Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24618891
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.
DATE PUBLISHED
2014
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/08/14
accepted 2014/01/29
entrez 2014/03/13 06:00
pubmed 2014/03/13 06:00
medline 2015/11/03 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Mühleisen TW Mühleisen Thomas W TW 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].
Leber M Leber Markus M 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].
Schulze TG Schulze Thomas G TG 1] Department of Psychiatry and Psychotherapy, University of Go¨ttingen, D-37075 Göttingen, Germany [2].
Strohmaier J Strohmaier Jana J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
Degenhardt F Degenhardt Franziska F 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.
Treutlein J Treutlein Jens J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
Mattheisen M Mattheisen Manuel M 1] Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark [2] Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany.
Forstner AJ Forstner Andreas J AJ 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.
Schumacher J Schumacher Johannes J 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.
Breuer R Breuer René R Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
Meier S Meier Sandra S 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany [2].
Herms S Herms Stefan S 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.
Hoffmann P Hoffmann Per P 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.
Lacour A Lacour André A German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, D-53175 Bonn, Germany.
Witt SH Witt Stephanie H SH Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany.
Reif A Reif Andreas A Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, D-97070 Würzburg, Germany.
Müller-Myhsok B Müller-Myhsok Bertram B 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.
Lucae S Lucae Susanne S Statistical Genetics, Department of Translational Psychiatry, Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
Maier W Maier Wolfgang W Department of Psychiatry, University of Bonn, D-53127 Bonn, Germany.
Schwarz M Schwarz Markus M Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
Vedder H Vedder Helmut H Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
Kammerer-Ciernioch J Kammerer-Ciernioch Jutta J Psychiatric Center Nordbaden, D-69168 Wiesloch, Germany.
Pfennig A Pfennig Andrea A Department of Psychiatry and Psychotherapy, University Hospital, D-01307 Dresden, Germany.
Bauer M Bauer Michael M Department of Psychiatry and Psychotherapy, University Hospital, D-01307 Dresden, Germany.
Hautzinger M Hautzinger Martin M Department of Psychology, Clinical Psychology and Psychotherapy, Eberhard Karls University Tübingen, D-72074 Tübingen, Germany.
Moebus S Moebus Susanne S Institute of Medical Informatics, Biometry, and Epidemiology, University Duisburg-Essen, D-45147 Essen, Germany.
Priebe L Priebe Lutz L 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.
Czerski PM Czerski Piotr M PM Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland.
Hauser J Hauser Joanna J Department of Psychiatry, Poznan University of Medical Sciences, Poznan PL-60-572, Poland.
Lissowska J Lissowska Jolanta J Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw PL-02-781, Poland.
Szeszenia-Dabrowska N Szeszenia-Dabrowska Neonila N Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz PL-91-348, Poland.
Brennan P Brennan Paul P Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
McKay JD McKay James D JD Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), 69372 Lyon CEDEX 08, France.
Wright A Wright Adam A 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.
Mitchell PB Mitchell Philip B PB 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.
Fullerton JM Fullerton Janice M JM 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.
Schofield PR Schofield Peter R PR 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.
Montgomery GW Montgomery Grant W GW Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
Medland SE Medland Sarah E SE Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
Gordon SD Gordon Scott D SD Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
Martin NG Martin Nicholas G NG Queensland Institute of Medical Research (QIMR), Brisbane, Queensland 4006, Australia.
Krasnow V Krasnow Valery V Moscow Research Institute of Psychiatry, Moscow 107258, Russian Federation.
Chuchalin A Chuchalin Alexander A Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation.
Babadjanova G Babadjanova Gulja G Institute of Pulmonology, Russian State Medical University, Moscow 105077, Russian Federation.
Pantelejeva G Pantelejeva Galina G Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
Abramova LI Abramova Lilia I LI Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
Tiganov AS Tiganov Alexander S AS Russian Academy of Medical Sciences, Mental Health Research Center, Moscow 115522, Russian Federation.
Polonikov A Polonikov Alexey A Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk 305041, Russian Federation.
Khusnutdinova E Khusnutdinova Elza E Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa 450054, Russian Federation.
Alda M Alda Martin M 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.
Grof P Grof Paul P 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.
Rouleau GA Rouleau Guy A GA Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, Québec, Canada H3G 1A4.
Turecki G Turecki Gustavo G Department of Psychiatry, Douglas Hospital Research Institute, McGill University, Montreal, Quebec, Canada H4H 1R3.
Laprise C Laprise Catherine C Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, Canada G7H 2B1.
Rivas F Rivas Fabio F Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain.
Mayoral F Mayoral Fermin F Department of Psychiatry, Hospital Regional Universitario Carlos Haya, Malaga 29009, Spain.
Kogevinas M Kogevinas Manolis M Center for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain.
Grigoroiu-Serbanescu M Grigoroiu-Serbanescu Maria M Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest RO-041914, Romania.
Propping P Propping Peter P Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany.
Becker T Becker Tim T 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.
Rietschel M Rietschel Marcella M 1] Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, D-68159 Mannheim, Germany [2].
Nöthen MM Nöthen Markus M MM 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].
Cichon S Cichon Sven S 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].
INVESTIGATORS
JOURNAL
VOLUME: 5
ISSUE:
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2014
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
084703 Wellcome Trust United Kingdom
64410 Canadian Institutes of Health Research Canada
MOP-13506 Canadian Institutes of Health Research Canada
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adenylyl Cyclases genetics
Bipolar Disorder genetics
Female genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study methods
Humans methods
Male methods
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 4.6.1.1 Adenylyl Cyclases
EC 4.6.1.1 adenylyl cyclase 2
OTHER ID's