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Structural models of genome-wide covariance identify multiple common dimensions in autism

Author

Listed:
  • Lucía de Hoyos

    (Max Planck Institute for Psycholinguistics)

  • Maria T. Barendse

    (Max Planck Institute for Psycholinguistics
    Academic Centre for Dentistry Amsterdam (ACTA))

  • Fenja Schlag

    (Max Planck Institute for Psycholinguistics)

  • Marjolein M. J. van Donkelaar

    (Max Planck Institute for Psycholinguistics)

  • Ellen Verhoef

    (Max Planck Institute for Psycholinguistics)

  • Chin Yang Shapland

    (MRC Integrative Epidemiology Unit, University of Bristol
    University of Bristol)

  • Alexander Klassmann

    (University of Cologne)

  • Jan Buitelaar

    (Cognition and Behaviour, Radboud University
    Karakter Child and Adolescent Psychiatry University Centre
    Radboud University Medical Center)

  • Brad Verhulst

    (Texas A&M University)

  • Simon E. Fisher

    (Max Planck Institute for Psycholinguistics
    Cognition and Behaviour, Radboud University)

  • Dheeraj Rai

    (University of Bristol
    Avon and Wiltshire Partnership NHS Mental Health Trust
    University of Bristol)

  • Beate St Pourcain

    (Max Planck Institute for Psycholinguistics
    MRC Integrative Epidemiology Unit, University of Bristol
    Cognition and Behaviour, Radboud University)

Abstract

Common genetic variation has been associated with multiple phenotypic features in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous phenotypic spectrum is limited. Here, we developed and implemented a structural equation modelling framework to directly model genomic covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent with a case-only design. We identified three independent genetic factors most strongly linked to language performance, behaviour and developmental motor delay, respectively, studying an autism community sample (N = 5331). The three-factorial structure was largely confirmed in independent ASD-simplex families (N = 1946), although we uncovered, in addition, simplex-specific genetic overlap between behaviour and language phenotypes. Multivariate models across cohorts revealed novel associations, including links between language and early mastering of self-feeding. Thus, the common genetic architecture in ASD is multi-dimensional with overarching genetic factors contributing, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.

Suggested Citation

  • Lucía de Hoyos & Maria T. Barendse & Fenja Schlag & Marjolein M. J. van Donkelaar & Ellen Verhoef & Chin Yang Shapland & Alexander Klassmann & Jan Buitelaar & Brad Verhulst & Simon E. Fisher & Dheeraj, 2024. "Structural models of genome-wide covariance identify multiple common dimensions in autism," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46128-8
    DOI: 10.1038/s41467-024-46128-8
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    References listed on IDEAS

    as
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