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

Research output: Contribution to journalJournal articleResearchpeer-review

  • 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
  • Werge, Thomas
  • Nordentoft, Merete
  • Ole Mors
  • Preben Bo Mortensen
  • Ole A. Andreassen
  • Maria Jesús Arranz
  • Tobias Banaschewski
  • Claiton Bau
  • Mark Bellgrove
  • Joseph Biederman
  • Isabell Brikell
  • Jan K. Buitelaar
  • Christie L. Burton
  • Miguel Casas
  • Jennifer Crosbie
  • Alysa E. Doyle
  • Richard P. Ebstein
  • Josephine Elia
  • Corfield C. Elizabeth
  • Eugenio Grevet
  • Natalie Grizenko
  • Alexandra Havdahl
  • Ziarih Hawi
  • Johannes Hebebrand
  • Amaia Hervas
  • Sarah Hohmann
  • Jan Haavik
  • Ridha Joober
  • Lindsey Kent
  • Jonna Kuntsi
  • Kate Langley
  • Larsson, Henrik Bo Wiberg
  • Klaus Peter Lesch
  • Patrick W.L. Leung
  • Calwing Liao
  • Sandra K. Loo
  • Joanna Martin
  • Nicholas G. Martin
  • Sarah E. Medland
  • Ana Miranda
  • ADHD Working Group of the Psychiatric Genomics Consortium (PGC)

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
ISSN2041-1723
DOIs
Publication statusPublished - 2021

Bibliographical note

Author Correction. DOI: 10.1038/s41467-020-20443-2

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