TY - JOUR
T1 - Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
AU - ADHD Working Group of the Psychiatric Genomics Consortium (PGC)
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 - Andreassen, Ole A.
AU - Arranz, Maria Jesús
AU - Banaschewski, Tobias
AU - Bau, Claiton
AU - Bellgrove, Mark
AU - Biederman, Joseph
AU - Brikell, Isabell
AU - Buitelaar, Jan K.
AU - Burton, Christie L.
AU - Casas, Miguel
AU - Crosbie, Jennifer
AU - Doyle, Alysa E.
AU - Ebstein, Richard P.
AU - Elia, Josephine
AU - Elizabeth, Corfield C.
AU - Grevet, Eugenio
AU - Grizenko, Natalie
AU - Havdahl, Alexandra
AU - Hawi, Ziarih
AU - Hebebrand, Johannes
AU - Hervas, Amaia
AU - Hohmann, Sarah
AU - Haavik, Jan
AU - Joober, Ridha
AU - Kent, Lindsey
AU - Kuntsi, Jonna
AU - Langley, Kate
AU - Larsson, Henrik
AU - Lesch, Klaus Peter
AU - Leung, Patrick W.L.
AU - Liao, Calwing
AU - Loo, Sandra K.
AU - Martin, Joanna
AU - Martin, Nicholas G.
AU - Medland, Sarah E.
AU - Miranda, Ana
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
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://www.scopus.com/pages/publications/85099802296
U2 - 10.1038/s41467-020-20443-2
DO - 10.1038/s41467-020-20443-2
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C2 - 33495439
AN - SCOPUS:85099802296
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 576
ER -