Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder
| Autor: | Susanne Lucae, Gerhard Schratt, M.P. Schwarz, Adam Wright, Martin Hautzinger, Philip B. Mitchell, Sharof Khudayberdiev, Nicholas G. Martin, W. Maier, Johannes Schumacher, Piotr M. Czerski, Markus M. Nöthen, Janice M. Fullerton, Susanne Meier, Cristiana Cruceanu, Tim Becker, Jana Strohmaier, Peter R. Schofield, Stefan Herms, Guy A. Rouleau, André Lacour, Thomas G. Schulze, Sugirthan Sivalingam, Galina Pantelejeva, Gustavo Turecki, Elza Khusnutdinova, Lilia I. Abramova, Catherine Laprise, Fermín Mayoral, Stephanie H. Witt, Jens Treutlein, Joanna Hauser, James D. McKay, Sven Cichon, Martin Alda, Bertram Müller-Myhsok, Andreas Reif, Michael Bauer, Manuel Mattheisen, Franziska Degenhardt, Marcella Rietschel, Helmut Vedder, Peter Propping, Alexey Polonikov, Neonilia Szeszenia-Dabrowska, S. E. Medland, Scott D. Gordon, Markus Leber, Valery Krasnov, Lutz Priebe, Alexander Chuchalin, Susanne Moebus, Peter Hoffmann, Gulia Babadjanova, A Verhaert, Thomas W. Mühleisen, M Grigoroiu-Serbanescu, Jolanta Lissowska, Alexander S. Tiganov, Simon Sumer, Henning G. Schulz, Andreas Hofmann, Grant W. Montgomery, Paul Brennan, Anna Maaser, Andreas J. Forstner, Fabio Rivas, Manolis Kogevinas, Andrea Pfennig, Jutta Kammerer-Ciernioch, René Breuer |
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| Přispěvatelé: | [Forsther,AJ, Hofmann,A, Maaser,A, Mühleisen,TW, Degenhardt,F, Schumacher,J, Herms,S, Hoffmann,P, Priebe,L, Sivalingam,S, Verhaert,A, Propping,P, Cichon,S, Nöthen,MM, ] Institute of Human Genetics, University of Bonn, Bonn, Germany. [Forsther,AJ, Nöthen,MM] Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. [Sumer,S, Khudayberdiev,S, Schratt,G] Institute of Physiological Chemistry, Philipps-University Marburg, Marburg, Germany. [Mühleisen,TW, Cichon,S] Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany. [Leber,M, Becker,T] Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany. [Schulze,TG] Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany. [Strohmaier,J, Treutlein,J, Breuer,R, Meier,S, Witt,SH, Rietschel,M] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Heidelberg, Germany. [Mattheisen,M] Department of Biomedicine, Aarhus University, Aarhus, Denmark. Institute for Genomics Mathematics, University of Bonn, Bonn, Germany. [Meier,S] National Center Register-Based Research, Aarhus University, Aarhus, Denmark. [Herms,S, Cichon,S] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland. [Lacour,A] German Center for Neurodegenerative Diseases, Bonn, Germany. [Reif,A] Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt am Main, Frankfurt, Germany. [Müller-Myhsok,B, Lucae,S] Max Planck Institute of Psychiatry, Munich, Germany. [Müller-Myhsok,B ] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. University of Liverpool, Institute of Translational Medicine, Liverpool, UK. [Maier,W] Department of Psychiatry, University of Bonn, Bonn, Germany. [Schwarz,M, Vedder,H] Psychiatric Center Nordbaden, Wiesloch, Germany. [Kammerer-Ciernioch,J] Center of Psychiatry Weinsberg, Weinsberg, Germany. [Pfennig,A, Bauer,M] Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany. [Hautzinger,M] Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, Tübingen, Germany. [Moebus,S] Institute of Medical Informatics, Biometry and Epidemiology, University Duisburg-Essen, Essen, Germany. [Shultz,H] Cologne Center for Genomics, University of Cologne, Cologne, Germany. [Czerski,PM, Hauser,J] Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland. [Lossowska,J] Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology Warsaw, Warsaw, Poland. [Szeszenia-Dabrowska,N] Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland. [Brennan,P] Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France. [Mckay,JD] Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France. [Wright,A, Mitchell,PB] School of Psychiatry, University of New South Wales, Randwick, NSW, Australia. Black Dog Institute, Prince of Wales Hospital, Randwick, NSW, Australia. [Fullerton,JM, Schofield,PR] Neuroscience Research Australia, Sydney, NSW, Australia. School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. [Montgomery,GW, Medland,SE, Gordon,SD, Martin, NG] Queensland Institute of Medical Research, Brisbane, QLD, Australia. [Krasnov ,V] Moscow Research Institute of Psychiatry, Moscow, Russian Federation. [Chuchalin,A, Babadjanova,G] Institute of Pulmonology, Russian State Medical University, Moscow, Russian Federation. [Pantelejeva,G, Abramova,LI, Toganoc,AS] Russian Academy of Medical Sciences, Mental Health Research Center, Moscow, Russian Federation. [Polonikov,A] Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russian Federation. [Khusnutdinova,E] Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russian Federation. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russian Federation. [Alda,M] Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. National Institute of Mental Health, Klecany, Czech Republic. [Cruceanu,C, Rouleau,GA] Montreal Neurological Institute, McGill University, Montreal, QC, Canada. [Cruceanu,C, Turecki,G] Department of Human Genetics, McGill University, Montreal, QC, Canada. McGill Group for Suicide Studies and Douglas Research Institute, Montreal, QC, Canada. [Turecki,G] Department of Psychiatry, McGill University, Montreal, QC, Canada. [Laprise,C] Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Chicoutimi, QC, Canada. [Rivas,F, Mayoral,F] Department of Psychiatry, Hospital Regional Universitario, Biomedical Institute of Malaga, Malaga, Spain. [Kogevinas,M] Center for Research in Environmental Epidemiology, Barcelona, Spain. [Grigoroiu-Serbanescu,M] Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania., 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 MMN and SC, grant 01ZX1314G to MR, grant 01ZX1314J to BMM), and through e:AtheroSysMed (Systems medicine of myocardial infarction and stroke, grant 01ZX1313B to BMM). MMN is a member of the DFGfunded Excellence-Cluster ImmunoSensation. MMN 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 MR, SCHR1136/3-1 to GS, NO246/10-1 to MMN). MG-S received the 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 Deutsche Forschungsgemeinschaft to MR, MB and TGS (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 MA. 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 therapeutic control 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 recherche en Santé du Québec (FRQS). Polish controls were recruited by the International Agency for Research on Cancer (IARC)/Centre National de Genotypage (CNG) GWAS Initiative. |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Bipolar Disorder
Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus [Medical Subject Headings] Medizin Psychiatry and Psychology::Mental Disorders::Mood Disorders::Affective Disorders Psychotic::Bipolar Disorder [Medical Subject Headings] Dendritic spine morphogenesis Genomics Genome-wide association study Plasticidad neuronal Biology Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleic Acids::RNA::RNA Untranslated::RNA Small Untranslated::MicroRNAs [Medical Subject Headings] Rats Sprague-Dawley Ratas Cellular and Molecular Neuroscience microRNA Hipocampo medicine Animals Humans Genetic Predisposition to Disease genetics [MicroRNAs] ddc:610 Bipolar disorder genetics [Genetic Predisposition to Disease] Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings] Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Neuronal Plasticity [Medical Subject Headings] Gene Biological Psychiatry Genetics MicroARN Neuron projection Trastorno bipolar Predisposición genética a la enfermedad medicine.disease Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings] Rats 3. Good health Disease Models Animal MicroRNAs Psychiatry and Mental health Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings] Schizophrenia Original Article Prevalencia genetics [Bipolar Disorder] statistics & numerical data [Genome-Wide Association Study] Genome-Wide Association Study |
| Zdroj: | Forstner, A J, Hofmann, A, Maaser, A, Sumer, S, Khudayberdiev, S, Mühleisen, T W, Leber, M, Schulze, T G, Strohmaier, J, Degenhardt, F, Treutlein, J, Mattheisen, M, Schumacher, J, Breuer, R, 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, Priebe, L, Sivalingam, S, Verhaert, A, Schulz, H, 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, Propping, P, Becker, T, Rietschel, M, Cichon, S, Schratt, G & Nöthen, M M 2015, ' Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder ', Translational Psychiatry, vol. 5, pp. e678 . https://doi.org/10.1038/tp.2015.159 Forstner, A J, Hofmann, A, Maaser, A, Sumer, S, Khudayberdiev, S, Mühleisen, T W, Leber, M, Schulze, T G, Strohmaier, J, Degenhardt, F, Treutlein, J, Mattheisen, M, Schumacher, J, Breuer, R, 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, Priebe, L, Sivalingam, S, Verhaert, A, Schulz, H, 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, Propping, P, Becker, T, Rietschel, M, Cichon, S, Schratt, G & Nöthen, M M 2015, ' Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder ', Translational psychiatry, vol. 5, e678 . https://doi.org/10.1038/tp.2015.159 TRANSLATIONAL PSYCHIATRY Translational Psychiatry Translational Psychiatry 5(11), e678 (2015). doi:10.1038/tp.2015.159 Translational Psychiatry 5(11), e678-e678 (2015). doi:10.1038/tp.2015.159 |
| DOI: | 10.1038/tp.2015.159 |
| Popis: | Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD. |
| Databáze: | OpenAIRE |
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