Back to Search
Start Over
Genome-wide association study implicates CHRNA2 in cannabis use disorder
- Source :
- Nature Neuroscience, Demontis, D, Rajagopal, V M, Thorgeirsson, T E, Als, T D, Grove, J, Leppälä, K, Gudbjartsson, D F, Pallesen, J, Hjorthøj, C, Reginsson, G W, Tyrfingsson, T, Runarsdottir, V, Qvist, P, Christensen, J H, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Huckins, L M, Stahl, E A, Timmermann, A, Agerbo, E, Hougaard, D M, Werge, T, Mors, O, Mortensen, P B, Nordentoft, M, Daly, M J, Stefansson, H, Stefansson, K, Nyegaard, M & Børglum, A D 2019, ' Genome-wide association study implicates CHRNA2 in cannabis use disorder ' Nature Neuroscience . https://doi.org/10.1038/s41593-019-0416-1, Demontis, D, Rajagopal, V M, Thorgeirsson, T E, Als, T D, Grove, J, Leppälä, K, Gudbjartsson, D F, Pallesen, J, Hjorthøj, C, Reginsson, G W, Tyrfingsson, T, Runarsdottir, V, Qvist, P, Christensen, J H, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Huckins, L M, Stahl, E A, Timmermann, A, Agerbo, E, Hougaard, D M, Werge, T, Mors, O, Mortensen, P B, Nordentoft, M, Daly, M J, Stefansson, H, Stefansson, K, Nyegaard, M & Børglum, A D 2019, ' Genome-wide association study implicates CHRNA2 in cannabis use disorder ', Nature Neuroscience, vol. 22, no. 7, pp. 1066-1074 . https://doi.org/10.1038/s41593-019-0416-1, Nat Neurosci, Demontis, D, Rajagopal, V M, Thorgeirsson, T E, Als, T D, Grove, J, Leppälä, K, Gudbjartsson, D F, Pallesen, J, Hjorthøj, C, Reginsson, G W, Tyrfingsson, T, Runarsdottir, V, Qvist, P, Christensen, J H, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Huckins, L M, Stahl, E A, Timmermann, A, Agerbo, E, Hougaard, D M, Werge, T, Mors, O, Mortensen, P B, Nordentoft, M, Daly, M J, Stefansson, H, Stefansson, K, Nyegaard, M & Børglum, A D 2019, ' Genome-wide association study implicates CHRNA2 in cannabis use disorder ', Nature Neuroscience, vol. 22, pp. 1066-1074 . https://doi.org/10.1038/s41593-019-0416-1
- Publication Year :
- 2019
-
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 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. The study reports a genome-wide significant locus for cannabis use disorder, replicating in an independent cohort, and implicates CHRNA2, which encodes an acetylcholine receptor subunit, in the disorder by analyses of genetically regulated gene expression.
- Subjects :
- Male
0301 basic medicine
Marijuana Abuse
Multifactorial Inheritance
Denmark
LOCI
Iceland
Genome-wide association study
Receptors, Nicotinic
ACTIVATION
Cohort Studies
Cognition
0302 clinical medicine
SCHIZOPHRENIA
POLYGENIC RISK
Age of Onset
Genetics
education.field_of_study
HERITABILITY
Research Support, Non-U.S. Gov't
General Neuroscience
PSYCHIATRIC-DISORDERS
Smoking
Brain
Confounding Factors, Epidemiologic
3. Good health
Educational Status
Female
Chromosomes, Human, Pair 8
Quantitative Trait Loci
Population
Nerve Tissue Proteins
Locus (genetics)
Biology
Quantitative trait locus
Polymorphism, Single Nucleotide
Article
MARIJUANA USE
03 medical and health sciences
Research Support, N.I.H., Extramural
NICOTINE
Journal Article
Humans
Genetic Predisposition to Disease
Allele
USE INITIATION
education
METAANALYSIS
Alleles
Gene Expression Profiling
biology.organism_classification
Genetic architecture
030104 developmental biology
Attention Deficit Disorder with Hyperactivity
Case-Control Studies
Expression quantitative trait loci
Schizophrenia
Cannabis
Transcriptome
Neuroscience
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 10976256
- Database :
- OpenAIRE
- Journal :
- Nature Neuroscience
- Accession number :
- edsair.doi.dedup.....b50db1468731ffda6e4321fc6e4f613a
- Full Text :
- https://doi.org/10.1038/s41593-019-0416-1