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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 Bybjerg-Grauholm, Jonas Bækvad-Hansen, Maria
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
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Nature Communications
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2021-01-25
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12
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1
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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.