Genome-wide association study implicates CHRNA2 in cannabis use disorder
| Autor: | Mette Nyegaard, Per Qvist, Jakob Grove, Laura M. Huckins, Preben Bo Mortensen, Thomas Damm Als, Ditte Demontis, Ole Mors, Eli A. Stahl, Valgerdur Runarsdottir, Carsten Hjorthøj, Veera M. Rajagopal, Thorgeir E. Thorgeirsson, Allan Timmermann, Esben Agerbo, Mark J. Daly, Jonatan Pallesen, Anders D. Børglum, Merete Nordentoft, Kari Stefansson, Gunnar W Reginsson, Thomas Werge, Jane H. Christensen, Hreinn Stefánsson, Thorarinn Tyrfingsson |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0303 health sciences
education.field_of_study Population Genome-wide association study Locus (genetics) Heritability Biology biology.organism_classification 3. Good health 03 medical and health sciences 0302 clinical medicine Expression quantitative trait loci SNP Cannabis Effects of sleep deprivation on cognitive performance education 030217 neurology & neurosurgery 030304 developmental biology Demography |
| DOI: | 10.1101/237321 |
| Popis: | Introductory paragraphCannabis 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. |
| Databáze: | OpenAIRE |
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