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 NOTCH4 gene was recently reported to be associated with schizophrenia based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls.
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PMID:Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland. 1138 Dec 58

Several lines of research indicate a cholecystokinin (CCK) deficit in schizophrenia patients. A C to T substitution was found in the promoter region of the CCK gene. We investigated this promoter variant in patients with schizophrenia and geographically-matchedcontrols. The T allele was detected in 24% of the 85 schizophrenics and 16% of the 247 controls. No significant difference in the T allele frequency was found between patients and controls (chi(2) = 2.77, P > 0.1). The schizophrenia sample was analyzed further along the dimensions of positive and negative symptoms. The patients with prominent negative symptoms presented a statistically significant association to the T allele (chi(2) = 4.13, P < 0.04). However, the significance disappeared after the Bonferroni correction (P > 0.15). Since the case-control analysis may present incorrect ethnic match between cases and controls, we applied the family-based tests to verify the above findings. Both transmission disequilibrium test (TDT; chi(2) = 5.33, P < 0.025 in 12 trios) and haplotype relative risk (HRR; chi(2) = 3.844, P < 0.05 in 60 trios) indicated a significantly high transmission of T allele to schizophrenia offspring probands from their parents. While our family-based tests seem to support the CCK involvement in schizophrenia, no definite conclusion can be drawn based on such a small sample size. This preliminary finding is subjected to future investigations.
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PMID:Possible association of a cholecystokinin promoter variant to schizophrenia. 1211 80

We examined whether variation within six genes from the VCFS critical region at 22q11 (DGSC, Stk22A1, DGSI, Gscl, Slc25A1 and Znf74) confers susceptibility to schizophrenia. We screened the exons and flanking intronic sequence of each gene for mutations in 14 individuals with DSM-IV schizophrenia using DHPLC. All polymorphisms identified were characterised and genotyped in a sample of 184 schizophrenics and matched controls, using novel DNA pooling methods. Of the polymorphisms identified, 17 were located within exons, six were within coding sequence, and two were non-synonymous. Pooled genotyping revealed no differences in the allele frequencies for any polymorphism between cases and controls that met our pre-defined criterion (P < or = 0.1). In a complementary approach we also attempted to define the location of a schizophrenia susceptibility locus more precisely by performing association mapping using seven microsatellites spanning the VCFS region with an average inter-marker distance of 450 kb. Conventional chi(2) analysis of genotypes in 368 cases and 368 controls revealed that none of the markers was significantly associated (P < 0.05) with schizophrenia. However, evidence for significant association (P = 0.003) was obtained for D22S944 when alleles were combined. TDT analysis of D22S944 genotyped in a further 278 cases of schizophrenia and their parents failed to find any overall allele-wise significant transmission disequilibrium (chi(2) = 18.3, P = 0.17). However, individual analysis of the alleles revealed that allele 12 was excessively non-transmitted and that this almost reached significance when corrected for multiple alleles (chi(2) = 7.35, P = 0.006, P = 0.078 corrected for 13 alleles).
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PMID:Mutation screening and LD mapping in the VCFS deleted region of chromosome 22q11 in schizophrenia using a novel DNA pooling approach. 1247 24

COMT is a ubiquitous enzyme crucial to catechol metabolism. The molecular basis of COMT thermolability, that leads to three to fourfold differences in enzyme activity, is due to a substitution of valine with methionine in the Val158/108Met polymorphism. Of special interest is the role of this gene in major psychoses especially since a microdeletion (22q11) containing the COMT gene (velo-cardio-facial syndrome) also carries with it several types of behavioral disorders, including an increased prevalence of schizophrenia. Almost 20 genetic studies have examined the role of COMT in schizophrenia with ambiguous results. Towards clarifying the role of this polymorphism in conferring risk for psychosis, we examined a large group of culturally and ethnically akin Palestinian Arab schizophrenic triads (N = 276) using both a case-control and family-based study. In 194 informative triads with at least one heterozygote parent, no preferential transmission of either COMT allele was observed in this sample (TDT statistic chi-square = 0.14 NS; 131 COMT valine alleles were transmitted and 125 alleles not transmitted). However, using a case-control design a significant increase (Likelihood ratio = 3.935, P = 0.047) in the valine allele was observed in the group of schizophrenic patients (N = 276) compared to an ethnically matched control group (N = 77). The association was stronger in female patients (P = 0.012) similar to other studies showing that some COMT behavioral effects are gender sensitive. In summary, by case-control design but not by a family-based study, there is a weak effect in female patients of the high activity COMT allele in conferring risk for schizophrenia.
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PMID:Family-based and case-control study of catechol-O-methyltransferase in schizophrenia among Palestinian Arabs. 1270 35

We report here on the detection of nine single nucleotide polymorphisms (SNPs) near to the NOTCH4 locus in the search for schizophrenia susceptibility genes in the class III region of the human major histocompatibility complex (MHC). We totally analyzed 122 family trios recruited in the UK. The TDT analysis demonstrated that of the nine SNPs, three were associated with schizophrenia, including rs1009382 (P = 0.00047), rs204887 (P = 0.007), and rs8283 (P = 0.015). Both rs1009382 and rs204887 are present in the TNXB locus. The rs1009382 is a non-synonymous SNP located in exon 23 of the gene and its A to G base change causes a Glu2578Gly substitution. The goodness-of-fit test showed that genotypic distribution of rs1009382 was deviated from Hardy-Weinberg equilibrium due to homozygote excess in the patient group (P = 0.01), suggesting that a double dose of a genetic risk may be involved. Possibly, rs1009382 is a candidate SNP predisposing to a schizophrenic illness. Moreover, the test for linkage disequilibrium (LD) between paired SNPs showed that the nine SNPs studied may be in the same LD block with an unexpected pattern as the strength of LD was not correlated with the distance between paired SNPs. The haplotype analysis suggested that there might be more than one disease-related allele located in the class III region of the MHC, and that these alleles possibly confer either susceptibility or resistance to schizophrenia.
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PMID:TNXB locus may be a candidate gene predisposing to schizophrenia. 1475 42

Postmortem brain studies have shown deficits in the cortical gamma-aminobutyric acid (GABA) system in schizophrenic individuals. Expression studies have shown a decrease in the major GABA-synthesizing enzyme (glutamic acid decarboxylase (GAD67) mRNA levels in neurons in dorsolateral prefrontal cortex in schizophrenics relative to controls. In the present study, SNPs in and around the GAD1 gene, which encodes the protein GAD67, were tested on a rare, severely ill group of children and adolescents with childhood-onset schizophrenia (COS) (n=72), in a family-based association analysis. Compared to adult-onset samples, the COS sample has evidence for more salient familial, and perhaps genetic, risk factors for schizophrenia, as well as evidence for frontal cortical hypofunction, and greater decline in cortical gray matter volume on anatomic brain MRI scans during adolescence. We performed family-based TDT and haplotype association analyses of the clinical phenotype, as well as association analyses with endophenotypes using the QTDT program. Three adjacent SNPs in the 5' upstream region of GAD1 showed a positive pairwise association with illness in these families (P=0.022-0.057). Significant transmission distortion of 4-SNP haplotypes was also observed (P=0.003-0.008). Quantitative trait TDT analyses showed an intriguing association between several SNPs and increased rate of frontal gray matter loss. These observations, when taken together with the positive results reported recently in two independent adult-onset schizophrenia pedigree samples, suggest that the gene encoding GAD67 may be a common risk factor for schizophrenia.
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PMID:GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. 1550 39

Recently, proteolipid protein 1 (PLP1) has been identified as downregulated in schizophrenia by quantitative PCR and other technologies. In this work we attempted to investigate the role of PLP1 in the etiology of schizophrenia using a family based association study in 487 Chinese Han family trios. The TDT for allelic association demonstrated that, in male, a weak association was detected in SNP rs475827 with p=0.0294, suggesting that the genetic polymorphisms within PLP1 in male are likely to confer an increased susceptibility to schizophrenia in the Chinese population.
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PMID:A family-based association study of PLP1 and schizophrenia. 1569 62

Association of the G72/G30 locus with schizophrenia was recently reported in French Canadian, Russian, and Ashkenazi populations using case-control studies. In the present study we hypothesize the existence of a G72/G30 risk allele over-transmitted to affected sibs in Palestinian Arab families. A total of 223 Palestinian Arab families that included an affected offspring and parents were genotyped with 11 SNPs encompassing the G72/G30 genes. The families were recruited from three regions of Israel: 56 from the North (Afula), 136 from the central hill region (Bethlehem, Palestinian Authority), and 31 from the South (Beersheva). Individual SNP analyses disclosed a risk allele in SNP rs3916970 by both haplotype relative risk (HRR: chi(2) = 5.59, P = 0.018) and transmission disequilibrium test (TDT: chi(2) = 6.03, P = 0.014) in the Afula families. Follow-up multilocus analysis using family-based association tests (FBAT: z = 2.197, P = 0.028) exposed the adjacent haplotype. SNP rs3916970 is located about 8 kb from the linkage disequilibrium block that was reported to be associated with schizophrenia in Ashkenazi Jews. Excess of similar haplotypes of this region was observed in the Palestinian Arabs and the Ashkenazi patients. These data suggest a common risk factor for schizophrenia susceptibility in the G72/G30 locus among Ashkenazi Jews and Palestinian Arabs. The results strengthen previous reports on the role of this locus in the etiology of schizophrenia.
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PMID:Transmission disequilibrium and haplotype analyses of the G72/G30 locus: suggestive linkage to schizophrenia in Palestinian Arabs living in the North of Israel. 1608 1

Previous studies suggest a role for chromosome 22q13 in schizophrenia. This segment of chromosome 22 contains the sulfotransferase-4A1 (Sult4A1) gene, which encodes an enzyme thought to be involved in neurotransmitter metabolism in the central nervous system. To evaluate this candidate, we developed a microsatellite marker targeting a polymorphism in its 5' nontranslated region (D22s1749E). Using samples obtained from the National Institutes of Mental Health Schizophrenia Genetics Initiative, we evaluated 27 families having multiple siblings with schizophrenia and schizophrenia-spectrum disorders for transmission disequilibrium (TDT) of this marker along with three single nucleotide polymorphisms (SNPs) spanning a 37 kb segment containing the Sult4A1 gene. TDT for D22s1749E was significant (P < 0.05), with a tendency for the 213 nt allele to be preferentially transferred to affected children (P = 0.0079). Global chi-square values for haplotypes involving the SNPs (ss146366, ss146407, and ss146420) and D22s1749E, also showed significant TDT values (P = 0.0006-0.0016). Consequently, we proposed that Sult4A merited more careful scrutiny as a candidate gene for schizophrenia susceptibility.
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PMID:Transmission disequilibrium suggests a role for the sulfotransferase-4A1 gene in schizophrenia. 1615 68

Since identification of the genetic component in anorexia nervosa (AN), genes that partake in serotonergic and dopaminergic systems and in hormonal and weight regulation have been suggested as potential candidates for AN susceptibility. We propose another set of candidate genes. Those are genes that are involved in the signaling pathway using NMDA-R and SK channels and have been suggested as possible effectors of NMDA-R driven signaling. The role of NMDA-R in the etiology of schizophrenia has already been substantiated on various levels. Several studies based on population and family groups have implicated SK3 in schizophrenia and more recently in AN as well. Our study group consisted of 90 AN family trios. We examined the transmission of two potentially functional polymorphisms, 5073T>G polymorphism in the gene encoding the NR2B subunit of NMDA-R and CAG repeats in the coding region of SK3 channel gene. Using HHRR and TDT approaches, we found that both polymorphisms were preferentially transmitted to AN offspring (TDT yielded chi(2)=5.01, p=0.025 for NR2B 5073G alleles and chi(2)=11.75, p<0.001 for SK3 L alleles including >19 repeats). Distribution analysis of the combined NR2B/SK3 genotypes suggests that the contribution of both polymorphisms to AN risk is independent and cumulative (OR=2.44 for NR2B GG genotype and OR=3.01 for SK3 SL and LL genotypes, and OR=6.8 for the combined NR2B/SK3 genotypes including high-risk alleles). These findings point to the contribution of genes associated with the NMDA-R signaling pathway to predisposition and development of AN.
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PMID:Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca(2+)-activated K+ channel to genetic predisposition to anorexia nervosa. 1615 52


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