Dataset Information

Detection of Significant Association Between Variants in Cannabinoid Receptor 1 Gene (CNR1) and Personality in African-American Population.

ABSTRACT: Background: Several studies have revealed significant associations between single nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 (CNR1) gene and a broad spectrum of psychiatric disorders such as major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), and schizophrenia. Personality traits that are highly related to susceptibility to these conditions have been associated with the CNR1 variants in subjects of Caucasian origin. However, there are no reported studies regarding the effects of CNR1 polymorphisms on personality traits in the African-American (AA) population. Methods: We performed an imputation-based association analysis for 26 CNR1 variants with five dimensions of personality in 3,046 AAs. Results: SNPs rs806372 and rs2180619 showed a significant association with extraversion after Bonferroni correction for multiple testing (p < 0.0019). Further, several extraversion-associated SNPs were significantly associated with conscientiousness, agreeableness, and openness. SNP priority score analysis indicated that SNPs rs806368, rs806371, and rs2180619 play a role in the modulation of personality and psychiatric conditions. Conclusion:CNR1 is important in determining personality traits in the AA population.

SUBMITTER: Yao Y

PROVIDER: S-EPMC6010580 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Detection of Significant Association Between Variants in Cannabinoid Receptor 1 Gene (CNR1) and Personality in African-American Population.

Yao Yinghao Y Xu Yi Y Zhao Junsheng J Ma Yunlong Y Su Kunkai K Yuan Wenji W Ma Jennie Z JZ Payne Thomas J TJ Li Ming D MD

Frontiers in genetics 20180614

Background: Several studies have revealed significant associations between single nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 (CNR1) gene and a broad spectrum of psychiatric disorders such as major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), and schizophrenia. Personality traits that are highly related to susceptibility to these conditions have been associated with the CNR1 variants in subjects of Caucasian origin. However, t ...[more]

PMID: 29963071

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Project description:Importance:The prevalence of nonischemic dilated cardiomyopathy (DCM) is greater in individuals of African ancestry than in individuals of European ancestry. However, little is known about whether the difference in prevalence or outcomes is associated with functional genetic variants. Objective:We hypothesized that Bcl2-associated anthanogene 3 (BAG3) genetic variants were associated with outcomes in individuals of African ancestry with DCM. Design:This multicohort study of the BAG3 genotype in patients of African ancestry with dilated cardiomyopathy uses DNA obtained from African American individuals enrolled in 3 clinical studies: the Genetic Risk Assessment of African Americans With Heart Failure (GRAHF) study; the Intervention in Myocarditis and Acute Cardiomyopathy Trial-2 (IMAC-2) study; and the Genetic Risk Assessment of Cardiac Events (GRACE) study. Samples of DNA were also acquired from the left ventricular myocardium of patients of African ancestry who underwent heart transplant at the University of Colorado and University of Pittsburgh. Main Outcomes and Measures:The primary end points were the prevalence of BAG3 mutations in African American individuals and event-free survival in participants harboring functional BAG3 mutations. Results:Four BAG3 genetic variants were identified; these were expressed in 42 of 402 African American individuals (10.4%) with nonischemic heart failure and 9 of 107 African American individuals (8.4%) with ischemic heart failure but were not present in a reference population of European ancestry (P?<?.001). The variants included 2 nonsynonymous single-nucleotide variants; 1 three-nucleotide in-frame insertion; and 2 single-nucleotide variants that were linked in cis. The presence of BAG3 variants was associated with a nearly 2-fold (hazard ratio, 1.97 [95% CI, 1.19-3.24]; P?=?.01) increase in cardiac events in carriers compared with noncarriers. Transfection of transformed adult human ventricular myocytes with plasmids expressing the 4 variants demonstrated that each variant caused an increase in apoptosis and a decrease in autophagy when samples were subjected to the stress of hypoxia-reoxygenation. Conclusions and Relevance:This study demonstrates that genetic variants in BAG3 found almost exclusively in individuals of African ancestry were not causative of disease but were associated with a negative outcome in patients with a dilated cardiomyopathy through modulation of the function of BAG3. The results emphasize the importance of biological differences in causing phenotypic variance across diverse patient populations, the need to include diverse populations in genetic cohorts, and the importance of determining the pathogenicity of genetic variants.

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

Detection of Significant Association Between Variants in Cannabinoid Receptor 1 Gene (CNR1) and Personality in African-American Population.

Publications

Detection of Significant Association Between Variants in Cannabinoid Receptor 1 Gene (<i>CNR1</i>) and Personality in African-American Population.

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