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, Massachusetts General Hospital , Harvard Medical School, Broad Institute of Harvard and MIT
  • ,
  • Veera M. Rajagopal
  • Irwin D. Waldman, Emory University
  • ,
  • Jakob Grove
  • Thomas D. Als
  • Søren Dalsgaard
  • Marta Ribasas, Autonomous University of Barcelona, Instituto de Salud Carlos III, University of Barcelona, Hospital Universitari Vall d'Hebron
  • ,
  • Jonas Bybjerg-Grauholm, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Statens Serum Institut
  • ,
  • Maria Bækvad-Hansen, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Statens Serum Institut
  • ,
  • Thomas Werge, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Københavns Universitet, Mental Health Services Copenhagen
  • ,
  • Merete Nordentoft, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Københavns Universitet, Mental Health Center Copenhagen, Mental Health Services in the Capital Region of Denmark
  • ,
  • Ole Mors
  • Preben Bo Mortensen
  • ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
  • ,
  • Bru Cormand, Institut de Recerca Sant Joan de Déu, Universitat de Barcelona, Instituto de Salud Carlos III
  • ,
  • David M. Hougaard, Statens Serum Institut, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Danmark
  • Benjamin M Neale, Massachusetts General Hospital and Harvard Medical School, Broad Institute of Harvard and MIT
  • ,
  • Barbara Franke, Radboud University Nijmegen Medical Centre, Radboud University Medical Center, Danmark
  • Stephen V Faraone, SUNY Upstate Medical University, Danmark
  • Anders D. Børglum

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.

OriginalsprogEngelsk
Artikelnummer576
TidsskriftNature Communications
Vol/bind12
Nummer1
Antal sider12
ISSN2041-1723
DOI
StatusUdgivet - jan. 2021

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