rs1049353

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.

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 candidate gene association study examined 10 SNPs in addiction-related genes (CNR1, FAAH, DRD2, ANKK1, COMT, OPRM1) in university students and identified the FAAH C385A (rs324420) CC genotype as significantly associated with risky alcohol consumption (p=0.006, OR=2.38). The finding was replicated in an independent sample of 83 participants. Additionally, affective ratings of drug-related pictures were positively correlated with alcohol, tobacco, and cannabis consumption.

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 genetic association study examined whether rs1049353 (CNR1 endocannabinoid receptor gene) moderates the effect of childhood physical abuse on anhedonia and depression. In the primary sample of 1,041 young adult women, carriers of the minor A allele showed attenuation of the abuse-anhedonia relationship (57% of GG individuals with abuse reported anhedonia vs. only 29% of AA/AG carriers; interaction OR=0.31, p=0.014). These findings were replicated in an independent sample of 1,934 Australian heroin-dependent individuals and controls (interaction OR=0.79, p=0.02). The protective effect of the rs1049353 A allele on major depressive disorder was largely attributable to its effect on anhedonic depression.

Genetic association study of cancer cachexia identified 129 SNPs in 80 candidate genes in 775 cancer patients. The C allele of rs6136 in the SELP gene (encoding P-selectin) was significantly associated with reduced risk of cancer cachexia (weight loss >10%) in both the main study (OR 0.52; p=0.026) and validation cohort (OR 0.09; p=0.035). Multiple other genes including APEH, GHRL, TNFRSF1A, and CNR1 showed significant associations with cachexia-related traits.

A candidate gene association study of 78 Korean schizophrenia patients found no significant association between three CNR1 polymorphisms (rs1049353, rs806368, rs4707436) and olanzapine-induced weight gain (all p>0.05). Genotype, allele, and haplotype frequencies did not differ between patients with ≥7% and <7% weight gain.

This longitudinal study of 154 traumatized injury survivors examined associations between circulating endocannabinoids and CNR1/FAAH/MGLL genetic variants with depression severity at 6 months post-injury. Higher post-injury serum 2-arachidonylglycerol (2-AG) concentrations predicted greater depression severity at 6 months (β = 0.23, p = 0.007), and carriers of the minor allele (G) at CNR1 rs806371 experienced significantly greater depression (β = 0.19, p = 0.024), supporting a role for endocannabinoid system dysfunction in post-trauma depression risk.

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.

Association study of the cannabinoid receptor gene (CNR1) in two independent samples found a haplotype (C-G2) significantly associated with ADHD in Finnish adolescents (P = 0.008), with a threefold increased risk in males. A single SNP (rs1049353, allele A, P = 0.011) and alternative haplotype (C-A1, P = 0.04) were associated with post-traumatic stress disorder in LA Caucasian parents, suggesting CNR1 may be a risk factor for ADHD and possibly PTSD.

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.