rs806380

A longitudinal prospective study of 338 young adult offspring from families at high and low risk for alcohol dependence examined predictors of cannabis use patterns and cannabis abuse/dependence from ages 8-30. A low P300 amplitude trajectory in childhood predicted cannabis abuse/dependence in males (P=0.01). A four-SNP ANKK1-DRD2 haplotype (rs4938012-rs4938015-rs1800497-rs6277, G-G-G-C) was significantly associated with cannabis use frequency patterns (P=0.0008). Among individuals with cannabis abuse/dependence, the CNR1 rs806368 A>G minor allele conferred a 5.4-fold increase in likelihood of frequent persistent use versus declining use (P=0.003, OR=5.4).

This association study examined polymorphisms in the cannabinoid receptor 1 (CNR1) gene and cannabis dependence in 1,923 individuals from the COGA family study. Two SNPs showed significant association with DSM-III-R cannabis dependence: rs806380 (p=0.009) and rs806368 (p=0.05), with rs806380 driving the haplotype association. Results support a role for CNR1 variation in cannabis dependence risk.

This candidate gene association study tested the hypothesis that the cannabinoid receptor 1 (CNR1) gene is associated with nicotine dependence across two independent samples from the Mid-Atlantic Twin Registry. In the VAND sample (n=688), haplotype 1-1-2 of markers rs2023239-rs12720071-rs806368 showed female-specific association with nicotine dependence and smoking initiation (P<.001 for SI, P=.02 for ND). Replication in the VAANX sample (n=961) confirmed female-specific haplotype associations with FTND score (P=.009 for haplotype 1-1-2 of combination 7-9-10). The findings suggest sex-specific genetic effects of CNR1 variants on nicotine dependence risk.

This association study examined four SNPs in the CNR1 gene (encoding the cannabinoid receptor) in 541 adolescents (327 cases with cannabis dependence symptoms, 214 controls without symptoms). SNP rs806380 (A/G, located in intron 2) showed significant association with protection from cannabis dependence symptoms (p=0.034, protective effect for G allele). A common haplotype (GGCC, present in 21% of subjects) was significantly associated with fewer cannabis dependence symptoms in the overall sample (LRT=16.47, p=0.021), though effects were attenuated in stratified ethnic analyses.