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

Ditte Demontis (), Raymond K. Walters, Veera M. Rajagopal, Irwin D. Waldman, Jakob Grove, Thomas D. Als, Søren Dalsgaard, Marta Ribasés, Jonas Bybjerg-Grauholm, Maria Bækvad-Hansen, Thomas Werge, Merete Nordentoft, Ole Mors, Preben Bo Mortensen, Bru Cormand, David M. Hougaard, Benjamin M. Neale, Barbara Franke, Stephen V. Faraone () and Anders D. Børglum ()
Additional contact information
Ditte Demontis: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Raymond K. Walters: Massachusetts General Hospital and Harvard Medical School
Veera M. Rajagopal: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Irwin D. Waldman: Emory University
Jakob Grove: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Thomas D. Als: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Søren Dalsgaard: Aarhus University
Marta Ribasés: Universitat Autònoma de Barcelona
Jonas Bybjerg-Grauholm: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Maria Bækvad-Hansen: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Thomas Werge: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Merete Nordentoft: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Ole Mors: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Preben Bo Mortensen: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Bru Cormand: Universitat de Barcelona
David M. Hougaard: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Benjamin M. Neale: Massachusetts General Hospital and Harvard Medical School
Barbara Franke: Radboud University Medical Center
Stephen V. Faraone: SUNY Upstate Medical University
Anders D. Børglum: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20443-2

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