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. ORCID: https://orcid.org/0000-0002-6083-407X, Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X and Martin, Joanna ORCID: https://orcid.org/0000-0002-8911-3479 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:	08 May 2023 21:24
URI:	https://orca.cardiff.ac.uk/id/eprint/138474

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