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Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder.

ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder affecting some 5-10% of children and 4-5% of adults. The cannabinoid receptor gene (CNR1) is a positional candidate gene due to its location near an identified ADHD linkage peak on chromosome 6, its role in stress and dopamine regulation, its association with other psychiatric disorders that co-occur with ADHD, and its function in learning and memory. We tested SNP variants at the CNR1 gene in two independent samples-an unselected adolescent sample from Northern Finland, and a family-based sample of trios (an ADHD child and their parents). In addition to using the trios for association study, the parents (with and without ADHD) were used as an additional case/control sample of adults for association tests. ADHD and its co-morbid psychiatric disorders were examined. A significant association was detected for a SNP haplotype (C-G) with ADHD (P = 0.008). A sex by genotype interaction was observed as well with this haplotype posing a greater risk in males than females. An association of an alternative SNP haplotype in this gene was found for post-traumatic stress disorder (PTSD) (P = 0.04 for C-A, and P = 0.01 for C-G). These observations require replication, however, they suggest that the CNR1 gene may be a risk factor for ADHD and possibly PTSD, and that this gene warrants further investigation for a role in neuropsychiatric disorders.

SUBMITTER: Lu AT

PROVIDER: S-EPMC2685476 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder.

Lu Ake T AT Ogdie Matthew N MN Järvelin Marjo-Ritta MR Moilanen Irma K IK Loo Sandra K SK McCracken James T JT McGough James J JJ Yang May H MH Peltonen Leena L Nelson Stanley F SF Cantor Rita M RM Smalley Susan L SL

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20081201 8

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder affecting some 5-10% of children and 4-5% of adults. The cannabinoid receptor gene (CNR1) is a positional candidate gene due to its location near an identified ADHD linkage peak on chromosome 6, its role in stress and dopamine regulation, its association with other psychiatric disorders that co-occur with ADHD, and its function in learning and memory. We tested SNP variants at the CNR1 gene in two independent samples- ...[more]

PMID: 18213623

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Project description:Background:Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder of unknown etiology, although a major role of genetic factors has been established. Cannabis-based medicines may alleviate GTS-associated tics and variants of CNR1 gene encoding central cannabinoid receptor (CB1) are believed to be a risk factor for the development of some neurodevelopmental diseases. Our aim was to test the association of selected CNR1 gene variants with GTS. Material and Methods:The cohort of GTS cases comprised 262 unrelated patients aged 3-53 years (mean age: 18.3 ± 9.1 years; 204 males (77.9%), 126 (48.1%) adults defined as ?18 years). As a control group we enrolled 279 unrelated, ethnically and gender matched individuals with no diagnosed mental, neurological or general disorder, aged 13-54 years (mean age: 22.5 ± 3.0 years; 200 males, (74.1%). Both study and control groups were selected from Polish population, which is ethnically homogenous subgroup of Caucasian population. Four single nucleotide polymorphisms (SNPs) in CNR1 were selected: rs2023239, rs2180619, rs806379, and rs1049353 based on minor allele frequency in general population >15%. These variants were genotyped using a real-time quantitative polymerase chain reaction system (TaqMan SNP genotyping assay). Results:We found significant association of GTS clinical phenotype with rs2023239 variant. Minor allele C and CT+CC genotypes were found significantly more often in GTS patients compared to controls (17.4 vs 11.1%, p=0.003 and 32.8 vs 20.4%, p=0.001, respectively), and the difference remained significant after correction for multiple testing. C allele of rs2023239 polymorphism of the CNR1 gene was associated with the occurrence of tics. There were no statistically significant associations for rs806379, rs1049353 or rs2180619 variants. Conclusion:Our findings suggest that C allele of rs2023239 polymorphism of the CNR1 gene is a risk factor of GTS in Polish population. The variant can be potentially associated with abnormal endocannabinoid transmission, which is suspected to be one of the causes of GTS.

Dataset Information

Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder.

Publications

Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder.

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