rs1535255

This study investigated genetic variation in the endocannabinoid system (CNR1, CNR2, FAAH genes) as a predictor of response to cognitive behavior therapy for childhood anxiety disorders in 1,309 children aged 5-17 years. Six SNPs showed nominal associations (P<0.05) with treatment response during follow-up: rs806365 (CNR1, P=0.004), rs2501431 (CNR2), rs2070956 (CNR2), rs7769940 (CNR1), rs2209172 (FAAH) associated with poorer response, and rs6928813 (CNR1) with better response. Only rs806365 survived multiple testing corrections in the fear-based anxiety disorder subset (P=0.0011). The authors conclude there is very limited evidence for genetic variation in endocannabinoid system genes predicting CBT treatment response.

This case-control association study analyzed five CNR1 gene polymorphisms (rs806368, rs1049353, rs806371, rs806377, rs1535255) in 319 major depression patients and 150 healthy controls, plus a pharmacogenetic subsample of 155 depressed patients treated with citalopram. The rs806371 G carrier genotype showed higher frequency in MD with melancholia (p=0.018) and psychotic symptoms (p=0.007). For treatment response, rs806368 and rs806371 TT homozygotes had increased risk of no remission at 12 weeks (OR=2.64 and OR=2.8, respectively). A significant time-sex-genotype interaction was found for rs806368, with C carrier men showing better antidepressant response throughout follow-up (p=0.026).

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 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.