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

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  • 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 Werge
  • Merete Nordentoft
  • Ole Mors
  • Preben Bo Mortensen
  • ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
  • Bru Cormand
  • David M Hougaard
  • Benjamin M Neale
  • Barbara Franke
  • Stephen V Faraone
  • Anders D Børglum
  • Hans-Christoph Steinhausen (Member of study group)
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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 (h 2 SNP = 0.34) when compared to ADHD without DBDs (h 2 SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (r g = 0.81) and anti-social behaviors (r g = 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.

Original languageEnglish
Article number576
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

    Research areas

  • Attention Deficit Disorder with Hyperactivity/epidemiology, Attention Deficit and Disruptive Behavior Disorders/epidemiology, Child, China/epidemiology, Cohort Studies, Comorbidity, Europe/epidemiology, Female, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study/methods, Humans, Male, Multifactorial Inheritance/genetics, Polymorphism, Single Nucleotide, Risk Factors

ID: 63734511