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

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 signific...

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Detalhes bibliográficos
Autores: 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.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/173506
Acesso em linha:https://hdl.handle.net/2445/173506
Access Level:acceso abierto
Palavra-chave:Trastorns per dèficit d'atenció amb hiperactivitat en els infants
Agressivitat en els infants
Attention deficit disorder with hyperactivity in children
Aggressiveness in children
Descrição
Resumo: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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