rs6928499

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 4 SNPs (rs6928499, rs806379, rs1535255, rs2023239) in the CNR1 gene exon 3 alternative promoter region in 895 substance-dependent and 472 control subjects, attempting to replicate Zhang et al.'s earlier report of association with polysubstance abuse. A modest association was found for rs1535255 with alcohol dependence in European Americans (P=0.04), but this did not survive multiple testing correction. The study failed to replicate the original findings of association between these CNR1 markers and polysubstance dependence.