Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of schizophrenia genetics has confirmed the importance of genes in etiology, but has not so far identified the relationship between observed genetic risks and specific DNA variants, protein alterations or biological processes. In spite of many limitations, numerous regions of the human genome give consistent, although by no means unanimous, support for linkage, which is unlikely to occur by chance. Two recent shifts have been evident in the field. First, a series of studies combining linkage and association analyses in the same family sets have identified promising candidate genes (DTNBP1, NRG1, G72/G30, TRAR4). Although a consensus definition of replication for genetic association in a complex trait remains difficult to achieve, the evidence for two of these (dystrobrevin binding protein 1 (DTNBP1), NRG1) is strong. Second, a series of studies combining association with functional investigation of changes in the associated gene in schizophrenia have also identified several candidate genes (COMT, RGS4, PPP3CC, ZDHHC8, AKT1). Somewhat surprisingly, the loci implicated by these studies have proven less robust in replication, although the number of replication studies remains small in several cases. Assessment of the combined evidence for the DTNBP1 gene gives some insight into the nature of the problems remaining to be solved.
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PMID:Molecular genetic studies of schizophrenia. 1672 3

Genetic variations in G72/G30 have been reported to be associated with schizophrenia and bipolar disorders in several case-control studies. This gene is located in a genomic region known to contain susceptibility genes for schizophrenia. As case-control studies carry an increased risk of confounding through population stratification, we investigate whether the rs947267 (A/C) polymorphism is associated with schizophrenia in a family-based association study. This polymorphism is located within the G72/G30 gene and has been previously associated with bipolar disorders. The sample consisted of a total of 216 Chinese families that included an affected offspring and parents. Transmission disequilibrium analysis revealed a significant association between the G72/G30 rs947267 polymorphism and schizophrenia (P=0.016), with the A allele more commonly transmitted to patients. Further analysis stratified by sex showed that the A allele was significantly more overtransmitted than nontransmitted in the trios of male probands (P=0.031), but not in the trios of female probands. Our family-based association study supports the suggestion that the G72/G30 gene may be implicated in susceptibility to schizophrenia and there may be an interaction between this gene and sex in the pathogenesis of schizophrenia.
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PMID:Family-based association study between G72/G30 genetic polymorphism and schizophrenia. 1679 Nov 5

In follow-up from evidence obtained in linkage studies, systematic linkage disequilibrium mapping within chromosomal region 13q33 has led to the identification of a schizophrenia susceptibility locus which harbors the genes G72 and G30. These association findings have been replicated in several independent schizophrenia samples. Association has also been found between genetic variants at the G72/G30 locus and bipolar affective disorder (BPAD), with replication in independent studies. Results from studies of more detailed psychiatric phenotypes show that association exists with symptom clusters that are common to several disorders as well as with specific psychiatric diagnoses. These findings may indicate that the association lies not with the diagnostic categories per se but with more specific aspects of the phenotype, such as affective symptoms and cognitive effects, which cross traditional psychiatric diagnostic boundaries. At the molecular level, the picture remains far from clear. No putative functional variants have been identified in the coding regions of G72 or G30, and it is therefore likely that disease susceptibility is caused by as yet unidentified variants which alter gene expression or splicing. A further complication is the fact that inconsistencies are evident in the risk alleles and haplotypes observed to be associated across different samples and studies, which may suggest the presence of multiple susceptibility variants at this locus. Functional analyses indicate that the G72 gene product plays a role in the activation of N-methyl-D-aspartate receptors, a molecular pathway implicated in both schizophrenia and BPAD, making it the most plausible candidate gene at this locus.
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PMID:The G72/G30 gene locus in psychiatric disorders: a challenge to diagnostic boundaries? 1691 40

Altered glutamatergic neurotransmission is considered a potential etiological factor of schizophrenia (SCZ) and affective disorders. The gene ASCT1 (SLC1A4) coding for a Na+-dependent neutral aminoacid transporter is a member of the glutamate transporter superfamily and is located on 2p13-14, a region showing linkage to both SCZ and bipolar disorder (BD). ASCT1 can thus be considered a candidate gene for both disorders. In a German sample, we tested for association between ASCT1 and both SCZ and BD. Allele and haplotype frequencies, however, did not differ between cases and controls. Recent findings on the associations between brainderived neurotrophic factor (BDNF) and SCZ and between G72/G30 and BD suggest that SCZ patients with a history of major depressive episodes (MDE) outside psychotic episodes and BD cases with a history of persecutory delusions constitute genetically distinct subgroups of these disorders. Thus, we hypothesized that restricting case definition to those 95 SCZ individuals with MDE and to those 107 BD patients with a history of persecutory delusions might clarify the relationship between BD, SCZ and ASCT1. However, these stratification approaches did not yield any significant association either. Allele and haplotype frequencies did not differ between cases and controls. Our results do not support an association of the ASCT1 gene with BD or SCZ in the German population.
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PMID:No association between genetic variants at the ASCT1 gene and schizophrenia or bipolar disorder in a German sample. 1710 22

Schizophrenia may result from a neurotransmission hypofunction of glutamatergic and N-methyl-d-aspartate (NMDA) receptors. Linkage disequilibrium mapping has identified several promising and novel positional candidates, including the G72/G30 and d-amino-acid oxidase (DAAO) genes. Since the first positive association report, many subsequent studies have attempted to replicate the association but the results have been mixed. To try to resolve this inconsistency and to elucidate the relationship between the important glutamate-related genes and schizophrenia, the current meta-analysis has combined samples involving 16 polymorphisms covering all published case-control and family-based association studies up to October 2005. The results suggest that there is weak evidence of association between the G72/G30 genes and schizophrenia.
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PMID:G72/G30 genes and schizophrenia: a systematic meta-analysis of association studies. 1717 78

To explore the effect of G72/G30 polymorphisms on the clinical manifestations of schizophrenia, especially on the age at onset and sex of patients, we examined three single nucleotide polymorphisms in 216 schizophrenic patients and 321 healthy controls. Significant associations of schizophrenia with the A allele of rs947267 (P=0.012) and haplotype A-A-G (rs2391191-rs947267-rs778294) (P=0.008) were found in early-onset schizophrenic patients. So did the same allele (P=0.034) and haplotype (P=0.009) as mentioned above in male patients. These findings suggest that the G72/G30 gene may modulate the age at onset and there might be a potential interaction between this locus and sex in the pathogenesis of schizophrenia.
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PMID:Association of G72/G30 polymorphisms with early-onset and male schizophrenia. 1717 66

Several putative schizophrenia susceptibility genes have recently been reported, but it is not clear whether these genes are associated with schizophrenia in general or with specific disease subtypes. In a previous study, we found an association of the neuregulin 1 (NRG1) gene with non-deficit schizophrenia only. We now report an association study of four schizophrenia candidate genes in patients with and without deficit schizophrenia, which is characterized by severe and enduring negative symptoms. Single-nucleotide polymorphisms (SNPs) were genotyped in the DTNBP1 (dysbindin), G72/G30 and RGS4 genes, and the relatively unknown PIP5K2A gene, which is located in a region of linkage with both schizophrenia and bipolar disorder. The sample consisted of 273 Dutch schizophrenia patients, 146 of whom were diagnosed with deficit schizophrenia and 580 controls. The strongest evidence for association was found for the A-allele of SNP rs10828317 in the PIP5K2A gene, which was associated with both clinical subtypes (P = 0.0004 in the entire group; non-deficit P = 0.016, deficit P = 0.002). Interestingly, this SNP leads to a change in protein composition. In RGS4, the G-allele of the previously reported SNP RGS4-1 (single and as part of haplotypes with SNP RGS4-18) was associated with non-deficit schizophrenia (P = 0.03) but not with deficit schizophrenia (P = 0.79). SNPs in the DTNBP1 and G72/G30 genes were not significantly associated in any group. In conclusion, our data provide further evidence that specific genes may be involved in different schizophrenia subtypes and suggest that the PIP5K2A gene deserves further study as a general susceptibility gene for schizophrenia.
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PMID:The PIP5K2A and RGS4 genes are differentially associated with deficit and non-deficit schizophrenia. 1741 Jun 40

Several studies examining the association between G72/G30 polymorphisms and schizophrenia in cohorts of various ethnic origins have recently been reported. The aim of the current study was to examine the genetic influence of the G72/G30 polymorphisms in the Korean population. Nine G72/G30 single-nucleotide polymorphisms (SNPs) were genotyped in 388 patients with schizophrenia and 367 normal controls from the Korean population. Based on statistical analyses, the positive associations of previous studies of other populations were not replicated in the present study. However, 2 of the 9 tested SNPs, rs778294 and rs947267, were found to be associated with the risk of schizophrenia after correction for multiple testing (P(cor)=0.03 and P(cor)=0.04, respectively). The rs778294 SNP, taken singly, had not been found to be associated with schizophrenia in previous studies, and the second SNP, rs947267, showed an opposite direction of genetic effect on schizophrenia risk here than in a previous study. Our association results were not consistent with those found in other populations, and, thus could be chance findings. Therefore, further studies with larger sample sizes are needed to confirm a risk allele for this gene if it exists.
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PMID:Association analysis of G72/G30 polymorphisms with schizophrenia in the Korean population. 1765 42

The G72/G30 gene complex (G72 also known as D-amino acid oxidase activator, DAOA) and its chromosomal region 13q32-34 have been linked and associated with both schizophrenia (SCZ) and bipolar disorder (BP) in multiple studies, including our initial association report on BP. However, the inconsistency of associated variants across studies is obvious. Previous meta-analyses had small data sets. The present meta-analysis combined 18 association articles published before April of 2007. There were 19 independent studies of SCZ, with 4304 cases, 5423 controls, and 1384 families, and four independent studies of BP with 1145 cases, 1829 controls, and 174 families. Of 15 single nucleotide polymorphisms (SNPs) analyzed in the 95-kb G72/G30 gene region, M18/rs947267 and M22/rs778293 showed association with SCZ in Asians, and M24/rs1421292 with SCZ in Europeans. The associations of C allele at M18 and A allele at M22 with SCZ in Asians survived conservative Bonferroni correction for multiple testing for 15 markers and subgroup analysis (adjusted P=0.0000253 for M18; adjusted P=0.009 for M22). No single maker showed evidence of overall association with BP. These results suggest that G72/G30 may influence susceptibility to schizophrenia with weak effects.
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PMID:Allelic association of G72/G30 with schizophrenia and bipolar disorder: a comprehensive meta-analysis. 1802 49

The familial-genetic relationship between affective and schizophrenic disorders is receiving a re-emergence of interest. The reasons are a series of cross-diagnostic molecular-genetic discoveries: specific alleles in the genes for dysbindin (DTNBP1), neuregulin (NRG1) and DAOA (G72/G30) reveal associations for each of both groups of disorders in the same direction in some but not all reported studies. These findings cannot just be false positives because of confirming metaanalyses. Furthermore there is some pathophysiological support: the mentioned genes are involved in biochemical pathways, which are contributing to both disorders partly in a similar and partly in a different manner. The new levels of evidence enrich the classical continuity/discontinuity debate on the relationship between both groups of disorders.
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PMID:Common risk genes for affective and schizophrenic psychoses. 1851 16


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