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Identification of Genetic Loci Shared Between Attention-Deficit/Hyperactivity Disorder, Intelligence, and Educational Attainment

  • Kevin S. O’Connell
    Correspondence
    Address correspondence to Kevin S. O’Connell, Ph.D., or Ole A. Andreassen, M.D., Ph.D., Division of Mental Health and Addiction, Oslo University Hospital, Kirkeveien 166, 0424 Oslo, Norway.
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • Alexey Shadrin
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • Olav B. Smeland
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • Shahram Bahrami
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • Oleksandr Frei
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • Francesco Bettella
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • Florian Krull
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • Chun C. Fan
    Affiliations
    Department of Radiology, University of California, San Diego, La Jolla, California

    Department of Cognitive Science, University of California, San Diego, La Jolla, California
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  • Ragna B. Askeland
    Affiliations
    Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway
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  • Gun Peggy S. Knudsen
    Affiliations
    Division of Health Data and Digitalisation, Norwegian Institute of Public Health, Oslo, Norway
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  • Anne Halmøy
    Affiliations
    Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
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  • Nils Eiel Steen
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • Torill Ueland
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Department of Psychology, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
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  • G. Bragi Walters
    Affiliations
    deCODE Genetics/Amgen, Reykjavik, Iceland

    Faculty of Medicine, University of Iceland, Reykjavik, Iceland
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  • Katrín Davíðsdóttir
    Affiliations
    The Centre for Child Development and Behaviour, Capital Area Primary Health Care, Reykjavik, Iceland
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  • Gyða S. Haraldsdóttir
    Affiliations
    The Centre for Child Development and Behaviour, Capital Area Primary Health Care, Reykjavik, Iceland
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  • Ólafur Ó. Guðmundsson
    Affiliations
    deCODE Genetics/Amgen, Reykjavik, Iceland

    Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    Department of Child and Adolescent Psychiatry, National University Hospital, Reykjavik, Iceland
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  • Hreinn Stefánsson
    Affiliations
    deCODE Genetics/Amgen, Reykjavik, Iceland
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  • Ted Reichborn-Kjennerud
    Affiliations
    Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway
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  • Jan Haavik
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway

    Department of Biomedicine, University of Bergen, Bergen, Norway

    Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
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  • Anders M. Dale
    Affiliations
    Department of Radiology, University of California, San Diego, La Jolla, California

    Department of Psychiatry, University of California, San Diego, La Jolla, California

    Department of Neurosciences, University of California, San Diego, La Jolla, California

    Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California
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  • Kári Stefánsson
    Affiliations
    deCODE Genetics/Amgen, Reykjavik, Iceland

    Faculty of Medicine, University of Iceland, Reykjavik, Iceland
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  • Srdjan Djurovic
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway

    Department of Medical Genetics, Oslo University Hospital, Oslo, Norway

    Department of Clinical Science, University of Bergen, Bergen, Norway
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  • Ole A. Andreassen
    Correspondence
    Address correspondence to Kevin S. O’Connell, Ph.D., or Ole A. Andreassen, M.D., Ph.D., Division of Mental Health and Addiction, Oslo University Hospital, Kirkeveien 166, 0424 Oslo, Norway.
    Affiliations
    Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
    Search for articles by this author
Published:November 28, 2019DOI:https://doi.org/10.1016/j.biopsych.2019.11.015

      Abstract

      Background

      Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown.

      Methods

      We analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment (N = 842,499), and general intelligence (N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes.

      Results

      We identified 58 linkage disequilibrium–independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD.

      Conclusions

      These results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence.

      Keywords

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