| GABRR1 |
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| 1 | | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Oct 153B: 1347-9 |
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| PMID | 20583128 |
| Title | Variation at the GABAA receptor gene, Rho 1 (GABRR1) associated with susceptibility to bipolar schizoaffective disorder. |
| Abstract | We have previously reported evidence that variation at GABA(A) receptor genes is associated with susceptibility to bipolar disorder with schizophrenia-like psychotic features (Research Diagnostic Criteria (RDC) schizoaffective disorder, bipolar type) with gene-wide significance at GABRB1, GABRA4, GABRB3, GABRA5, and GABRR3. Here we provide suggestive evidence implicating a sixth member of the gene family, GABRR1 (gene-wide P?=?0.0058; experiment-wide corrected significance P?=?0.052). |
| SCZ Keywords | schizophrenia |
| 2 | | Schizophr. Res. 2010 Dec 124: 192-9 |
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| PMID | 20889312 |
| Title | A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. |
| Abstract | Schizophrenia and bipolar disorder both have strong inherited components. Recent studies have indicated that schizophrenia and bipolar disorder may share more than half of their genetic determinants. In this study, we performed a meta-analysis (combined analysis) for genome-wide association data of the Affymetrix Genome-Wide Human SNP array 6.0 to detect genetic variants influencing both schizophrenia and bipolar disorder using European-American samples (653 bipolar cases and 1034 controls, 1172 schizophrenia cases and 1379 controls). The best associated SNP rs11789399 was located at 9q33.1 (p=2.38 × 10(-6), 5.74 × 10(-4), and 5.56 × 10(-9), for schizophrenia, bipolar disorder and meta-analysis of schizophrenia and bipolar disorder, respectively), where one flanking gene, ASTN2 (220kb away) has been associated with attention deficit/hyperactivity disorder and schizophrenia. The next best SNP was rs12201676 located at 6q15 (p=2.67 × 10(-4), 2.12 × 10(-5), 3.88 × 10(-8) for schizophrenia, bipolar disorder and meta-analysis, respectively), near two flanking genes, GABRR1 and GABRR2 (15 and 17kb away, respectively). The third interesting SNP rs802568 was at 7q35 within CNTNAP2 (p=8.92 × 10(-4), 1.38 × 10(-5), and 1.62 × 10(-7) for schizophrenia, bipolar disorder and meta-analysis, respectively). Through meta-analysis, we found two additional associated genes NALCN (the top SNP is rs2044117, p=4.57 × 10(-7)) and NAP5 (the top SNP is rs10496702, p=7.15 × 10(-7)). Haplotype analyses of above five loci further supported the associations with schizophrenia and bipolar disorder. These results provide evidence of common genetic variants influencing schizophrenia and bipolar disorder. These findings will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in schizophrenia and bipolar disorder. |
| SCZ Keywords | schizophrenia |
| 3 | | Schizophr. Res. 2014 Aug 157: 163-8 |
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| PMID | 24893910 |
| Title | Effect of antipsychotic drugs on gene expression in the prefrontal cortex and nucleus accumbens in the spontaneously hypertensive rat (SHR). |
| Abstract | Antipsychotic drugs (APDs) are the standard treatment for schizophrenia. The therapeutic effect of these drugs is dependent upon the dopaminergic D2 blockade, but they also modulate other neurotransmitter pathways. The exact mechanisms underlying the clinical response to APDs are not fully understood. In this study, we compared three groups of animals for the expression of 84 neurotransmitter genes in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Each group was treated with a different APD (risperidone, clozapine or haloperidol), and with a non-treated group of spontaneously hypertensive rats (SHRs), which is an animal model for schizophrenia. This study also explored whether or not differential expression was regulated by DNA methylation in the promoter region (PR). In the clozapine group, we found that Chrng was downregulated in the NAcc and six genes were downregulated in the PFC. In the haloperidol group, Brs3 and Glra1 were downregulated, as was Drd2 in the clozapine group and Drd3, Galr3 and Gabrr1 in the clozapine and haloperidol groups. We also encountered four hypermethylated CG sites in the Glra1 PR, as well as three in the risperidone group and another in the haloperidol group, when compared to non-treated rats. Following the APD treatment, the gene expression results revealed the involvement of genes that had not previously been described, in addition to the activity of established genes. The investigation of the involvement of these novel genes can lead to better understanding about the specific mechanisms of action of the individual APDs studied. |
| SCZ Keywords | schizophrenia |
