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

Demontis, Ditte; Walters, Raymond K; Rajagopal, Veera M; Waldman, Irwin D; Grove, Jakob; Als, Thomas D; Dalsgaard, Søren; Ribasés, Marta et al. · Nat Commun · 2021

meta_analysis · Level I

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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<sup>-10</sup>, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h<sup>2</sup><sub>SNP</sub> = 0.34) when compared to ADHD without DBDs (h<sup>2</sup><sub>SNP</sub> = 0.20), high genetic correlations between ADHD + DBDs and aggressive (r<sub>g</sub> = 0.81) and anti-social behaviors (r<sub>g</sub> = 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.

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