rs12720071
badMag 3.5This is a 3 prime utr variant variant in the CNR1 gene.
Key Literature Trait Associations
Panic Disorder
A second CNR1 3' UTR variant ~1 kb downstream of rs806368. The minor C allele of rs12720071 was associated with increased panic disorder vulnerability (p = 0.012) in the same candidate gene study, with a sex-specific pattern showing stronger effects in females. Together with rs806368, these variants implicate endocannabinoid signaling dysfunction in the pathophysiology of panic disorder.
Psychosis
rs12720071 has been implicated in psychosis risk through gene–environment interaction with cannabis use. In the STREAM cohort (143 first-episode psychosis cases, 286 controls; Brazilian), the combination of rs12720071 genotype and lifetime cannabis use was the best-performing multifactor model (p<0.001). Supporting neuroimaging data from smaller US schizophrenia cohorts found that rs12720071 genotype interacted with marijuana use to produce white-matter volume deficits and neurocognitive impairment. These findings are consistent with CB1's role in dopaminergic and glutamatergic signalling relevant to psychosis.
Polycystic ovary syndrome
The GG genotype of rs12720071 has been associated with approximately three-fold higher odds of polycystic ovary syndrome (OR=3.01, p=0.034) and a 3.6-fold increased risk of hyperandrogenemia in women with PCOS, in a Polish case-control study of 174 PCOS patients and 125 controls. A second Polish cohort examining CNR1 variants in PCOS-related non-alcoholic fatty liver disease included rs12720071 in its analysis, though specific effect sizes were not reported for this variant. These findings are preliminary and limited to female populations of Central-European ancestry.
Epilepsy
A 2024 Iranian case-control genetic study found that the rs12720071 genotype was associated with generalized epilepsy with a very large point estimate (OR=16.33, 95% CI 1.8–149, p=0.001). However, the extremely wide confidence interval reflects a small sample size and the finding requires independent replication before clinical weight can be assigned. The biological plausibility is supported by CB1's role in modulating neuronal excitability and seizure thresholds in animal models.
Major depressive disorder
A study of 256 Caucasian patients with major depression found that CNR1 rs12720071, together with rs1049353, was associated with antidepressant treatment resistance, particularly in females with high comorbid anxiety. Functional MRI in a subsample showed that G-allele carriers had reduced amygdala and subcortical activation in response to positive social stimuli, suggesting an emotional processing deficit mediated by CB1 hypofunction. This is a single preliminary study and the variant's role in depression warrants replication.
▶Research that mentions this SNP (4)
▶Longitudinal predictors of cannabis use and dependence in offspring from families at ultra high risk for alcohol dependence and in control familiesAssociationN=338Shirley Y. Hill et al.(2016)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
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).
▶Evidence for association between polymorphisms in the cannabinoid receptor 1 (CNR1) gene and cannabis dependenceAssociationN=1,923Arpana Agrawal et al.(2009)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
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.
▶Cannabinoid Receptor 1 Gene Association With Nicotine DependenceAssociationN=1,649Xiangning Chen et al.(2008)· Archives of General Psychiatry
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 of the cannabinoid receptor gene (CNR1) with ADHD and post‐traumatic stress disorderAssociationN=920Ake T. Lu et al.(2008)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
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.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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