002-9475-086X, Fier, Heide and Noethen, Markus M. (2017). Identification of shared risk loci and pathways for bipolar disorder and schizophrenia. PLoS One, 12 (2). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Forstner, Andreas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hecker, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maaser, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinbold, Celine S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muehleisen, Thomas W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leber, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strohmaier, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Degenhardt, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Treutlein, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mattheisen, ManuelUNSPECIFIEDorcid.org/0000-0002-8442-493XUNSPECIFIED
Schumacher, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Streit, FabianUNSPECIFIEDorcid.org/0000-0003-1080-4339UNSPECIFIED
Meier, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herms, StefanUNSPECIFIEDorcid.org/0000-0002-2786-8200UNSPECIFIED
Hoffmann, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacour, AndreUNSPECIFIEDorcid.org/0000-0003-2692-2583UNSPECIFIED
Witt, Stephanie H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reif, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Myhsok, BertramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lucae, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarz, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vedder, HelmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kammerer-Ciernioch, JuttaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfennig, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bauer, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hautzinger, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moebus, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schenk, Lorena M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, Sascha B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sivalingam, SugirthanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czerski, Piotr M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauser, JoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lissowska, JolantaUNSPECIFIEDorcid.org/0000-0003-2695-5799UNSPECIFIED
Szeszenia-Dabrowska, NeonilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brennan, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McKay, James D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wright, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitchell, Philip B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fullerton, Janice M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schofield, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montgomery, Grant W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Medland, Sarah E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gordon, Scott D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, Nicholas G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krasnov, ValeryUNSPECIFIEDorcid.org/0000-0002-5249-3316UNSPECIFIED
Chuchalin, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Babadjanova, GuljaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pantelejeva, GalinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abramova, Lilia I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tiganov, Alexander S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Polonikov, AlexeyUNSPECIFIEDorcid.org/0000-0001-6280-247XUNSPECIFIED
Khusnutdinova, ElzaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alda, MartinUNSPECIFIEDorcid.org/0000-0001-9544-3944UNSPECIFIED
Cruceanu, CristianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rouleau, Guy A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turecki, GustavoUNSPECIFIEDorcid.org/0000-0003-4075-2736UNSPECIFIED
Laprise, CatherineUNSPECIFIEDorcid.org/0000-0001-5526-9945UNSPECIFIED
Rivas, FabioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayoral, FerminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kogevinas, ManolisUNSPECIFIEDorcid.org/0000-0002-9605-0461UNSPECIFIED
Grigoroiu-Serbanescu, MariaUNSPECIFIEDorcid.org/0000-0002-1304-6687UNSPECIFIED
Becker, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulze, Thomas G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rietschel, MarcellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cichon, SvenUNSPECIFIEDorcid.org/0000-0002-9475-086XUNSPECIFIED
Fier, HeideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-239931
DOI: 10.1371/journal.pone.0171595
Journal or Publication Title: PLoS One
Volume: 12
Number: 2
Date: 2017
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; DORSOLATERAL PREFRONTAL CORTEX; LONG-TERM POTENTIATION; PSYCHIATRIC-DISORDERS; GENE-EXPRESSION; ENRICHMENT; COMMON; METAANALYSIS; POPULATIONS; GLUTAMATEMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23993

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