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 particular schizophrenia (SCZ). The genes underlying this etiological overlap remai...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/107944 |
| Acceso en línea: | https://hdl.handle.net/2445/107944 |
| Access Level: | acceso abierto |
| Palabra clave: | Trastorn bipolar Esquizofrènia Manic-depressive illness Schizophrenia |
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Identification of shared risk loci and pathways for bipolar disorder and schizophreniaForstner, Andreas J.Hecker, JulianHofmann, AndreaReinbold, Celine S.Mühleisen, Thomas W.Leber, MarkusStrohmaier, JanaDegenhardt, FranziskaTreutlein, JensMattheisen, ManuelSchumacher, JohannesStreit, FabianMeier, SandraHerms, StefanHoffmann, PerLacour, AndréWitt, Stephanie H.Maaser, AnnaReif, AndreasMüller-Myhsok, BertramLucae, SusanneMaier, WolfgangSchwarz, MarkusVedder, HelmutKammerer-Ciernioch, JuttaPfennig, AndreaBauer, MichaelHautzinger, MartinMoebus, SusanneSchenk, Lorena M.Fischer, Sascha B.Sivalingam, SugirthanCzerski, Piotr M.Hauser, JoannaLissowska, JolantaSzeszenia-Dabrowska, NeonilaBrennan, PaulMcKay, James D.Wright, AdamMitchell, Philip B.Fullerton, Janice M.Schofield, Peter R.Montgomery, Grant W.Medland, Sarah E.Gordon, Scott D.Martin, Nicholas G.Krasnov, ValeryChuchalin, AlexanderBabadjanova, GuljaPantelejeva, GalinaAbramova, Lilia I.Tiganov, Alexander S.Polonikov, AlexeyKhusnutdinova, ElzaAlda, MartinCruceanu, CristianaRouleau, Guy A.Turecki, GustavoLaprise, CatherineRivas, FabioMayoral, FerminKogevinas, ManolisGrigoroiu-Serbanescu, MariaBecker, TimSchulze, Thomas G.Rietschel, ManolisCichon, SvenFier, HeideNöthen, Markus M.Trastorn bipolarEsquizofrèniaManic-depressive illnessSchizophreniaBipolar 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.Public Library of Science (PLoS)2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/107944Articles publicats en revistes (ISGlobal)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0171595PLoS One, 2017, vol. 12, num. 2, p. e0171595http://dx.doi.org/10.1371/journal.pone.0171595cc by (c) Forstner et al., 2017http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1079442026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia |
| title |
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia |
| spellingShingle |
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia Forstner, Andreas J. Trastorn bipolar Esquizofrènia Manic-depressive illness Schizophrenia |
| title_short |
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia |
| title_full |
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia |
| title_fullStr |
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia |
| title_full_unstemmed |
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia |
| title_sort |
Identification of shared risk loci and pathways for bipolar disorder and schizophrenia |
| dc.creator.none.fl_str_mv |
Forstner, Andreas J. Hecker, Julian Hofmann, Andrea Reinbold, Celine 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. Maaser, Anna 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, Manolis Cichon, Sven Fier, Heide Nöthen, Markus M. |
| author |
Forstner, Andreas J. |
| author_facet |
Forstner, Andreas J. Hecker, Julian Hofmann, Andrea Reinbold, Celine 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. Maaser, Anna 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, Manolis Cichon, Sven Fier, Heide Nöthen, Markus M. |
| author_role |
author |
| author2 |
Hecker, Julian Hofmann, Andrea Reinbold, Celine 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. Maaser, Anna 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, Manolis Cichon, Sven Fier, Heide Nöthen, Markus M. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Trastorn bipolar Esquizofrènia Manic-depressive illness Schizophrenia |
| topic |
Trastorn bipolar Esquizofrènia Manic-depressive illness Schizophrenia |
| description |
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. |
| publishDate |
2017 |
| dc.date.none.fl_str_mv |
2017 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://hdl.handle.net/2445/107944 |
| url |
https://hdl.handle.net/2445/107944 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0171595 PLoS One, 2017, vol. 12, num. 2, p. e0171595 http://dx.doi.org/10.1371/journal.pone.0171595 |
| dc.rights.none.fl_str_mv |
cc by (c) Forstner et al., 2017 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess |
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cc by (c) Forstner et al., 2017 http://creativecommons.org/licenses/by/3.0/es/ |
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openAccess |
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application/pdf |
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Public Library of Science (PLoS) |
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Public Library of Science (PLoS) |
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Articles publicats en revistes (ISGlobal) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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