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