TY - UNPB
T1 - Genome-wide association study implicates CHRNA2 in cannabis use disorder
AU - Demontis, Ditte
AU - Rajagopal, Veera Manikandan
AU - Als, Thomas D.
AU - Grove, Jakob
AU - Pallesen, Jonatan
AU - Hjorthøj, Carsten
AU - Qvist, Per
AU - Christensen, Jane Hvarregaard
AU - Bybjerg-Grauholm, Jonas
AU - Bækvad-Hansen, Marie
AU - Huckins, Laura M.
AU - Stahl, Eli A.
AU - Timmermann, Allan
AU - Agerbo, Esben
AU - Hougaard, David M.
AU - Werge, Thomas
AU - Mors, Ole
AU - Mortensen, Preben Bo
AU - Nordentoft, Merete
AU - Daly, Mark
AU - Nyegaard, Mette
AU - Børglum, Anders D.
PY - 2017/12/21
Y1 - 2017/12/21
N2 - Cannabis is the most frequently used illicit psychoactive substance worldwide1. Life time use has been reported among 35-40% of adults in Denmark2 and the United States3. Cannabis use is increasing in the population4–6 and among users around 9% become dependent7. The genetic risk component is high with heritability estimates of 518–70%9. Here we report the first genome-wide significant risk locus for cannabis use disorder (CUD, P=9.31×10−12) that replicates in an independent population (Preplication=3.27×10−3, Pmetaanalysis=9.09×10−12). The finding is based on a genome-wide association study (GWAS) of 2,387 cases and 48,985 controls followed by replication in 5,501 cases and 301,041 controls. The index SNP (rs56372821) is a strong eQTL for CHRNA2 and analyses of the genetic regulated gene expressions identified significant association of CHRNA2 expression in cerebellum with CUD. This indicates a potential therapeutic use in CUD of compounds with agonistic effect on the neuronal acetylcholine receptor alpha-2 subunit encoded by CHRNA2. At the polygenic level analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance.
AB - Cannabis is the most frequently used illicit psychoactive substance worldwide1. Life time use has been reported among 35-40% of adults in Denmark2 and the United States3. Cannabis use is increasing in the population4–6 and among users around 9% become dependent7. The genetic risk component is high with heritability estimates of 518–70%9. Here we report the first genome-wide significant risk locus for cannabis use disorder (CUD, P=9.31×10−12) that replicates in an independent population (Preplication=3.27×10−3, Pmetaanalysis=9.09×10−12). The finding is based on a genome-wide association study (GWAS) of 2,387 cases and 48,985 controls followed by replication in 5,501 cases and 301,041 controls. The index SNP (rs56372821) is a strong eQTL for CHRNA2 and analyses of the genetic regulated gene expressions identified significant association of CHRNA2 expression in cerebellum with CUD. This indicates a potential therapeutic use in CUD of compounds with agonistic effect on the neuronal acetylcholine receptor alpha-2 subunit encoded by CHRNA2. At the polygenic level analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance.
U2 - 10.1101/237321
DO - 10.1101/237321
M3 - Preprint
BT - Genome-wide association study implicates CHRNA2 in cannabis use disorder
PB - bioRxiv
ER -