Dataset Information

Dimensional Traits of Schizotypy Associated With Glycine Receptor GLRA1 Polymorphism: An Exploratory Candidate-Gene Association Study.

ABSTRACT: Schizotypy captures the underlying genetic vulnerability to schizophrenia. However, the genetic underpinnings of schizotypy remain unexplored. The authors examined the relationship between single nucleotide poly-morphisms (SNPs) and schizotypy. A sample of 137 subjects (43 healthy controls, 34 subjects with schizotypal personality disorder [SPD], 32 with borderline personality disorder, and 25 with other personality disorders) completed the Schizotypal Personality Questionnaire (SPQ). Subjects were genotyped using a custom array chip. Principal component analysis was used to cluster SPQ variables. Linear regression tested for associations between dimensional schizotypy and SNPs. Logistic regression tested for associations between SNPs and SPD diagnosis. There were significant associations between the minor alleles of three SNPs within the glycine receptor alpha 1 subunit (GLRA1) and the disorganized schizotypy dimension, even after Bonferroni correction. There were no significant associations between any SNPs and the categorical SPD diagnosis. Glycine receptor pathways may have an impact on dimensional traits of psychosis.

SUBMITTER: Vora AK

PROVIDER: S-EPMC5856645 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Dimensional Traits of Schizotypy Associated With Glycine Receptor GLRA1 Polymorphism: An Exploratory Candidate-Gene Association Study.

Vora Anvi K AK Fisher Amanda M AM New Antonia S AS Hazlett Erin A EA McNamara Margaret M Yuan Qiaoping Q Zhou Zhifeng Z Hodgkinson Colin C Goldman David D Siever Larry J LJ Roussos Panos P Perez-Rodriguez M Mercedes MM

Journal of personality disorders 20170731 3

Schizotypy captures the underlying genetic vulnerability to schizophrenia. However, the genetic underpinnings of schizotypy remain unexplored. The authors examined the relationship between single nucleotide poly-morphisms (SNPs) and schizotypy. A sample of 137 subjects (43 healthy controls, 34 subjects with schizotypal personality disorder [SPD], 32 with borderline personality disorder, and 25 with other personality disorders) completed the Schizotypal Personality Questionnaire (SPQ). Subjects w ...[more]

PMID: 28758885

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Project description:Glycine receptors (GlyRs) are ligand-gated chloride channels mediating inhibitory neurotransmission in the brain stem and spinal cord. They function as pentamers composed of alpha and beta subunits for which 5 genes have been identified in human (GLRA1, GLRA2, GLRA3, GLRA4, GLRB). Several in vitro studies showed that the pentameric subtype composition as well as its stoichiometry influence the distribution and the molecular function of the receptor. Moreover, mutations in some of these genes are involved in different human conditions ranging from tinnitus to epilepsy and hyperekplexia, suggesting distinct functions of the different subunits. Although the beta subunit is essential for synaptic clustering of the receptor, the specific role of each alpha subtype is still puzzling in vivo. The zebrafish genome encodes for five glycine receptor alpha subunits (glra1, glra2, glra3, glra4a, glra4b) thus offering a model of choice to investigate the respective role of each subtype on general motor behaviour. After establishing a phylogeny of GlyR subunit evolution between human and zebrafish, we checked the temporal expression pattern of these transcripts during embryo development. Interestingly, we found that glra1 is the only maternally transmitted alpha subunit. We also showed that the expression of the different GlyR subunits starts at different time points during development. Lastly, in order to decipher the role of each alpha subunit on the general motor behaviour of the fish, we knocked out individually each alpha subunit by CRISPR/Cas9-targeted mutagenesis. Surprisingly, we found that knocking out any of the alpha2, 3, a4a or a4b subunit did not lead to any obvious developmental or motor phenotype. However, glra1-/- (hitch) embryos depicted a strong motor dysfunction from 3 days, making them incapable to swim and thus leading to their premature death. Our results infer a strong functional redundancy between alpha subunits and confirm the central role played by glra1 for proper inhibitory neurotransmission controlling locomotion. The genetic tools we developed here will be of general interest for further studies aiming at dissecting the role of GlyRs in glycinergic transmission in vivo and the hitch mutant (hic) is of specific relevance as a new model of hyperekplexia.

Project description:Compared to other addictive substances, patients with cannabis addiction are significantly outnumbered by those who report dependence on other, more addictive substances. Unfortunately, most cannabis addiction goes untreated, and among those who choose treatment, the requirements are much higher for adolescents and young adults.The aim of the studyTo examine the relationship of cannabinoid dependency in the genetic context-the association between the rs1799732 polymorphism of the DRD2 gene and psychological traits and anxiety.MethodsThe study group consisted of 515 male volunteers. Of these, 214 patients were diagnosed with cannabis addiction and 301 were non-addicted. Patients were diagnosed with NEO Five-Factor Personality Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI) questionnaires. The interactions between personality traits and polymorphisms in the DRD2 rs1799732 gene were investigated in a group of cannabis-addicted patients and non-addicted controls using the real-time PCR method.ResultsCompared to the control group, the case group obtained significantly higher scores on the STAI State, STAI Trait, Neuroticism and Openness scales, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness scales. There was no statistically significant difference between addicts and the control group in the frequency of genotypes, but there was a statistically significant difference between addicts and the control group in the frequency of the DRD2 allele rs179973. The multivariate ANOVA analysis showed a statistically significant influence of the DRD2 rs1799732 genotype on the NEO-FFI agreeableness scale and a statistically significant effect of addiction to cannabinoids or its absence on the NEO-FFI agreeableness scale score.ConclusionsStudying homogeneous subgroups-as in our study-seems reasonable, particularly when combined with genetic determinants and psychological traits. In multigenic and multifactorial entities, such a strategy has a future.

Project description:Soybean (Glycine max [L.] Merr.) is one of the most significant crops in the world in terms of oil and protein. Owing to the rising demand for soybean products, there is an increasing need for improved varieties for more productive farming. However, complex correlation patterns among quantitative traits along with genetic interactions pose a challenge for soybean breeding. Association studies play an important role in the identification of accession with useful alleles by locating genomic sites associated with the phenotype in germplasm collections. In the present study, a genome-wide association study was carried out for seven agronomic and yield-related traits. A field experiment was conducted in 2015/2016 at two locations that include 155 diverse soybean germplasm. These germplasms were genotyped using SoySNP50K Illumina Infinium Bead-Chip. A total of 51 markers were identified for node number, plant height, pods per plant, seeds per plant, seed weight per plant, hundred-grain weight, and total yield using a multi-locus linear mixed model (MLMM) in FarmCPU. Among these significant SNPs, 18 were putative novel QTNs, while 33 co-localized with previously reported QTLs. A total of 2,356 genes were found in 250 kb upstream and downstream of significant SNPs, of which 17 genes were functional and the rest were hypothetical proteins. These 17 candidate genes were located in the region of 14 QTNs, of which ss715580365, ss715608427, ss715632502, and ss715620131 are novel QTNs for PH, PPP, SDPP, and TY respectively. Four candidate genes, Glyma.01g199200, Glyma.10g065700, Glyma.18g297900, and Glyma.14g009900, were identified in the vicinity of these novel QTNs, which encode lsd one like 1, Ergosterol biosynthesis ERG4/ERG24 family, HEAT repeat-containing protein, and RbcX2, respectively. Although further experimental validation of these candidate genes is required, several appear to be involved in growth and developmental processes related to the respective agronomic traits when compared with their homologs in Arabidopsis thaliana. This study supports the usefulness of association studies and provides valuable data for functional markers and investigating candidate genes within a diverse germplasm collection in future breeding programs.

Dataset Information

Dimensional Traits of Schizotypy Associated With Glycine Receptor GLRA1 Polymorphism: An Exploratory Candidate-Gene Association Study.

Publications

Dimensional Traits of Schizotypy Associated With Glycine Receptor GLRA1 Polymorphism: An Exploratory Candidate-Gene Association Study.

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