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Genome-wide association study identifies 30 loci associated with bipolar disorder

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

  • Eli A Stahl, Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. eli.stahl@mssm.edu., Icahn School of Medicine at Mount Sinai
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  • Gerome Breen, King’s College London
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  • Andreas J Forstner, Institute of Medical Genetics and Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland., University of Basel, Institute of Human Genetics, School of Medicine & University Hospital Bonn, University of Bonn, Bonn 53127, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn 53127, Germany., University of Marburg
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  • Andrew McQuillin, Division of Psychiatry, University College London, London, UK, claudia.cooper@ucl.ac.uk.
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  • Stephan Ripke, Analytic and Translational Genetics Unit, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA., Broad Institute, Charité-Universitätsmedizin, Berlin
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  • Vassily Trubetskoy, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin, Germany.
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  • Manuel Mattheisen
  • Yunpeng Wang, Mental Health Centre, Sct. Hans, Copenhagen University Hospital, University of Oslo, Oslo
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  • Jonathan R I Coleman, NIHR BRC for Mental Health, King's College London, London, Great Britain.
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  • Héléna A Gaspar, NIHR BRC for Mental Health, King's College London, London, Great Britain.
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  • Christiaan A de Leeuw, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
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  • Stacy Steinberg, deCODE Genetics/Amgen inc., Reykjavik, 101, Iceland.
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  • Jennifer M Whitehead Pavlides, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
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  • Maciej Trzaskowski, The University of Queensland
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  • Enda M Byrne, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
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  • Tune H Pers, Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA., Broad Institute
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  • Peter A Holmans, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, England.
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  • Alexander L Richards, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, England.
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  • Liam Abbott, Broad Institute
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  • Esben Agerbo
  • Huda Akil, Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
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  • Diego Albani, Department of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
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  • Ney Alliey-Rodriguez, Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
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  • Thomas D Als
  • Adebayo Anjorin, Department of Psychiatry, Berkshire Healthcare NHS Foundation Trust, Bracknell, UK.
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  • Verneri Antilla, Analytic and Translational Genetics Unit, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
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  • Swapnil Awasthi, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin, Germany.
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  • Judith A Badner, Department of Psychiatry, Rush University Medical Center, Chicago, IL, USA.
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  • Marie Bækvad-Hansen, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark., iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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  • Jack D Barchas, Department of Psychiatry, Weill Cornell Medical College, New York City, NY, USA.
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  • Nicholas Bass, Division of Psychiatry, University College London, London, UK, claudia.cooper@ucl.ac.uk.
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  • Michael Bauer, Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany.
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  • Richard Belliveau, Broad Institute
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  • Sarah E Bergen, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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  • Carsten Bøcker Pedersen
  • Erlend Bøen, Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
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  • Marco P Boks, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht, the Netherlands.
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  • James Boocock, Human Genetics and Biostatistics, University of California Los Angeles, Los Angeles, CA 90095-7088, USA.
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  • Monika Budde, Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich, Nussbaumstr. 7, Munich 80336, Germany.
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  • William Bunney, Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
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  • Margit Burmeister, Molecular & Behavioral Neuroscience Institute and Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
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  • Jonas Bybjerg-Grauholm, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark., iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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  • William Byerley, Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
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  • Marianne Giørtz Pedersen
  • Jakob Grove
  • Wei Xu, Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Onatario, Canada., Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
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  • Peng Zhang
  • Anders D Børglum
  • Ole Mors
  • Preben Bo Mortensen
  • eQTLGen Consortium

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

Original languageEnglish
JournalNature Genetics
Volume51
Issue5
Pages (from-to)793-803
Number of pages11
ISSN1061-4036
DOIs
Publication statusPublished - May 2019

    Research areas

  • GENES, GWAS, HERITABILITY, INDIVIDUALS, LD SCORE REGRESSION, METAANALYSIS, POLYGENICITY, RISK, SCHIZOPHRENIA, VARIANTS

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