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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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DOI

  • Niamh Mullins, Icahn School of Medicine at Mount Sinai
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  • Andreas J Forstner, University of Bonn
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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, University of Queensland
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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, Icahn School of Medicine at Mount Sinai
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  • Ole Kristian Drange, Norwegian University of Science and Technology
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  • Michael J Gandal, University of California at San Diego
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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, University of California at San Diego
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  • Kristi Krebs, University of Tartu
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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, Icahn School of Medicine at Mount Sinai
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  • Laura G Sloofman, Icahn School of Medicine at Mount Sinai
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  • Stacy Steinberg, deCODE Genetics
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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
    • ,
  • Esben Agerbo
  • Mariam Al Eissa, University College London
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  • Diego Albani, Department of Molecular Neuroscience
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  • Ney Alliey-Rodriguez, University of Chicago
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  • Adebayo Anjorin, Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, London
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  • Verneri Antilla, Massachusetts General Hospital
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  • Anastasia Antoniou, 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 -The Lundbeck Foundation Initiative for Integrative Psychiatric Research
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  • Nicholas Bass, University College London
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  • Michael Bauer, Technische Universität Dresden
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  • Eva C Beins, University of Bonn
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  • Sarah E Bergen, Karolinska Institutet
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  • Armin Birner, Medical University of Graz
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  • Carsten Bøcker Pedersen
  • Marianne Giørtz Pedersen
  • Jakob Grove
  • Manuel Mattheisen, iSEQ - Centre for Integrative Sequencing, iPSYCH -The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 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.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind53
Nummer6
Sider (fra-til)817-829
Antal sider13
ISSN1061-4036
DOI
StatusUdgivet - jun. 2021

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