Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
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
ISSN
2041-1723Type
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/.
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