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\u2009+\u2009DBDs) 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\u2009+\u2009DBDs across European and Chinese ancestries (rs7118422, P\u2009=\u20093.15×10−10, OR\u2009=\u20091.17). We find a higher SNP heritability for ADHD\u2009+\u2009DBDs (h2SNP\u2009=\u20090.34) when compared to ADHD without DBDs (h2SNP\u2009=\u20090.20), high genetic correlations between ADHD\u2009+\u2009DBDs and aggressive (rg\u2009=\u20090.81) and anti-social behaviors (rg\u2009=\u20090.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD\u2009+\u2009DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD\u2009+\u2009DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.