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

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=3.15x10(-10), OR=1.17). We find a higher SNP heritability for ADHD+DBDs (h(SNP)(2)=0.34) when compared to ADHD without DBDs (h(SNP)(2)=0.20), high genetic correlations between ADHD+DBDs and aggressive (r(g)=0.81) and anti-social behaviors (r(g)=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. ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.