rs806368
badMag 2.5This is a 3 prime utr variant variant in the CNR1 gene.
Key Literature Trait Associations
Polycystic ovary syndrome
A Polish study of 174 women with PCOS and 125 healthy controls found an approximately 8-fold increased risk associated with the CC genotype of rs806368 (OR=8.81, p=0.0176). The CC genotype was linked to hyperandrogenemia and altered fat distribution patterns in PCOS patients. While the effect size is striking, the study is small and the finding has not been independently replicated; the unusually large OR in a small cohort suggests possible population stratification or chance.
Panic Disorder
The CNR1 gene encodes cannabinoid receptor 1, a key component of the endocannabinoid system that modulates stress recovery and anxiety responses. The C allele of rs806368 in the 3' UTR was associated with increased vulnerability to panic disorder in a case-control study, with the effect more pronounced in females. The endocannabinoid system regulates emotional state through CB1 receptor signaling in the amygdala and prefrontal cortex.
Major depressive disorder
A candidate-gene study of 319 outpatients with major depression and 150 healthy controls found that TT homozygotes at rs806368 had greater risk of non-remission after citalopram treatment compared to C allele carriers (p=0.008), while men carrying the C allele showed better antidepressant response over follow-up (p=0.026). A separate Han Chinese study (n=261) found rs806368 was part of a haplotype block associated with MDD susceptibility and treatment resistance, though the SNP alone did not reach independent significance. Both studies are small, and the direction of effect has not been confirmed in large replication cohorts.
Tardive dyskinesia
In a Chinese cohort of 216 schizophrenia patients, the rs806368 CT genotype was significantly more prevalent in male patients with tardive dyskinesia compared to those without (OR=2.508, 95% CI 1.055–5.961, p=0.037). The CC genotype was associated with higher involuntary limb-trunk movement scores, and borderline effects on visuospatial cognition were noted. The study was limited to antipsychotic-treated schizophrenia patients of Chinese ancestry, and the male-specific finding requires replication in larger, independent populations.
Alcohol dependence
A Spanish candidate-gene study of 298 male alcoholics and 155 healthy controls found that a TGC haplotype at CNR1 (including the C allele of rs806368) was significantly more common in alcohol-dependent individuals (p=0.004), and a gene-environment interaction between rs6454674 G allele and rs806368 C allele was associated with alcohol dependence risk (p=0.009). The effect was observed only in haplotype context; individual allele associations were not independently significant. Findings are from a single small, male-only Spanish cohort and require replication.
Pre-eclampsia
A Central European study of 115 pre-eclamptic women and 145 healthy pregnant controls found significantly different rs806368 genotype distributions between cases and controls (p<0.001), with the CC genotype less common in pre-eclamptic women. In multivariate modeling, rs806368 predicted pre-eclampsia onset (β=0.15, p=0.04), suggesting that the T allele may be associated with increased susceptibility. However, the sample was small (n=260), the study has not been replicated, and the direction of association (T allele at risk) is counter to the C allele's risk direction seen in other CNR1-related conditions.
Obesity
A systematic review of endocannabinoid system polymorphisms across 65 studies found that rs806368 was associated with increased BMI and waist circumference in two independent studies. However, a larger German cohort study (n=2,774) reported only nominal association with obesity in one sub-cohort that was not replicated in a second cohort, and significance was lost after correction for multiple testing. Overall evidence for an independent effect of rs806368 on obesity is weak and inconsistent across populations.
▶Research that mentions this SNP (8)
▶Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disordersAssociationN=1,309Kathryn J. Lester et al.(2017)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
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.
▶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).
▶Risky alcohol consumption in young people is associated with the fatty acid amide hydrolase gene polymorphism C385A and affective rating of drug picturesAssociationN=260Kora-Mareen Bühler et al.(2014)· Molecular Genetics and Genomics
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.
▶Screening genetic variability at the CNR1 gene in both major depression etiology and clinical response to citalopram treatmentAssociationN=469Marina Mitjans et al.(2013)· Psychopharmacology
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).
▶Cannabinoid type 1 receptor gene polymorphisms are not associated with olanzapine-induced weight gainAssociationN=78Young-Min Park et al.(2011)· Human Psychopharmacology: Clinical and Experimental
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.
▶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.
▶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.
▶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.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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