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

2021 | journal article. A publication with affiliation to the University of Göttingen.

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​Demontis, D., Walters, R. K., Rajagopal, V. M., Waldman, I. D., Grove, J., Als, T. D., Dalsgaard, S. ... Børglum, A. D. (2021). ​Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder. Nature Communications12(1), . ​doi: https://doi.org/10.1038/s41467-020-20443-2 

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Authors Group
ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
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Authors
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; Børglum, Anders D.
Abstract
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 (h 2 SNP  = 0.34) when compared to ADHD without DBDs (h 2 SNP  = 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.
Issue Date
2021
Journal
Nature Communications 
eISSN
2041-1723
Language
English

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