Evidence for association between polymorphisms in the cannabinoid receptor 1 (CNR1) gene and cannabis dependence

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 150B; no. 5; pp. 736 - 740
• Main Authors: Agrawal, Arpana, Wetherill, Leah, Dick, Danielle M., Xuei, Xiaoling, Hinrichs, Anthony, Hesselbrock, Victor, Kramer, John, Nurnberger Jr, John I., Schuckit, Marc, Bierut, Laura J., Edenberg, Howard J., Foroud, Tatiana
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05-07-2009; Wiley-Liss
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; association; Biological and medical sciences; cannabis dependence; CNR1; COGA; Female; Gene Frequency; Genotype; Humans; Linkage Disequilibrium; Male; Marijuana Abuse - genetics; Medical genetics; Medical sciences; Middle Aged; pedigree disequilibrium test; Polymorphism, Single Nucleotide; Receptor, Cannabinoid, CB1 - genetics; Young Adult; cannabis dependence; Association; Gene; Family study; Pedigree; CNR1; pedigree disequilibrium test; Dependence; COGA; Polymorphism; Biological receptor
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30881

Genomic studies of cannabis use disorders have been limited. The cannabinoid receptor 1 gene (CNR1) on chromosome 6q14‐15 is an excellent candidate gene for cannabis dependence due to the important role of the G‐protein coupled receptor encoded by this gene in the rewarding effects of Δ9‐tetrahydrocannabinol. Previous studies have found equivocal evidence for an association between SNPs in CNR1 and a general vulnerability to substance use disorders. We investigate the association between 9 SNPs spanning CNR1 and cannabis dependence in 1,923 individuals. Two SNPs that were previously associated with cannabis dependence in other studies were also significant with this phenotype in our analyses [rs806368 (P = 0.05) and rs806380 (P = 0.009)]. Haplotype analyses revealed the association to be largely driven by the SNP rs806380. These results suggest a role for the cannabinoid receptor 1 gene in cannabis dependence. © 2008 Wiley‐Liss, Inc.