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Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy

Author

Listed:
  • Ellen Verhoef

    (Max Planck Institute for Psycholinguistics
    International Max Planck Research School for Language Sciences)

  • Jakob Grove

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    iSEQ, Aarhus University
    Center for Genomics and Personalized Medicine
    Aarhus University)

  • Chin Yang Shapland

    (University of Bristol
    University of Bristol)

  • Ditte Demontis

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    iSEQ, Aarhus University
    Center for Genomics and Personalized Medicine)

  • Stephen Burgess

    (University of Cambridge
    University of Cambridge)

  • Dheeraj Rai

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

  • Anders D. Børglum

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    iSEQ, Aarhus University
    Center for Genomics and Personalized Medicine)

  • Beate St Pourcain

    (Max Planck Institute for Psycholinguistics
    University of Bristol
    Radboud University)

Abstract

Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex co-occurring neurodevelopmental conditions. Their genetic architectures reveal striking similarities but also differences, including strong, discordant polygenic associations with educational attainment (EA). To study genetic mechanisms that present as ASD-related positive and ADHD-related negative genetic correlations with EA, we carry out multivariable regression analyses using genome-wide summary statistics (N = 10,610–766,345). Our results show that EA-related genetic variation is shared across ASD and ADHD architectures, involving identical marker alleles. However, the polygenic association profile with EA, across shared marker alleles, is discordant for ASD versus ADHD risk, indicating independent effects. At the single-variant level, our results suggest either biological pleiotropy or co-localisation of different risk variants, implicating MIR19A/19B microRNA mechanisms. At the polygenic level, they point to a polygenic form of pleiotropy that contributes to the detectable genome-wide correlation between ASD and ADHD and is consistent with effect cancellation across EA-related regions.

Suggested Citation

  • Ellen Verhoef & Jakob Grove & Chin Yang Shapland & Ditte Demontis & Stephen Burgess & Dheeraj Rai & Anders D. Børglum & Beate St Pourcain, 2021. "Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26755-1
    DOI: 10.1038/s41467-021-26755-1
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    References listed on IDEAS

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