1Schizophr. Res. 2010 Dec 124: 192-9
PMID20889312
TitleA genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.
Abstractschizophrenia 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 Keywordsschizophrenia
2Psychiatry Res 2013 Dec 210: 1290-2
PMID24113126
TitleNeurotransmitter receptor and regulatory gene expression in peripheral blood of Brazilian drug-nave first-episode psychosis patients before and after antipsychotic treatment.
AbstractLittle is known about how genes expressed in blood relate to schizophrenia or antipsychotic use. We analyzed gene expression in 10 first-episode psychosis patients and nine controls using PCR Arrays. GABRR2 and CHRNA3 were found to be differentially expressed after risperidone treatment. These genes may be regulated by antipsychotic use.
SCZ Keywordsschizophrenia
3J Psychiatr Res 2014 Sep 56: 130-6
PMID24935901
TitleEvaluation of neurotransmitter receptor gene expression identifies GABA receptor changes: a follow-up study in antipsychotic-nave patients with first-episode psychosis.
AbstractA study of the gene expression levels in the blood of individuals with schizophrenia in the beginning of the disease, such as first-episode psychosis (FEP), is useful to detect gene expression changes in this disorder in response to treatment. Although a large number of genetic studies on schizophrenia have been conducted, little is known about the effects of antipsychotic treatment on gene expression. The aim of the present study was to examine differences in the gene expression in the blood of antipsychotic-nave FEP patients before and after risperidone treatment (N = 44) and also to verify the correlation with treatment response. In addition, we determined the correlations between differentially expressed genes and clinical variables. The expression of 40 neurotransmitter and neurodevelopment-associated genes was assessed using the RT2 Profiler PCR Array. The results indicated that the GABRR2 gene was downregulated after risperidone treatment, but no genes were associated with response to treatment and clinical variables after Bonferroni correction. GABRR2 downregulation after treatment can both suggest an effect of risperidone treatment or processes related to disease progression, either not necessarily associated with the improvement of symptoms. Despite this change was observed in blood, this decrease in GABRR2 mRNA levels might be an effect of changes in GABA concentrations or other systems interplay consequently to D2 blockage induced by risperidone, for example. Thus, it is important to consider that antipsychotics or the progression of psychotic disorders might interfere with gene expression.
SCZ Keywordsschizophrenia