Genome-wide association study implicates CHRNA2 in cannabis use disorder.

ABSTRACT: Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 cases and 48,985 controls, followed by replication in 5,501 cases and 301,041 controls. We report a genome-wide significant risk locus for CUD (P?=?9.31?×?10-12) that replicates in an independent population (Preplication?=?3.27?×?10-3, Pmeta-analysis?=?9.09?×?10-12). The index variant (rs56372821) is a strong expression quantitative trait locus for cholinergic receptor nicotinic ?2 subunit (CHRNA2); analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with CUD in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance. The results provide biological insights and inform on the genetic architecture of CUD.

SUBMITTER: Demontis D 

PROVIDER: S-EPMC7596896 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature