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

Ditte Demontis*, Raymond K. Walters, Veera M. Rajagopal, Irwin D. Waldman, Jakob Grove, Thomas D. Als, Søren Dalsgaard, Marta Ribasas, 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 FaraoneAnders D. Børglum*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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.

Original languageEnglish
Article number576
JournalNature Communications
Volume12
Issue1
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - Jan 2021

Keywords

  • 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

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