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Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

Author

Listed:
  • Ditte Demontis

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

  • Raymond K. Walters

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Veera M. Rajagopal

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

  • Irwin D. Waldman

    (Emory University)

  • Jakob Grove

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

  • Thomas D. Als

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

  • Søren Dalsgaard

    (Aarhus University)

  • Marta Ribasés

    (Universitat Autònoma de Barcelona
    Hospital Universitari Vall d’Hebron
    Instituto de Salud Carlos III
    Universitat de Barcelona)

  • Jonas Bybjerg-Grauholm

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    Statens Serum Institut)

  • Maria Bækvad-Hansen

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    Statens Serum Institut)

  • Thomas Werge

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    University of Copenhagen
    Mental Health Services Copenhagen
    University of Copenhagen)

  • Merete Nordentoft

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    Mental Health Centre Copenhagen Mental Health Services in the Capital Region of Denmark
    University of Copenhagen)

  • Ole Mors

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    Aarhus University Hospital)

  • Preben Bo Mortensen

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

  • Bru Cormand

    (Universitat de Barcelona
    Instituto de Salud Carlos III
    Institut de Biomedicina de la Universitat de Barcelona (IBUB)
    Esplugues de Llobregat)

  • David M. Hougaard

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    Statens Serum Institut)

  • Benjamin M. Neale

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard
    Broad Institute of MIT and Harvard)

  • Barbara Franke

    (Radboud University Medical Center
    Radboud University Medical Center)

  • Stephen V. Faraone

    (SUNY Upstate Medical University)

  • Anders D. Børglum

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

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.

Suggested Citation

  • Ditte Demontis & Raymond K. Walters & Veera M. Rajagopal & Irwin D. Waldman & Jakob Grove & Thomas D. Als & Søren Dalsgaard & Marta Ribasés & Jonas Bybjerg-Grauholm & Maria Bækvad-Hansen & Thomas Werg, 2021. "Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20443-2
    DOI: 10.1038/s41467-020-20443-2
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