TY - JOUR
T1 - Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
AU - Demontis, Ditte
AU - Walters, Raymond K
AU - Rajagopal, Veera M
AU - Waldman, Irwin D
AU - Grove, Jakob
AU - Als, Thomas D
AU - Dalsgaard, Søren
AU - Ribasas, Marta
AU - Bybjerg-Grauholm, Jonas
AU - Bækvad-Hansen, Maria
AU - Werge, Thomas
AU - Nordentoft, Merete
AU - Mors, Ole
AU - Mortensen, Preben Bo
AU - ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
AU - Cormand, Bru
AU - Hougaard, David M
AU - Neale, Benjamin M
AU - Franke, Barbara
AU - Faraone, Stephen V
AU - Børglum, Anders D
A2 - Steinhausen, Hans Christoph
PY - 2021/1/25
Y1 - 2021/1/25
N2 - 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.
AB - 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.
UR - https://doi.org/10.1038/s41467-021-21566-w
U2 - 10.1038/s41467-020-20443-2
DO - 10.1038/s41467-020-20443-2
M3 - Journal article
C2 - 33495439
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
M1 - 576
ER -