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.

• Authors: 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, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Bru Cormand, David M Hougaard, Benjamin M Neale, Barbara Franke, Stephen V Faraone, Anders D Børglum
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 576 (01 25 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 33495439 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Attention Deficit Disorder with Hyperactivity (epidemiology, genetics)
• Attention Deficit and Disruptive Behavior Disorders (epidemiology, genetics)
• Child
• China (epidemiology)
• Cohort Studies
• Comorbidity
• Europe (epidemiology)
• Female
• Genetic Predisposition to Disease (genetics)
• Genome-Wide Association Study (methods)
• Humans
• Male
• Multifactorial Inheritance (genetics)
• Polymorphism, Single Nucleotide
• Risk Factors