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Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy

Author

Listed:
  • Guy Hindley

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
    Psychology and Neurosciences, King’s College London)

  • Alexey A. Shadrin

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
    University of Oslo)

  • Dennis Meer

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
    Maastricht University)

  • Nadine Parker

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital)

  • Weiqiu Cheng

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital)

  • Kevin S. O’Connell

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital)

  • Shahram Bahrami

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital)

  • Aihua Lin

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital)

  • Naz Karadag

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital)

  • Børge Holen

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital)

  • Thomas Bjella

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
    Oslo University Hospital)

  • Ian J. Deary

    (University of Edinburgh)

  • Gail Davies

    (University of Edinburgh)

  • W. David Hill

    (University of Edinburgh)

  • Jan Bressler

    (University of Texas Health Science Center at Houston)

  • Sudha Seshadri

    (University of Texas Health Sciences Center
    Framingham Heart Study
    Boston University School of Medicine)

  • Chun Chieh Fan

    (University of California San Diego
    Laureate Institute for Brain Research)

  • Torill Ueland

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
    University of Oslo)

  • Srdjan Djurovic

    (University of Oslo
    Oslo University Hospital
    University of Bergen)

  • Olav B. Smeland

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital)

  • Oleksandr Frei

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
    University of Oslo)

  • Anders M. Dale

    (University of California San Diego
    University of California, San Diego
    University of California San Diego
    University of California, San Diego)

  • Ole A. Andreassen

    (University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
    University of Oslo)

Abstract

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the ‘pleiotropy-informed’ multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function.

Suggested Citation

  • Guy Hindley & Alexey A. Shadrin & Dennis Meer & Nadine Parker & Weiqiu Cheng & Kevin S. O’Connell & Shahram Bahrami & Aihua Lin & Naz Karadag & Børge Holen & Thomas Bjella & Ian J. Deary & Gail Davies, 2023. "Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy," Nature Human Behaviour, Nature, vol. 7(9), pages 1584-1600, September.
    • Handle: RePEc:nat:nathum:v:7:y:2023:i:9:d:10.1038_s41562-023-01630-9
    DOI: 10.1038/s41562-023-01630-9
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