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A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment

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

  • Andrew J Schork, Mental Health Center Sct. Hans, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
  • ,
  • Hyejung Won, University of California, University of North Carolina
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  • Vivek Appadurai, Mental Health Center Sct. Hans, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
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  • Ron Nudel, Mental Health Center Sct. Hans, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
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  • Mike Gandal, University of California
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  • Olivier Delaneau, University of Geneva
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  • Malene Revsbech Christiansen, Technical University of Denmark,
  • David M Hougaard, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark., Statens Serum Institut
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  • Marie Bækved-Hansen, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark., Statens Serum Institut
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  • Jonas Bybjerg-Grauholm, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark., Statens Serum Institut
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  • Marianne Giørtz Pedersen
  • Esben Agerbo
  • Carsten Bøcker Pedersen
  • Benjamin M Neale, Massachusetts General Hospital and Harvard Medical School, Broad Institute of Harvard and MIT
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  • Mark J Daly, Massachusetts General Hospital and Harvard Medical School, Broad Institute of Harvard and MIT
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  • Naomi R Wray, University of Queensland
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  • Merete Nordentoft, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark., Mental Health Services Capital Region of Denmark, University of Copenhagen
  • ,
  • Ole Mors
  • Anders D Børglum
  • Preben Bo Mortensen
  • Alfonso Buil, Mental Health Center Sct. Hans, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
  • ,
  • Wesley K Thompson, Mental Health Center Sct. Hans, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark., University of California
  • ,
  • Daniel H Geschwind, University of California
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  • Thomas Werge, Mental Health Center Sct. Hans, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark., University of Copenhagen

There is mounting evidence that seemingly diverse psychiatric disorders share genetic etiology, but the biological substrates mediating this overlap are not well characterized. Here we leverage the unique Integrative Psychiatric Research Consortium (iPSYCH) study, a nationally representative cohort ascertained through clinical psychiatric diagnoses indicated in Danish national health registers. We confirm previous reports of individual and cross-disorder single-nucleotide polymorphism heritability for major psychiatric disorders and perform a cross-disorder genome-wide association study. We identify four novel genome-wide significant loci encompassing variants predicted to regulate genes expressed in radial glia and interneurons in the developing neocortex during mid-gestation. This epoch is supported by partitioning cross-disorder single-nucleotide polymorphism heritability, which is enriched at regulatory chromatin active during fetal neurodevelopment. These findings suggest that dysregulation of genes that direct neurodevelopment by common genetic variants may result in general liability for many later psychiatric outcomes.

Original languageEnglish
JournalNature Neuroscience
Volume22
Issue3
Pages (from-to)353-361
Number of pages9
ISSN1097-6256
DOIs
Publication statusPublished - Mar 2019

    Research areas

  • AUTISM SPECTRUM DISORDER, BIPOLAR DISORDER, CHILDHOOD, FAMILY-HISTORY, HERITABILITY, HUMAN-DISEASES, IDENTIFICATION, LOCI, METAANALYSIS, SCHIZOPHRENIA, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Risk Factors, Gene Expression Regulation, Male, Genetic Loci, Mental Disorders/genetics, Brain/embryology, Female, Polymorphism, Single Nucleotide, Cohort Studies

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