TY - JOUR
T1 - Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD
AU - VA Million Veteran Program
AU - Nielsen, Trine Tollerup
AU - Duan, Jinjie
AU - Levey, Daniel F.
AU - Walters, G. Bragi
AU - Johnson, Emma C.
AU - Thorgeirsson, Thorgeir
AU - Gelernter, Joel
AU - Levey, Daniel F.
AU - Werge, Thomas
AU - Mortensen, Preben Bo
AU - Stefansson, Hreinn
AU - Stefansson, Kari
AU - Hougaard, David M.
AU - Agrawal, Arpana
AU - Gelernter, Joel
AU - Grove, Jakob
AU - Børglum, Anders D.
AU - Demontis, Ditte
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/9
Y1 - 2024/9
N2 - Cannabis use disorder (CUD) and cannabis use (CU) are prevalent conditions co-occurring with attention-deficit hyperactivity disorder (ADHD). Here we report results from a cross-disorder genome-wide association study of ADHD and CUD or CU. We identified 36 concordant genome-wide significant loci for ADHD–CUD and ten loci for ADHD–CU. DRD2 was identified as an ADHD–CUD risk gene. ADHD–CUD risk genes showed high expression across brain tissues and brain developmental stages, which was not observed for ADHD–CU genes. ADHD–CUD and ADHD–CU showed similar genetic correlations with substance use, whereas they differed for substance-use disorders. Individuals with ADHD–CUD had increased polygenic scores (PGS) for psychiatric disorders compared with those with ADHD without CUD and increased burden of rare deleterious variants. Stratification of individuals with ADHD by their CUD PGS revealed an absolute risk of 22% for comorbid CUD in the highest CUD-PGS bin—much higher than 1.6% risk among controls. Sex-specific differences were substantial with an approximately 10% higher CUD risk among men in the highest CUD-PGS bin.
AB - Cannabis use disorder (CUD) and cannabis use (CU) are prevalent conditions co-occurring with attention-deficit hyperactivity disorder (ADHD). Here we report results from a cross-disorder genome-wide association study of ADHD and CUD or CU. We identified 36 concordant genome-wide significant loci for ADHD–CUD and ten loci for ADHD–CU. DRD2 was identified as an ADHD–CUD risk gene. ADHD–CUD risk genes showed high expression across brain tissues and brain developmental stages, which was not observed for ADHD–CU genes. ADHD–CUD and ADHD–CU showed similar genetic correlations with substance use, whereas they differed for substance-use disorders. Individuals with ADHD–CUD had increased polygenic scores (PGS) for psychiatric disorders compared with those with ADHD without CUD and increased burden of rare deleterious variants. Stratification of individuals with ADHD by their CUD PGS revealed an absolute risk of 22% for comorbid CUD in the highest CUD-PGS bin—much higher than 1.6% risk among controls. Sex-specific differences were substantial with an approximately 10% higher CUD risk among men in the highest CUD-PGS bin.
UR - http://www.scopus.com/inward/record.url?scp=85218256097&partnerID=8YFLogxK
U2 - 10.1038/s44220-024-00277-3
DO - 10.1038/s44220-024-00277-3
M3 - Article
AN - SCOPUS:85218256097
SN - 2731-6076
VL - 2
SP - 1071
EP - 1083
JO - Nature Mental Health
JF - Nature Mental Health
IS - 9
M1 - 108535
ER -