Department of Economics and Business Economics

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

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

  • Niamh Mullins, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of
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  • Andreas J Forstner, 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.
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  • Kevin S O'Connell, University of Oslo
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  • Brandon Coombes, Department of Health Sciences Research, Mayo Clinic.
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  • Jonathan R I Coleman, King's College London
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  • Zhen Qiao, The University of Queensland Diamantina Institute, University of Queensland, Australia.
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  • Thomas D Als
  • Tim B Bigdeli, SUNY Downstate Health Sciences University
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  • Sigrid Børte, University of Oslo
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  • Julien Bryois, Karolinska Institutet
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  • Alexander W Charney, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of
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  • Ole Kristian Drange, Norwegian University of Science and Technology
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  • Michael J Gandal, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
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  • Saskia P Hagenaars, King's College London
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  • Masashi Ikeda, Fujita Hlth Univ, Fujita Health University, Sch Med, Dept Psychiat
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  • Nolan Kamitaki, Broad Inst MIT & Harvard, Broad Institute, Harvard University, Massachusetts Institute of Technology (MIT), Stanley Ctr Psychiat Res
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  • Minsoo Kim, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
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  • Kristi Krebs, Tartu University Hospital, Children's Clinic, Tartu, Estonia; Department of Paediatrics, University of Tartu, Tartu, Estonia.
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  • Georgia Panagiotaropoulou, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Frankfurt, Frankfurt, Germany.
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  • Brian M Schilder, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of
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  • Laura G Sloofman, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of
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  • Stacy Steinberg, DeCODE Genetics/Amgen
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  • Vassily Trubetskoy, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Frankfurt, Frankfurt, Germany.
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  • Bendik S Winsvold, Norwegian University of Science and Technology
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  • Hong-Hee Won, Sungkyunkwan University
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  • Liliya Abramova, Russian Academy of Medical Sciences
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  • Kristina Adorjan, From the Danish Multiple Sclerosis Center (M.D.B., T.A.C., F.S., P.S.S., M.M.), Rigshospitalet; Copenhagen University Hospital Rigshospitalet (J.F., H.H.-K.-R.), Glostrup; Slagelse Hospital (M.K.G.); Odense University Hospital (Z.I., T.S.), University of Southern Denmark; Hospital of Southern Jutland (M.K.), Sønderborg; Aalborg University Hospital (Z.M.); Aarhus University Hospital (T.P., P.V.R.); Greater Copenhagen Hospitals-NOH (H.R.), Hillerød; University Hospital of Sjaelland (A.T.), Roskilde; and Depar
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  • Esben Agerbo
  • Mariam Al Eissa, London Ctr Nanotechnol, University College London, University of London
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  • Diego Albani, Department of Molecular Neuroscience
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  • Ney Alliey-Rodriguez, University of Chicago, Chicago, Illinois.
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  • Adebayo Anjorin, Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, London
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  • Verneri Antilla, Massachusetts General Hospital, Boston, Massachusetts, USA.
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  • Anastasia Antoniou, National and Kapodistrian University of Athens
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  • Swapnil Awasthi, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Frankfurt, Frankfurt, Germany.
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  • Ji Hyun Baek, Sungkyunkwan University
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  • Marie Bækvad-Hansen, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Lundbeck Fdn Initiat Integrat Psychiat Res
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  • Nicholas Bass, London Ctr Nanotechnol, University College London, University of London
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  • Michael Bauer, Tech Univ Dresden, CARL GUSTAV CARUS UNIVERSITY HOSPITAL, Dresden University of Technology, Univ Hosp Carl Gustav Carus, Dept Gynaecol & Obstet
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  • Eva C Beins, 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.
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  • Sarah E Bergen, Karolinska Institutet
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  • Armin Birner, Cancer Biology Unit, Department of Dermatology, Medical University of Graz, Graz, Austria; Center for Medical Research, Medical University of Graz, Graz, Austria.
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  • Carsten Bøcker Pedersen
  • Marianne Giørtz Pedersen
  • Jakob Grove
  • Manuel Mattheisen, iSEQ - Centre for Integrative Sequencing, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Lundbeck Fdn Initiat Integrat Psychiat Res, Karolinska Institutet, University of Würzburg
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  • Wei Xu, Dalla Lana School of Public Health, University of Toronto, Ontario Cancer Institute, Princess Margaret Cancer Center, Toronto, Ontario, Canada.
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  • Anders D Børglum
  • Ole Mors
  • Preben Bo Mortensen
  • HUNT All-In Psychiatry

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Original languageEnglish
JournalNature Genetics
Volume53
Issue6
Pages (from-to)817-829
Number of pages13
ISSN1061-4036
DOIs
Publication statusPublished - Jun 2021

    Research areas

  • Bipolar Disorder/genetics, Case-Control Studies, Chromosomes, Human/genetics, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Major Histocompatibility Complex/genetics, Multifactorial Inheritance/genetics, Phenotype, Quantitative Trait Loci/genetics, Risk Factors

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