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

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, Cormand, Bru, Hougaard, David M., Neale, Benjamin M., Franke, Barbara, Faraone, Stephen V., Børglum, Anders D., ADHD Working Group of the Psychiatric Genomics Consortium (PGC), , Anney, Richard J. L., Thapar, Anita and Martin, Joanna 2021. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder. Nature Communications 12 (1) , 576. 10.1038/s41467-020-20443-2

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology
Additional Information:	Richard J. L. Anney, Anita Thapar and Joanna Martin are members of the ADHD Working Group of the Psychiatric Genomics Consortium (PGC
ISSN:	20411723
Date of First Compliant Deposit:	11 February 2021
Date of Acceptance:	30 November 2020
Last Modified:	18 Feb 2021 15:30
URI:	http://orca.cf.ac.uk/id/eprint/138474

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