Identification of shared risk loci and pathways for bipolar disorder and schizophrenia
| العنوان: | Identification of shared risk loci and pathways for bipolar disorder and schizophrenia |
|---|---|
| المؤلفون: | Fabian Streit, Peter R. Schofield, Stefan Herms, James McKay, Jana Strohmaier, Céline S. Reinbold, Bertram Müller-Myhsok, Adam Wright, Sascha B. Fischer, Markus Schwarz, Susanne Moebus, Joanna Hauser, Neonila Szeszenia-Dabrowska, Michael Bauer, Andrea Hofmann, Jens Treutlein, Thomas G. Schulze, Andreas Reif, Philip B. Mitchell, Manuel Mattheisen, Martin Alda, Janice M. Fullerton, Per Hoffmann, Maria Grigoroiu-Serbanescu, Jolanta Lissowska, Gulja Babadjanova, Guy A. Rouleau, Markus M. Nöthen, Sandra Meier, Elza Khusnutdinova, Susanne Lucae, Johannes Schumacher, Catherine Laprise, Alexey Polonikov, Cristiana Cruceanu, Nicholas G. Martin, Markus Leber, Scott D. Gordon, Valery Krasnov, Fabio Rivas, Thomas W. Mühleisen, Sugirthan Sivalingam, Alexander S. Tiganov, Marcella Rietschel, Lorena M. Schenk, Piotr M. Czerski, Heide Fier, Andrea Pfennig, Jutta Kammerer-Ciernioch, André Lacour, Lilia I. Abramova, Fermín Mayoral, Manolis Kogevinas, Stephanie H. Witt, Sven Cichon, Grant W. Montgomery, Helmut Vedder, Franziska Degenhardt, Julian Hecker, Tim Becker, Galina Pantelejeva, Paul Brennan, Anna Maaser, Wolfgang Maier, Andreas J. Forstner, Sarah E. Medland, Alexander Chuchalin, Gustavo Turecki, Martin Hautzinger |
| المساهمون: | Nofer Institute of Occupational Medicine, Łódź, Poland, Walss-Bass, Consuelo |
| المصدر: | PLOS ONE PLoS ONE, Vol 12, Iss 2, p e0171595 (2017) PLOS ONE 12(2), e0171595 (2017). doi:10.1371/journal.pone.0171595 Recercat. Dipósit de la Recerca de Catalunya instname Forstner, A J, Hecker, J, Hofmann, A, Maaser, A, Reinbold, C S, Mühleisen, T W, Leber, M, Strohmaier, J, Degenhardt, F, Treutlein, J, Mattheisen, M, Schumacher, J, Streit, F, Meier, S, Herms, S, Hoffmann, P, Lacour, A, Witt, S H, Reif, A, Müller-Myhsok, B, Lucae, S, Maier, W, Schwarz, M, Vedder, H, Kammerer-Ciernioch, J, Pfennig, A, Bauer, M, Hautzinger, M, Moebus, S, Schenk, L M, Fischer, S B, Sivalingam, S, Czerski, P M, Hauser, J, Lissowska, J, Szeszenia-Dabrowska, N, Brennan, P, McKay, J D, Wright, A, Mitchell, P B, Fullerton, J M, Schofield, P R, Montgomery, G W, Medland, S E, Gordon, S D, Martin, N G, Krasnov, V, Chuchalin, A, Babadjanova, G, Pantelejeva, G, Abramova, L I, Tiganov, A S, Polonikov, A, Khusnutdinova, E, Alda, M, Cruceanu, C, Rouleau, G A, Turecki, G, Laprise, C, Rivas, F, Mayoral, F, Kogevinas, M, Grigoroiu-Serbanescu, M, Becker, T, Schulze, T G, Rietschel, M, Cichon, S, Fier, H & Nöthen, M M 2017, ' Identification of shared risk loci and pathways for bipolar disorder and schizophrenia ', PLOS ONE, vol. 12, no. 2, pp. e0171595 . https://doi.org/10.1371/journal.pone.0171595Test PLoS one 12(2), e0171595 (2017). doi:10.1371/journal.pone.0171595 PLoS ONE Dipòsit Digital de la UB Universidad de Barcelona |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Linkage disequilibrium, Bipolar Disorder, Genetic Linkage, Test Statistics, Medizin, lcsh:Medicine, Genome-wide association study, Bioinformatics, Biochemistry, Linkage Disequilibrium, Database and Informatics Methods, Mathematical and Statistical Techniques, 0302 clinical medicine, Medicine and Health Sciences, Manic-depressive illness, genetics [Schizophrenia], lcsh:Science, Genetics, bipolar disorder, Multidisciplinary, Trastorn bipolar, Neurochemistry, Genomics, Neurotransmitters, Genomic Databases, 3. Good health, genomic medicine, Schizophrenia, Physical Sciences, Esquizofrènia, metabolism [Schizophrenia], ddc:500, Glutamate, Statistics (Mathematics), Research Article, Signal Transduction, Risk, Quantitative Trait Loci, Single-nucleotide polymorphism, glutamate, Quantitative trait locus, Biology, Research and Analysis Methods, Polymorphism, Single Nucleotide, 03 medical and health sciences, Genomic Medicine, Genetic linkage, Mental Health and Psychiatry, Genome-Wide Association Studies, medicine, SNP, Humans, Genetic Predisposition to Disease, Bipolar disorder, ddc:610, Statistical Methods, metabolism [Bipolar Disorder], Mood Disorders, lcsh:R, Biology and Life Sciences, Computational Biology, genetic loci, Human Genetics, Genome Analysis, medicine.disease, Biological Databases, 030104 developmental biology, Genetic Loci, lcsh:Q, Mathematics, 030217 neurology & neurosurgery, genetics [Bipolar Disorder], Neuroscience, Meta-Analysis, Genome-Wide Association Study |
| الوصف: | 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. Funding: 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. |
| وصف الملف: | application/pdf; application/octet-stream |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::50f1509098e7933373fd51a3a013c15fTest https://hdl.handle.net/21.11116/0000-0001-84C2-E21.11116/0000-0001-84C0-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....50f1509098e7933373fd51a3a013c15f |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |