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Title: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
Author: Demontis, Ditte
Walters, Raymond
Rajagopal, Veera M.
Waldman, Irwin D.
Grove, Jakob
Als, Thomas D.
Dalsgaard, Soren
Ribasés Haro, Marta
Grauholm, Jonas
Bækvad-Hansen, Maria
Werge, Thomas
Nordentoft, Merete
Mors, Ole
Mortensen, Preben Bo
Psychiatric Genomics Consortium (PGC)
Cormand Rifà, Bru
Hougaard, David M.
Neale, Benjamin M.
Franke, Barbara
Faraone, Stephen V.
Børglum, Anders D.
Keywords: Trastorns per dèficit d'atenció amb hiperactivitat en els infants
Agressivitat en els infants
Attention deficit disorder with hyperactivity in children
Aggressiveness in children
Issue Date: 25-Jan-2021
Publisher: Nature Publishing Group
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.
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It is part of: Nature Communications, 2021, vol. 12, num. 1, p. 576
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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