Manuel Mattheisen

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Thomas W Mühleisen, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany [3] Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, D-52425 Jülich, Germany [4].
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  • Markus Leber, 1] Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, D-53127 Bonn, Germany [2] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, D-53175 Bonn, Germany [3].
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  • Thomas G Schulze, 1] Department of Psychiatry and Psychotherapy, University of Go¨ttingen, D-37075 Göttingen, Germany [2].
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  • Jana Strohmaier, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Franziska Degenhardt, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany.
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  • Jens Treutlein, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Manuel Mattheisen
  • Andreas J Forstner, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany.
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  • Johannes Schumacher, LUKKET: 2012 Afd. for Skovdrift og Træprodukter, Denmark
  • René Breuer, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Sandra Meier, Denmark
  • Stefan Herms, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany [3] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel CH-4012, Switzerland.
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  • Per Hoffmann, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany [3] Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, D-52425 Jülich, Germany [4] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel CH-4012, Switzerland.
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  • André Lacour, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, D-53175 Bonn, Germany.
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  • Stephanie H Witt, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
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  • Andreas Reif, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, D-97070 Würzburg, Germany.
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  • Bertram Müller-Myhsok, 1] Statistical Genetics, Department of Translational Psychiatry, Max Planck Institute of Psychiatry, D-80804 Munich, Germany [2] Munich Cluster for Systems Neurology (SyNergy), D-80336 Munich, Germany [3] Institute of Translational Medicine, University of Liverpool, L69 3BX Liverpool, UK.
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  • Susanne Lucae, Statistical Genetics, Department of Translational Psychiatry, Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
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  • Wolfgang Maier, Department of Psychiatry, University of Bonn, D-53127 Bonn, Germany.
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  • Markus Schwarz, Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
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  • Helmut Vedder, Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
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  • Jutta Kammerer-Ciernioch, Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
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  • Andrea Pfennig, Department of Psychiatry and Psychotherapy, University Hospital, D-01307 Dresden, Germany.
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  • Michael Bauer, Department of Psychiatry and Psychotherapy, University Hospital, D-01307 Dresden, Germany.
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  • Martin Hautzinger, Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, D-72074 Tübingen, Germany.
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  • Susanne Moebus, Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen, D-45147 Essen, Germany.
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  • Lutz Priebe, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany.
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  • Piotr M Czerski, Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland.
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  • Joanna Hauser, Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland.
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  • Jolanta Lissowska, Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw PL-02-781, Poland.
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  • Neonila Szeszenia-Dabrowska, Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz PL-91-348, Poland.
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  • Paul Brennan, Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
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  • James D McKay, Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
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  • Adam Wright, 1] School of Psychiatry, University of New South Wales, Randwick, New South Wales 2052, Australia [2] Black Dog Institute, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.
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  • Philip B Mitchell, 1] School of Psychiatry, University of New South Wales, Randwick, New South Wales 2052, Australia [2] Black Dog Institute, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.
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  • Janice M Fullerton, 1] Neuroscience Research Australia, Randwick, Sydney, New South Wales 2031, Australia [2] School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia.
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  • Peter R Schofield, 1] Neuroscience Research Australia, Randwick, Sydney, New South Wales 2031, Australia [2] School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia.
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  • Grant W Montgomery, Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
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  • Sarah E Medland, Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
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  • Scott D Gordon, Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
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  • Nicholas G Martin, Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
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  • Valery Krasnow, Moscow Research Institute of Psychiatry, Moscow 107258, Russian Federation.
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  • Alexander Chuchalin, Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation.
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  • Gulja Babadjanova, Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation.
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  • Galina Pantelejeva, Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
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  • Lilia I Abramova, Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
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  • Alexander S Tiganov, Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
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  • Alexey Polonikov, Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk 305041, Russian Federation.
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  • Elza Khusnutdinova, Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa 450054, Russian Federation.
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  • Martin Alda, 1] Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada B3H 2E2 [2] The International Group for the Study of Lithium-Treated Patients (IGSLI), Berlin, Germany.
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  • Paul Grof, 1] The International Group for the Study of Lithium-Treated Patients (IGSLI), Berlin, Germany [2] Mood Disorders Center of Ottawa, Ottawa, Ontario, Canada K1G 4G3 [3] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.
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  • Guy A Rouleau, Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, Québec, Canada H3G 1A4.
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  • Gustavo Turecki, Department of Psychiatry, Douglas Hospital Research Institute, McGill University, Montreal, Quebec, Canada H4H 1R3.
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  • Catherine Laprise, Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, Canada G7H 2B1.
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  • Fabio Rivas, Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain.
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  • Fermin Mayoral, Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain.
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  • Manolis Kogevinas, Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain.
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  • Maria Grigoroiu-Serbanescu, Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest RO-041914, Romania.
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  • Peter Propping, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany.
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  • Tim Becker, 1] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, D-53175 Bonn, Germany [2] Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, D-53127 Bonn, Germany.
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  • Marcella Rietschel, 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany [2].
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  • Markus M Nöthen, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany [3].
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  • Sven Cichon, 1] Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, D-53127 Bonn, Germany [3] Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, D-52425 Jülich, Germany [4] Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel CH-4012, Switzerland [5].
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.
Original languageEnglish
JournalNature Communications
Volume5
Pages (from-to)3339
ISSN2041-1723
DOIs
Publication statusPublished - 2014

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