Genome-wide association study implicates CHRNA2 in cannabis use disorder
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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 α2 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.
Originalsprog | Engelsk |
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Tidsskrift | Nature Neuroscience |
Vol/bind | 22 |
Udgave nummer | 7 |
Sider (fra-til) | 1066-1074 |
ISSN | 1097-6256 |
DOI | |
Status | Udgivet - 2019 |
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596896/pdf/nihms-1622118.pdf
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