Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
Demontis, Ditte (Aarhus University)
Walters, Raymond K. (Broad Institute of MIT and Harvard.)
Rajagopal, Veera M. (Aarhus University)
Waldman, Irwin D. (Emory University)
Grove, Jakob (Aarhus University)
Als, Thomas D. (Aarhus University)
Dalsgaard, Søren (Aarhus University)
Ribasés Haro, Marta (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Bybjerg-Grauholm, Jonas (Statens Serum Institut)
Bækvad-Hansen, Marie (Statens Serum Institut)
Werge, Thomas (University of Copenhagen)
Nordentoft, Merete (University of Copenhagen Medicine)
Mors, Ole (Aarhus University Hospital (Aarhus, Dinamarca))
Mortensen, Preben Bo (Aarhus University)
Cormand, Bru (Institut de Recerca Sant Joan de Déu)
Hougaard, David M. (Statens Serum Institut)
Neale, Benjamin M. (Broad Institute of MIT and Harvard)
Franke, Barbara (Radboud University Medical Center)
Faraone, Stephen V. (SUNY Upstate Medical University)
Børglum, Anders D. (Aarhus University)

Date:	2021
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 (h 2 = 0. 34) when compared to ADHD without DBDs (h 2 = 0. 20), high genetic correlations between ADHD + DBDs and aggressive (r = 0. 81) and anti-social behaviors (r = 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. ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.
Grants:	European Commission. Horizon 2020 667302 European Commission 602805
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Genome-wide association studies ; ADHD
Published in:	Nature communications, Vol. 12 (january 2021) , ISSN 2041-1723

DOI: 10.1038/s41467-020-20443-2
PMID: 33495439

12 p, 1.0 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles