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dc.contributor.authorForstner, Andreas J
dc.contributor.authorHecker, Julian
dc.contributor.authorHofmann, Andrea
dc.contributor.authorMaaser, Anna
dc.contributor.authorReinbold, Céline S
dc.contributor.authorMühleisen, Thomas W
dc.contributor.authorLeber, Markus
dc.contributor.authorStrohmaier, Jana
dc.contributor.authorDegenhardt, Franziska
dc.contributor.authorTreutlein, Jens
dc.contributor.authorMattheisen, Manuel
dc.contributor.authorSchumacher, Johannes
dc.contributor.authorStreit, Fabian
dc.contributor.authorMeier, Sandra
dc.contributor.authorHerms, Stefan
dc.contributor.authorHoffmann, Per
dc.contributor.authorLacour, André
dc.contributor.authorWitt, Stephanie H
dc.contributor.authorReif, Andreas
dc.contributor.authorMüller-Myhsok, Bertram
dc.contributor.authorLucae, Susanne
dc.contributor.authorMaier, Wolfgang
dc.contributor.authorSchwarz, Markus
dc.contributor.authorVedder, Helmut
dc.contributor.authorKammerer-Ciernioch, Jutta
dc.contributor.authorPfennig, Andrea
dc.contributor.authorBauer, Michael
dc.contributor.authorHautzinger, Martin
dc.contributor.authorMoebus, Susanne
dc.contributor.authorSchenk, Lorena M
dc.contributor.authorFischer, Sascha B
dc.contributor.authorSivalingam, Sugirthan
dc.contributor.authorCzerski, Piotr M
dc.contributor.authorHauser, Joanna
dc.contributor.authorLissowska, Jolanta
dc.contributor.authorSzeszenia-Dabrowska, Neonila
dc.contributor.authorBrennan, Paul
dc.contributor.authorMcKay, James D
dc.contributor.authorWright, Adam
dc.contributor.authorMitchell, Philip B
dc.contributor.authorFullerton, Janice M
dc.contributor.authorSchofield, Peter R
dc.contributor.authorMontgomery, Grant W
dc.contributor.authorMedland, Sarah E
dc.contributor.authorGordon, Scott D
dc.contributor.authorMartin, Nicholas G
dc.contributor.authorKrasnov, Valery
dc.contributor.authorChuchalin, Alexander
dc.contributor.authorBabadjanova, Gulja
dc.contributor.authorPantelejeva, Galina
dc.contributor.authorAbramova, Lilia I
dc.contributor.authorTiganov, Alexander S
dc.contributor.authorPolonikov, Alexey
dc.contributor.authorKhusnutdinova, Elza
dc.contributor.authorAlda, Martin
dc.contributor.authorCruceanu, Cristiana
dc.contributor.authorRouleau, Guy A
dc.contributor.authorTurecki, Gustavo
dc.contributor.authorLaprise, Catherine
dc.contributor.authorRivas, Fabio
dc.contributor.authorMayoral, Fermin
dc.contributor.authorKogevinas, Manolis
dc.contributor.authorGrigoroiu-Serbanescu, Maria
dc.contributor.authorBecker, Tim
dc.contributor.authorSchulze, Thomas G
dc.contributor.authorRietschel, Marcella
dc.contributor.authorCichon, Sven
dc.contributor.authorFier, Heide
dc.contributor.authorNöthen, Markus M
dc.date.accessioned2017-08-24T10:57:34Z
dc.date.available2017-08-24T10:57:34Z
dc.date.issued2017
dc.identifier.citationPLoS ONE 2017, 12 (2):e0171595en
dc.identifier.issn1932-6203
dc.identifier.pmid28166306
dc.identifier.doi10.1371/journal.pone.0171595
dc.identifier.urihttp://hdl.handle.net/10146/618139
dc.description.abstractBipolar 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.
dc.description.sponsorshipFunding: The study was supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under the auspices of the e:Med Programme (grant 01ZX1314A to M.M.N. and S.C., grant 01ZX1314G to M.R.). M.M.N. is a member of the DFG-funded Excellence-Cluster ImmunoSensation. M.M.N. also received support from the Alfried Krupp von Bohlen und Halbach-Stiftung. The study was supported by the German Research Foundation (DFG; grant FOR2107; RI908/11-1 to M.R.; NO246/10-1 to M.M.N.). The study was also supported by the Swiss National Science Foundation (SNSF, grant 156791 to S.C.). M.G.S. received grant no. 89/2012 from UEFISCDI, Romania. Canadian patients were genotyped within the ConLiGen project (www.ConLiGen.org), with the support of a grant from the DFG to M.R., M.B., and T.G.S. (RI 908/7-1). Controls for Germany II were drawn from the Heinz Nixdorf Recall Study (HNR) cohort, which was established with the support of the Heinz Nixdorf Foundation. Recruitment of the Australian sample was supported by an Australian NHMRC program grant (number 1037196). The recruitment of the Canadian patients was supported by a grant from the Canadian Institutes of Health Research #64410 to M.A. The study also used data generated by the GABRIEL consortium (controls for the sample Russia). Funding for the generation of these data was provided by the European Commission as part of GABRIEL contract number 018996 under the Integrated Program LSH-2004-1.2.5-1. Post genomic approaches to understand the molecular basis of asthma aiming at a preventive or therapeuticcontrol and the Wellcome Trust under award 084703. Canadian controls were drawn from the French Canadian study (SLSJ), which was supported in part by the Canada research Chair Environment and genetics of respiratory diseases and allergy, the Canadian Institutes of Health Research (Operating grant No. MOP-13506), and the Quebec Respiratory Network of the Fonds de rechercheen Sante du QueÂbec (FRQS). Polish controls were recruited by the International Agency for Research on Cancer (IARC)/Centre National de Genotypage (CNG) GWAS Initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.language.isoenen
dc.relation.urlhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171595en
dc.rightsArchived with thanks to PloS oneen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectbipolar disorderen
dc.subjectgenetic locien
dc.subjectglutamateen
dc.subjectgenomic medicineen
dc.titleIdentification of shared risk loci and pathways for bipolar disorder and schizophrenia.en
dc.typeArticleen
dc.contributor.departmentNofer Institute of Occupational Medicine, Łódź, Polanden
dc.identifier.journalPloS ONEen
refterms.dateFOA2018-12-17T17:59:52Z
html.description.abstractBipolar 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.


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