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Brain Structure and Function Show Distinct Relations With Genetic Predispositions to Mental Health and Cognition

  • Shu Liu
    Correspondence
    Address correspondence to Shu Liu, M.Sc.
    Affiliations
    Amsterdam Neuroscience, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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  • Dirk J.A. Smit
    Affiliations
    Amsterdam Neuroscience, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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  • Author Footnotes
    1 AA, GAvW, and KJHV contributed equally to this work as joint supervisors.
    Abdel Abdellaoui
    Footnotes
    1 AA, GAvW, and KJHV contributed equally to this work as joint supervisors.
    Affiliations
    Amsterdam Neuroscience, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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  • Author Footnotes
    1 AA, GAvW, and KJHV contributed equally to this work as joint supervisors.
    Guido A. van Wingen
    Correspondence
    Guido A. van Wingen, Ph.D.
    Footnotes
    1 AA, GAvW, and KJHV contributed equally to this work as joint supervisors.
    Affiliations
    Amsterdam Neuroscience, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
    Search for articles by this author
  • Author Footnotes
    1 AA, GAvW, and KJHV contributed equally to this work as joint supervisors.
    Karin J.H. Verweij
    Footnotes
    1 AA, GAvW, and KJHV contributed equally to this work as joint supervisors.
    Affiliations
    Amsterdam Neuroscience, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
    Search for articles by this author
  • Author Footnotes
    1 AA, GAvW, and KJHV contributed equally to this work as joint supervisors.
Open AccessPublished:August 09, 2022DOI:https://doi.org/10.1016/j.bpsc.2022.08.003

      Abstract

      Background

      Mental health and cognitive achievement are partly heritable, highly polygenic, and associated with brain variations in structure and function. However, the underlying neural mechanisms remain unclear.

      Methods

      We investigated the association between genetic predispositions to various mental health and cognitive traits and a large set of structural and functional brain measures from the UK Biobank (N = 36,799). We also applied linkage disequilibrium score regression to estimate the genetic correlations between various traits and brain measures based on genome-wide data. To decompose the complex association patterns, we performed a multivariate partial least squares model of the genetic and imaging modalities.

      Results

      The univariate analyses showed that certain traits were related to brain structure (significant genetic correlations with total cortical surface area from  r g = −0.101 for smoking initiation to r g  = 0.230 for cognitive ability), while other traits were related to brain function (significant genetic correlations with functional connectivity from r g  = −0.161 for educational attainment to r g  = 0.318 for schizophrenia). The multivariate analysis showed that genetic predispositions to attention-deficit/hyperactivity disorder, smoking initiation, and cognitive traits had stronger associations with brain structure than with brain function, whereas genetic predispositions to most other psychiatric disorders had stronger associations with brain function than with brain structure.

      Conclusions

      These results reveal that genetic predispositions to mental health and cognitive traits have distinct brain profiles.

      Keywords

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