Genome-wide association study reveals two new risk loci for bipolar disorder

Thomas W. Mühleisen, Markus Leber, Thomas G. Schulze, Jana Strohmaier, Franziska Degenhardt, Jens Treutlein, Manuel Mattheisen, Andreas J. Forstner, Johannes Schumacher, René Breuer, Sandra Meier, Stefan Herms, Per Hoffmann, André Lacour, Stephanie H. Witt, Andreas Reif, Bertram Müller-Myhsok, Susanne Lucae, Wolfgang Maier, Markus Schwarz, Helmut Vedder, Jutta Kammerer-Ciernioch, Andrea Pfennig, Michael Bauer, Martin Hautzinger, Susanne Moebus, Lutz Priebe, Piotr M. Czerski, Joanna Hauser, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Paul Brennan, James D. McKay, Adam Wright, Philip B. Mitchell, Janice M. Fullerton, Peter R. Schofield, Grant W. Montgomery, Sarah E. Medland, Scott D. Gordon, Nicholas G. Martin, Valery Krasnow, Alexander Chuchalin, Gulja Babadjanova, Galina Pantelejeva, Lilia I. Abramova, Alexander S. Tiganov, Alexey Polonikov, Elza Khusnutdinova, Martin Alda, Paul Grof, Guy A. Rouleau, Gustavo Turecki, Catherine Laprise, Fabio Rivas, Fermin Mayoral, Manolis Kogevinas, Maria Grigoroiu-Serbanescu, Peter Propping, Tim Becker, Marcella Rietschel (), Markus M. Nöthen () and Sven Cichon ()
Additional contact information
Thomas W. Mühleisen: Institute of Human Genetics, University of Bonn
Markus Leber: Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn
Thomas G. Schulze: University of Go¨ttingen
Jana Strohmaier: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University
Franziska Degenhardt: Institute of Human Genetics, University of Bonn
Jens Treutlein: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University
Manuel Mattheisen: Aarhus University
Andreas J. Forstner: Institute of Human Genetics, University of Bonn
Johannes Schumacher: Institute of Human Genetics, University of Bonn
René Breuer: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University
Sandra Meier: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University
Stefan Herms: Institute of Human Genetics, University of Bonn
Per Hoffmann: Institute of Human Genetics, University of Bonn
André Lacour: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Stephanie H. Witt: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University
Andreas Reif: Psychosomatics and Psychotherapy, University of Würzburg
Bertram Müller-Myhsok: Statistical Genetics, Max Planck Institute of Psychiatry
Susanne Lucae: Statistical Genetics, Max Planck Institute of Psychiatry
Wolfgang Maier: University of Bonn
Markus Schwarz: Psychiatric Center Nordbaden
Helmut Vedder: Psychiatric Center Nordbaden
Jutta Kammerer-Ciernioch: Psychiatric Center Nordbaden
Andrea Pfennig: University Hospital
Michael Bauer: University Hospital
Martin Hautzinger: Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen
Susanne Moebus: Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen
Lutz Priebe: Institute of Human Genetics, University of Bonn
Piotr M. Czerski: Poznan University of Medical Sciences
Joanna Hauser: Poznan University of Medical Sciences
Jolanta Lissowska: Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology
Neonila Szeszenia-Dabrowska: Nofer Institute of Occupational Medicine
Paul Brennan: Genetic Epidemiology Group, International Agency for Research on Cancer (IARC)
James D. McKay: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC)
Adam Wright: School of Psychiatry, University of New South Wales
Philip B. Mitchell: School of Psychiatry, University of New South Wales
Janice M. Fullerton: Neuroscience Research Australia
Peter R. Schofield: Neuroscience Research Australia
Grant W. Montgomery: Queensland Institute of Medical Research (QIMR)
Sarah E. Medland: Queensland Institute of Medical Research (QIMR)
Scott D. Gordon: Queensland Institute of Medical Research (QIMR)
Nicholas G. Martin: Queensland Institute of Medical Research (QIMR)
Valery Krasnow: Moscow Research Institute of Psychiatry
Alexander Chuchalin: Institute of Pulmonology, Russian State Medical University
Gulja Babadjanova: Institute of Pulmonology, Russian State Medical University
Galina Pantelejeva: Russian Academy of Medical Sciences, Mental Health Research Center
Lilia I. Abramova: Russian Academy of Medical Sciences, Mental Health Research Center
Alexander S. Tiganov: Russian Academy of Medical Sciences, Mental Health Research Center
Alexey Polonikov: Medical Genetics and Ecology, Kursk State Medical University
Elza Khusnutdinova: Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences
Martin Alda: Dalhousie University
Paul Grof: The International Group for the Study of Lithium-Treated Patients (IGSLI)
Guy A. Rouleau: Montreal Neurological Hospital and Institute, McGill University
Gustavo Turecki: Douglas Hospital Research Institute, McGill University
Catherine Laprise: Université du Québec à Chicoutimi (UQAC)
Fabio Rivas: Hospital Regional Universitario Carlos Haya
Fermin Mayoral: Hospital Regional Universitario Carlos Haya
Manolis Kogevinas: Center for Research in Environmental Epidemiology (CREAL)
Maria Grigoroiu-Serbanescu: Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital
Peter Propping: Institute of Human Genetics, University of Bonn
Tim Becker: Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn
Marcella Rietschel: Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University
Markus M. Nöthen: Institute of Human Genetics, University of Bonn
Sven Cichon: Institute of Human Genetics, University of Bonn

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: Abstract Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.

Date: 2014
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DOI: 10.1038/ncomms4339

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