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

Thomas W Mühleisen¹, Markus Leber², Thomas G Schulze³, Jana Strohmaier⁴, Franziska Degenhardt⁵, Jens Treutlein⁴, Manuel Mattheisen⁶, Andreas J Forstner⁵, Johannes Schumacher⁵, René Breuer⁴, Sandra Meier⁷, Stefan Herms⁸, Per Hoffmann⁹, André Lacour¹⁰, Stephanie H Witt⁴, Andreas Reif¹¹, Bertram Müller-Myhsok¹², Susanne Lucae¹³, Wolfgang Maier¹⁴, Markus Schwarz¹⁵, Helmut Vedder¹⁵, Jutta Kammerer-Ciernioch¹⁵, Andrea Pfennig¹⁶, Michael Bauer¹⁶, Martin Hautzinger¹⁷, Susanne Moebus¹⁸, Lutz Priebe⁵, Piotr M Czerski¹⁹, Joanna Hauser¹⁹, Jolanta Lissowska²⁰, Neonila Szeszenia-Dabrowska²¹, Paul Brennan²², James D McKay²³, Adam Wright²⁴, Philip B Mitchell²⁴, Janice M Fullerton²⁵, Peter R Schofield²⁵, Grant W Montgomery²⁶, Sarah E Medland²⁶, Scott D Gordon²⁶, Nicholas G Martin²⁶, Valery Krasnow²⁷, Alexander Chuchalin²⁸, Gulja Babadjanova²⁸, Galina Pantelejeva²⁹, Lilia I Abramova²⁹, Alexander S Tiganov²⁹, Alexey Polonikov³⁰, Elza Khusnutdinova³¹, Martin Alda³², Paul Grof³³, Guy A Rouleau³⁴, Gustavo Turecki³⁵, Catherine Laprise³⁶, Fabio Rivas³⁷, Fermin Mayoral³⁷, Manolis Kogevinas³⁸, Maria Grigoroiu-Serbanescu³⁹, Peter Propping⁴⁰, Tim Becker⁴¹, Marcella Rietschel⁷, Markus M Nöthen⁴², Sven Cichon⁴³

Affiliations

¹ 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].
² 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].
³ 1] Department of Psychiatry and Psychotherapy, University of Go¨ttingen, D-37075 Göttingen, Germany [2].
⁴ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
⁵ 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.
⁶ 1] Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark [2] Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany.
⁷ 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany [2].
⁸ 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.
⁹ 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.
¹⁰ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, D-53175 Bonn, Germany.
¹¹ Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, D-97070 Würzburg, Germany.
¹² 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.
¹³ Statistical Genetics, Department of Translational Psychiatry, Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
¹⁴ Department of Psychiatry, University of Bonn, D-53127 Bonn, Germany.
¹⁵ Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
¹⁶ Department of Psychiatry and Psychotherapy, University Hospital, D-01307 Dresden, Germany.
¹⁷ Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, D-72074 Tübingen, Germany.
¹⁸ Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen, D-45147 Essen, Germany.
¹⁹ Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland.
²⁰ Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw PL-02-781, Poland.
²¹ Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz PL-91-348, Poland.
²² Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
²³ Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
²⁴ 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.
²⁵ 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.
²⁶ Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
²⁷ Moscow Research Institute of Psychiatry, Moscow 107258, Russian Federation.
²⁸ Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation.
²⁹ Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
³⁰ Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk 305041, Russian Federation.
³¹ Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa 450054, Russian Federation.
³² 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.
³³ 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.
³⁴ Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, Québec, Canada H3G 1A4.
³⁵ Department of Psychiatry, Douglas Hospital Research Institute, McGill University, Montreal, Quebec, Canada H4H 1R3.
³⁶ Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, Canada G7H 2B1.
³⁷ Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain.
³⁸ Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain.
³⁹ Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest RO-041914, Romania.
⁴⁰ Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany.
⁴¹ 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.
⁴² 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].
⁴³ 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].

PMID: 24618891
DOI: 10.1038/ncomms4339

Free article

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

Thomas W Mühleisen et al. Nat Commun. 2014.

Free article

. 2014 Mar 11:5:3339.

doi: 10.1038/ncomms4339.

Authors

Affiliations

¹ 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].
² 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].
³ 1] Department of Psychiatry and Psychotherapy, University of Go¨ttingen, D-37075 Göttingen, Germany [2].
⁴ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
⁵ 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.
⁶ 1] Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark [2] Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany.
⁷ 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany [2].
⁸ 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.
⁹ 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.
¹⁰ German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, D-53175 Bonn, Germany.
¹¹ Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, D-97070 Würzburg, Germany.
¹² 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.
¹³ Statistical Genetics, Department of Translational Psychiatry, Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
¹⁴ Department of Psychiatry, University of Bonn, D-53127 Bonn, Germany.
¹⁵ Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
¹⁶ Department of Psychiatry and Psychotherapy, University Hospital, D-01307 Dresden, Germany.
¹⁷ Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, D-72074 Tübingen, Germany.
¹⁸ Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen, D-45147 Essen, Germany.
¹⁹ Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland.
²⁰ Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw PL-02-781, Poland.
²¹ Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz PL-91-348, Poland.
²² Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
²³ Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
²⁴ 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.
²⁵ 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.
²⁶ Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
²⁷ Moscow Research Institute of Psychiatry, Moscow 107258, Russian Federation.
²⁸ Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation.
²⁹ Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
³⁰ Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk 305041, Russian Federation.
³¹ Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa 450054, Russian Federation.
³² 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.
³³ 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.
³⁴ Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, Québec, Canada H3G 1A4.
³⁵ Department of Psychiatry, Douglas Hospital Research Institute, McGill University, Montreal, Quebec, Canada H4H 1R3.
³⁶ Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, Canada G7H 2B1.
³⁷ Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain.
³⁸ Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain.
³⁹ Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest RO-041914, Romania.
⁴⁰ Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany.
⁴¹ 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.
⁴² 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].
⁴³ 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].

PMID: 24618891
DOI: 10.1038/ncomms4339

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.

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

Affiliations

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

Authors

Affiliations

Abstract

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