title: Genome-wide association study reveals two new risk loci for bipolar disorder.
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.
authors.affiliation: 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].
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Mühleisen
authors.affiliation: 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].
authors.forename: Markus
authors.initials: M
authors.lastname: Leber
authors.affiliation: 1] Department of Psychiatry and Psychotherapy, University of Go¨ttingen, D-37075 Göttingen, Germany [2].
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Strohmaier
authors.affiliation: 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.
authors.forename: Franziska
authors.initials: F
authors.lastname: Degenhardt
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Treutlein
authors.affiliation: 1] Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark [2] Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.affiliation: 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.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Forstner
authors.affiliation: 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.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Breuer
authors.affiliation: 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany [2].
authors.forename: Sandra
authors.initials: S
authors.lastname: Meier
authors.affiliation: 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.
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.affiliation: 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.
authors.forename: Per
authors.initials: P
authors.lastname: Hoffmann
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, D-53175 Bonn, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Lacour
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, D-97070 Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.affiliation: 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.
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.affiliation: Statistical Genetics, Department of Translational Psychiatry, Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lucae
authors.affiliation: Department of Psychiatry, University of Bonn, D-53127 Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.affiliation: Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwarz
authors.affiliation: Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Vedder
authors.affiliation: Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Kammerer-Ciernioch
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital, D-01307 Dresden, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pfennig
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital, D-01307 Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, D-72074 Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hautzinger
authors.affiliation: Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen, D-45147 Essen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.affiliation: 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.
authors.forename: Lutz
authors.initials: L
authors.lastname: Priebe
authors.affiliation: Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland.
authors.forename: Piotr M
authors.initials: PM
authors.lastname: Czerski
authors.affiliation: Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
authors.affiliation: Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw PL-02-781, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.affiliation: Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz PL-91-348, Poland.
authors.forename: Neonila
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.affiliation: Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.affiliation: 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.
authors.forename: Adam
authors.initials: A
authors.lastname: Wright
authors.affiliation: 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.
authors.forename: Philip B
authors.initials: PB
authors.lastname: Mitchell
authors.affiliation: 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.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Fullerton
authors.affiliation: 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.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.affiliation: Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.affiliation: Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Gordon
authors.affiliation: Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
authors.forename: Nicholas G
authors.initials: NG
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authors.affiliation: Moscow Research Institute of Psychiatry, Moscow 107258, Russian Federation.
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authors.initials: V
authors.lastname: Krasnow
authors.affiliation: Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation.
authors.forename: Alexander
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authors.lastname: Chuchalin
authors.affiliation: Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation.
authors.forename: Gulja
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authors.lastname: Babadjanova
authors.affiliation: Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
authors.forename: Galina
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authors.affiliation: Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
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authors.initials: LI
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authors.affiliation: Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
authors.forename: Alexander S
authors.initials: AS
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authors.affiliation: Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk 305041, Russian Federation.
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authors.affiliation: Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa 450054, Russian Federation.
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authors.affiliation: 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.
authors.forename: Martin
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authors.lastname: Alda
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authors.forename: Paul
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authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, Québec, Canada H3G 1A4.
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authors.initials: GA
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authors.affiliation: Department of Psychiatry, Douglas Hospital Research Institute, McGill University, Montreal, Quebec, Canada H4H 1R3.
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authors.initials: C
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authors.affiliation: Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain.
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authors.affiliation: Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain.
authors.forename: Fermin
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authors.affiliation: Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain.
authors.forename: Manolis
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authors.affiliation: Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest RO-041914, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Grigoroiu-Serbanescu
authors.affiliation: Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany.
authors.forename: Peter
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authors.lastname: Propping
authors.affiliation: 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.
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.affiliation: 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany [2].
authors.forename: Marcella
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authors.lastname: Rietschel
authors.affiliation: 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].
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: 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].
authors.forename: Sven
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authors.lastname: Cichon
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D000262:Adenylyl Cyclases; C100622:adenylyl cyclase 2