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

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Demontis_2021_NatComm_Risk_variants_CC.pdf (1.018Mb)
Date
25/01/2021
Author
Demontis, Ditte
Walters, Raymond K.
Rajagopal, Veera M.
Waldman, Irwin D.
Grove, Jakob
Als, Thomas D.
Dalsgaard, Søren
Ribasas, Marta
Bybjerg-Grauholm, Jonas
Bækvad-Hansen, Maria
Werge, Thomas
Nordentoft, Merete
Mors, Ole
Mortensen, Preben Bo
(PGC), ADHD Working Group of the Psychiatric Genomics Consortium
Andreassen, Ole A.
Arranz, Maria Jesús
Banaschewski, Tobias
Bau, Claiton
Bellgrove, Mark
Biederman, Joseph
Brikell, Isabell
Buitelaar, Jan K.
Burton, Christie L.
Casas, Miguel
Crosbie, Jennifer
Doyle, Alysa E.
Ebstein, Richard P.
Elia, Josephine
Elizabeth, Corfield C.
Grevet, Eugenio
Grizenko, Natalie
Havdahl, Alexandra
Hawi, Ziarih
Hebebrand, Johannes
Hervas, Amaia
Hohmann, Sarah
Haavik, Jan
Joober, Ridha
Kent, Lindsey
Kuntsi, Jonna
Langley, Kate
Larsson, Henrik
Lesch, Klaus-Peter
Leung, Patrick W. L.
Liao, Calwing
Loo, Sandra K.
Martin, Joanna
Martin, Nicholas G.
Medland, Sarah E.
Miranda, Ana
Mota, Nina Roth
Oades, Robert D.
Ramos-Quiroga, Josep Antoni
Reif, Andreas
Rietschel, Marcella
Roeyers, Herbert
Rohde, Luis Augusto
Rothenberger, Aribert
Rovira, Paula
Sánchez-Mora, Cristina
Schachar, Russell James
Sengupta, Sarojini
Artigas, Maria Soler
Steinhausen, Hans-Christoph
Thapar, Anita
Witt, Stephanie H.
Yang, Li
Zayats, Tetyana
Zhang-James, Yanli
Cormand, Bru
Hougaard, David M.
Neale, Benjamin M.
Franke, Barbara
Faraone, Stephen V.
Børglum, Anders D.
Keywords
ADHD
Genome-wide association studies
QH426 Genetics
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
DAS
Metadata
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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.
Citation
Demontis , D , Walters , R K , Rajagopal , V M , Waldman , I D , Grove , J , Als , T D , Dalsgaard , S , Ribasas , M , Bybjerg-Grauholm , J , Bækvad-Hansen , M , Werge , T , Nordentoft , M , Mors , O , Mortensen , P B , (PGC) , ADHD W G O T P G C , Andreassen , O A , Arranz , M J , Banaschewski , T , Bau , C , Bellgrove , M , Biederman , J , Brikell , I , Buitelaar , J K , Burton , C L , Casas , M , Crosbie , J , Doyle , A E , Ebstein , R P , Elia , J , Elizabeth , C C , Grevet , E , Grizenko , N , Havdahl , A , Hawi , Z , Hebebrand , J , Hervas , A , Hohmann , S , Haavik , J , Joober , R , Kent , L , Kuntsi , J , Langley , K , Larsson , H , Lesch , K-P , Leung , P W L , Liao , C , Loo , S K , Martin , J , Martin , N G , Medland , S E , Miranda , A , Mota , N R , Oades , R D , Ramos-Quiroga , J A , Reif , A , Rietschel , M , Roeyers , H , Rohde , L A , Rothenberger , A , Rovira , P , Sánchez-Mora , C , Schachar , R J , Sengupta , S , Artigas , M S , Steinhausen , H-C , Thapar , A , Witt , S H , Yang , L , Zayats , T , Zhang-James , Y , Cormand , B , Hougaard , D M , Neale , B M , Franke , B , Faraone , S V & Børglum , A D 2021 , ' Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder ' , Nature Communications , vol. 12 , no. 1 , 576 . https://doi.org/10.1038/s41467-020-20443-2
Publication
Nature Communications
Status
Peer reviewed
DOI
https://doi.org/10.1038/s41467-020-20443-2
ISSN
2041-1723
Type
Journal article
Rights
Copyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Collections
  • University of St Andrews Research
URL
https://www.nature.com/articles/s41467-021-21566-w
URI
http://hdl.handle.net/10023/21375

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