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

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作者
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
机构
[1] Institute of Human Genetics,Department of Genomics
[2] University of Bonn,Department of Psychiatry and Psychotherapy
[3] Life & Brain Center,Department of Genetic Epidemiology in Psychiatry
[4] University of Bonn,Department of Biomedicine
[5] Institute of Neuroscience and Medicine (INM-1),Division of Medical Genetics, Department of Biomedicine
[6] Research Centre Jülich,Department of Psychiatry
[7] Institute for Medical Biometry,Department of Translational Psychiatry
[8] Informatics,Department of Psychiatry
[9] and Epidemiology,Department of Psychiatry and Psychotherapy
[10] University of Bonn,Department of Psychology
[11] German Center for Neurodegenerative Diseases (DZNE),Department of Psychiatry
[12] Bonn,Department of Cancer Epidemiology and Prevention
[13] Germany,Department of Epidemiology
[14] University of Go¨ttingen,Department of Biology
[15] Central Institute of Mental Health,Department of Psychiatry
[16] Medical Faculty Mannheim/Heidelberg University,Department of Psychiatry
[17] Aarhus University,Department of Neurology and Neurosurgery
[18] Institute for Genomic Mathematics,Department of Psychiatry
[19] University of Bonn,Département des sciences fondamentales
[20] University of Basel,Department of Psychiatry
[21] Psychosomatics and Psychotherapy,undefined
[22] University of Würzburg,undefined
[23] Statistical Genetics,undefined
[24] Max Planck Institute of Psychiatry,undefined
[25] Munich Cluster for Systems Neurology (SyNergy),undefined
[26] Institute of Translational Medicine,undefined
[27] University of Liverpool,undefined
[28] University of Bonn,undefined
[29] Psychiatric Center Nordbaden,undefined
[30] University Hospital,undefined
[31] Clinical Psychology and Psychotherapy,undefined
[32] Eberhard Karls University Tübingen,undefined
[33] Institute of Medical Informatics,undefined
[34] Biometry,undefined
[35] and Epidemiology,undefined
[36] University Duisburg-Essen,undefined
[37] Poznan University of Medical Sciences,undefined
[38] Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology,undefined
[39] Nofer Institute of Occupational Medicine,undefined
[40] Genetic Epidemiology Group,undefined
[41] International Agency for Research on Cancer (IARC),undefined
[42] Genetic Cancer Susceptibility Group,undefined
[43] International Agency for Research on Cancer (IARC),undefined
[44] School of Psychiatry,undefined
[45] University of New South Wales,undefined
[46] Black Dog Institute,undefined
[47] Prince of Wales Hospital,undefined
[48] Neuroscience Research Australia,undefined
[49] School of Medical Sciences,undefined
[50] Faculty of Medicine,undefined
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摘要
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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