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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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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/173506
Acceso en línea:https://hdl.handle.net/2445/173506
Access Level:acceso abierto
Palabra clave:Trastorns per dèficit d'atenció amb hiperactivitat en els infants
Agressivitat en els infants
Attention deficit disorder with hyperactivity in children
Aggressiveness in children
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repository_id_str
spelling Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorderDemontis, DitteWalters, RaymondRajagopal, Veera M.Waldman, Irwin D.Grove, JakobAls, Thomas D.Dalsgaard, SorenRibasés Haro, MartaGrauholm, JonasBækvad-Hansen, MariaWerge, ThomasNordentoft, MereteMors, OleMortensen, Preben BoPsychiatric Genomics Consortium (PGC)Cormand Rifà, BruHougaard, David M.Neale, Benjamin M.Franke, BarbaraFaraone, Stephen V.Børglum, Anders D.Trastorns per dèficit d'atenció amb hiperactivitat en els infantsAgressivitat en els infantsAttention deficit disorder with hyperactivity in childrenAggressiveness in childrenAttention-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.Nature Publishing Group2021202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/173506Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41467-020-20443-2Nature Communications, 2021, vol. 12, num. 1, p. 576https://doi.org/10.1038/s41467-020-20443-2info:eu-repo/grantAgreement/EC/FP7/602805info:eu-repo/grantAgreement/EC/H2020/667302info:eu-repo/grantAgreement/EC/H2020/728018cc-by (c) Demontis, Ditte et al., 2021http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1735062026-05-29T05:05:01Z
dc.title.none.fl_str_mv Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
title Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
spellingShingle Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
Demontis, Ditte
Trastorns per dèficit d'atenció amb hiperactivitat en els infants
Agressivitat en els infants
Attention deficit disorder with hyperactivity in children
Aggressiveness in children
title_short Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
title_full Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
title_fullStr Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
title_full_unstemmed Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
title_sort Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
dc.creator.none.fl_str_mv 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.
author Demontis, Ditte
author_facet 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.
author_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trastorns per dèficit d'atenció amb hiperactivitat en els infants
Agressivitat en els infants
Attention deficit disorder with hyperactivity in children
Aggressiveness in children
topic Trastorns per dèficit d'atenció amb hiperactivitat en els infants
Agressivitat en els infants
Attention deficit disorder with hyperactivity in children
Aggressiveness in children
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/173506
url https://hdl.handle.net/2445/173506
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-020-20443-2
Nature Communications, 2021, vol. 12, num. 1, p. 576
https://doi.org/10.1038/s41467-020-20443-2
info:eu-repo/grantAgreement/EC/FP7/602805
info:eu-repo/grantAgreement/EC/H2020/667302
info:eu-repo/grantAgreement/EC/H2020/728018
dc.rights.none.fl_str_mv cc-by (c) Demontis, Ditte et al., 2021
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Demontis, Ditte et al., 2021
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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