1. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder.
- Author
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Demontis D, Walters RK, Rajagopal VM, Waldman ID, Grove J, Als TD, Dalsgaard S, Ribasés M, Bybjerg-Grauholm J, Bækvad-Hansen M, Werge T, Nordentoft M, Mors O, Mortensen PB, Cormand B, Hougaard DM, Neale BM, Franke B, Faraone SV, and Børglum AD
- Subjects
- Attention Deficit Disorder with Hyperactivity epidemiology, Attention Deficit and Disruptive Behavior Disorders epidemiology, Child, China epidemiology, Cohort Studies, Comorbidity, Europe epidemiology, Female, Humans, Male, Risk Factors, Attention Deficit Disorder with Hyperactivity genetics, Attention Deficit and Disruptive Behavior Disorders genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study methods, Multifactorial Inheritance genetics, Polymorphism, Single Nucleotide
- 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 (h2 SNP = 0.34) when compared to ADHD without DBDs (h2 SNP = 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.- Published
- 2021
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