Title: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder.
Authors: Demontis, Ditte; Walters, Raymond K; Rajagopal, Veera M; Waldman, Irwin D; Grove, Jakob; Als, Thomas D; Dalsgaard, Søren; Ribasés, Marta; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Maria; Werge, Thomas; Nordentoft, Merete; Mors, Ole; Mortensen, Preben Bo; ADHD Working Group of the Psychiatric Genomics Consortium (PGC); Cormand, Bru; Hougaard, David M; Neale, Benjamin M; Franke, Barbara; Faraone, Stephen V; Børglum, Anders D
Published In Nat Commun, (2021 01 25)
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.
PubMed ID: 33495439
MeSH Terms: Attention Deficit Disorder with Hyperactivity/epidemiology; Attention Deficit Disorder with Hyperactivity/genetics*; Attention Deficit and Disruptive Behavior Disorders/epidemiology; Attention Deficit and Disruptive Behavior Disorders/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