Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Several linkage studies support a susceptibility locus for schizophrenia on chromosome 8p21-22. In this study, we investigated a gene mapping to 8p21, dihydropyrimidinase-like 2 (DPYSL2). DPYSL2 plays an important role in axonal formation and dysfunction of DPYSL2 may result in neurodevelopmental abnormalities. In previous studies, the expression of the gene has been shown to display alteration in the brain of schizophrenia patients compared with those of healthy controls. Recently, Nakata and colleagues found polymorphisms in the 3'-end of DPYSL2 to be associated with schizophrenia, especially the paranoid type, in a Japanese population. In this study, we genotyped four SNPs in DPYSL2 in 2552 Chinese Han specimens. Case-control and TDT analyses were performed to detect association of DPYSL2 with schizophrenia. However, no allele, genotype or haplotype association was found. We investigated the expression of DPYSL2 in 29 schizophrenia patients and 54 healthy controls using quantitative real-time PCR and no difference was found between the two groups. In a comparative allele-specific expression test, we used two SNPs as markers. Only a small proportion of heterozygotes revealed a significant difference (>20%) in allele representation. The results indicated the mRNA level did not contribute mainly in the altered expression of the gene in schizophrenia patients. Although our results provided no evidence for DPYSL2 itself as a susceptibility gene for schizophrenia, recent findings have indicated that DPYSL2 may interact with other candidate genes for schizophrenia and be worthy of further studies.
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PMID:An investigation of the dihydropyrimidinase-like 2 (DPYSL2) gene in schizophrenia: genetic association study and expression analysis. 1632 Nov 70

The interleukin-10 (IL-10) gene has been identified as a susceptibility gene for schizophrenia in Caucasians. A previous case-control study conducted by our group revealed a weak association between polymorphism, -592C/A, of the IL-10 gene promoter and schizophrenia. Our present study was aimed at confirming the association of the IL-10 promoter with schizophrenia using 197 Han Chinese sib-pair families. A family-based association test (FBAT) and haplotype analysis was undertaken using the FBAT v1.5.5. The global TDT was significant for a different polymorphism, -1082G/A (chi2=13.16, P=0.000285) and that the allele -1082G was preferentially transmitted to schizophrenia-affected children. Furthermore, haplotype TDT analysis showed that haplotype "GCC" was significantly associated with the disease (chi2=8.1, P=0.00443). Our results also indicate that the IL-10 gene may play a significant role in the etiology of schizophrenia among Han Chinese.
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PMID:Interleukin-10 -1082 promoter polymorphism is associated with schizophrenia in a Han Chinese sib-pair study. 1637 87

The RTN4R gene is located in the 22q11 region and it encodes a subunit of the receptor complex (RTN4R-p75NTR) which results in neuronal growth inhibitory signals in response to Nogo-66, MAG or OMG signaling. Previous studies have suggested that RTN4R might act as a potential candidate for schizophrenia susceptibility loci. We genotyped four SNPs within the gene and conducted a case-control study and TDT analysis, involving 707 schizophrenic patients, 689 controls and 372 unrelated small nuclear families with schizophrenic offspring in the Chinese population. We examined allele and genotype frequencies and haplotype distributions in both family- and nonfamily-based samples. Our results suggest that there is no significant association between the genetic polymorphisms and schizophrenia in the Han Chinese population.
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PMID:No association between the genetic polymorphisms in the RTN4R gene and schizophrenia in the Chinese population. 1689 6

The genetic basis of bipolar disorder (BPD) and schizophrenia (SCZ) has been established through numerous clinical and molecular studies. Although often considered separate nosological entities, evidence now suggests that the two syndromes may share some genetic liability. Recent studies have used a composite phenotype (psychosis) that includes BPD, SCZ, psychosis not otherwise specified, and schizoaffective disorder, to identify shared susceptibility loci. Several chromosomal regions are reported to be shared between these syndromes (18p, 6q, 10p, 13q, 22q). As a part of our endeavor to scan these regions, we report a positive linkage and association finding at 18p11.2 for psychosis. Two-point linkage analysis performed on a series of 52 multiplex pedigrees with 23 polymorphic markers yielded a LOD score of 2.02 at D18S37. An independent set of 159 parent offspring trios was used to confirm this suggestive finding. The TDT analysis yielded support for association between the marker D18S453 and the disease allele (chi2 = 4.829, P < 0.028). This region has been implicated by several studies on BPD [Sjoholt et al. (2004); Mol Psychiatry 9(6):621-629; Washizuka et al. (2004); Biol Psychiatry 56(7):483-489; Pickard et al. (2005); Psychiatr Genet 15(1):37-44], SCZ [Kikuchi et al. (2003); J Med Dent Sci 50(3):225-229; Babovic-Vuksanovic et al. (2004); Am J Med Genet 124(3):318-322] and also as a shared region between the two diseases [Ishiguro et al. (2001); J Neural Transm 108(7):849-854; Reyes et al. (2002); Mol Psychiatry 7(4):337-339; Craddock et al. (2005); J Med Genet 42(3):193-204]. Our findings provide an independent validation of the above reports, and suggest the presence of susceptibility loci for psychoses in this region.
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PMID:Evidence of linkage and association on 18p11.2 for psychosis. 1694 53

Neuregulin 1 (NRG1) is one of the most exciting candidate genes for schizophrenia since its first association with the disorder in an Icelandic population. Since then, many studies have analyzed allele and haplotype frequencies in European and Asian populations in cases and controls yielding varying results. We investigated the association of NRG1 with psychosis in a total sample set of 575 individuals from 151 Spanish nuclear families. We tested eight SNPs across 1.2 Mb along NRG1 including regions previously associated to schizophrenia in association studies. After correction for multiple testing, the TDT analysis for each marker did not show a significant over-transmission of alleles from the parents to the affected offspring for any of the markers (P > 0.05). The haplotypic analysis with TRANSMIT and PDT did not show preferential transmission for any of the haplotypes analyzed in our sample. These results do not seem to suggest that the investigated NRG1 markers play a role in schizophrenia in the Spanish population, although the finding of a trend for association with one SNP in the 3'of the gene warrants further investigation.
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PMID:Family-based association study of neuregulin-1 gene and psychosis in a Spanish sample. 1750 51

Several lines of evidence have suggested an interesting link between gluten ingestion and schizophrenia. Increased levels of gliadin antibodies have been observed in patients with schizophrenia. Tissue transglutaminase (transglutaminase 2, TGM2) is involved in the production of gliadin antibodies. To investigate genetic association of the TGM2 gene with schizophrenia, we detected eight single nucleotide polymorphisms (SNPs) present in the gene among 131 family trios composed of fathers, mothers and affected offspring with schizophrenia. Data analysis with the UNPHASED program showed allelic association for rs2076380 (chi(2) = 5.51, P = 0.019), rs7270785 (chi(2) = 8.13, P = 0.004), rs4811528 (chi(2) = 6.13, P = 0.013) and rs6023526 (chi(2) = 6.13, P = 0.013). The global P-value was 0.029 for 10,000 permutations with the TDT analysis. The strongest association was observed for the rs7270785-rs4811528 haplotypes (chi(2) = 16.18, df = 3, P = 0.001), and the global P-value was 0.008 for 10,000 permutations with the 2-SNP haplotype analysis. The 8-SNP haplotype analysis also revealed a strong haplotypic association (chi(2) = 44.82, df = 18, P = 0.0004) and the 1-df test showed that the A-T-A-A-T-G-A-G haplotype was excessively transmitted (chi(2) = 16.98, corrected P = 0.0007). The present results suggest that the TGM2 gene may be involved in the development of schizophrenia.
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PMID:The TGM2 gene is associated with schizophrenia in a British population. 1856 Dec 61

A number of genes located on chromosome 22q11-13, including catechol-O-methyltransferase (COMT), are potential schizophrenia susceptibility genes. Recently, the sulfotransferase-4A1 (Sult4A1) locus within chromosome 22q13 was reported to be linked to schizophrenia in a family TDT study. Sult4A1 is related to metabolism of monoamines, particularly dopamine and norepinephrine, both of which have been implicated in the pathophysiology of the psychopathology and cognitive dysfunction components of schizophrenia. An available, prospectively collected data base was interrogated to determine how three Sult4A1 SNPs: rs138060, rs138097, and rs138110, previously shown to be associated with schizophrenia might be associated with psychopathology, cognition, and quality of life in a sample of 86 Caucasian patients with schizophrenia or schizoaffective disorder. The majority of patients met criteria for treatment resistant schizophrenia and had been drug-free for one week or longer at the time of evaluation. The major findings were: 1) patients heterozygous (T/G) for rs138060 had significantly worse Brief Psychiatric Rating Scale (BPRS) Total and anxiety/depression sub-scale scores, and higher Scale for the Assessment of Positive Symptoms (SAPS) Total scores than G/G homozygous patients; and 2) patients heterozygous (A/G) for rs138097 demonstrated significantly worse performance on neuropsychological testing, specifically on tests of executive function and working memory, compared to patients homozygous for the G and A alleles. RS138110 was unrelated to psychopathology and cognition. These results provide the first evidence of how genetic variation in Sult4A1 may be related to clinical symptoms and cognitive function in schizophrenia, and permit future studies to attempt to replicate these potentially important findings.
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PMID:Association of Sult4A1 SNPs with psychopathology and cognition in patients with schizophrenia or schizoaffective disorder. 1882 57

Schizophrenia has been observed to be associated with various abnormalities in cytokines and cytokine receptors that have been one of the recent focal points of immunological research in schizophrenia. Recent reports have showed that IL-3 gene, colony stimulating factor 2 receptor alpha (CSF2RA) and IL-3 receptor alpha (IL3RA) are associated with schizophrenia. The aim of this study was to investigate IL3RA gene variants in schizophrenia among a Chinese population by using a family-based association approach. Our sample included 101 Chinese parent-offspring trios of Han descent. All subjects were genotype for IL3RA-rs6603272 and -rs6645249 using PCR techniques. Single marker analysis showed a significant association for rs6603272 (X(2)=5.15, df=1, P=0.023), but not for the rs6645249. However, there was a significant genotypic association of both the polymorphisms with schizophrenia (for rs6603272, X(2)=6.15, df=2, P=0.046; for rs6645249, X(2)=21.79, df=2, P=1.85e-005). Haplotype TDT was statistically significant (X(2)=5.14, df=1, P=0.023), with the rs6603272(T)-rs6645249(G) haplotype significantly associated with schizophrenia (OR=1.66; 95% CI=1.08-2.55). In conclusion, our family-based association study also revealed a small but significant contribution of the IL3RA variants to susceptibility to schizophrenia in a Chinese population.
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PMID:A family-based study of the IL3RA gene on susceptibility to schizophrenia in a Chinese Han population. 1928 3

A common approach to genetic mapping of loci for complex diseases is to perform a genome-wide association study (GWAS) by analyzing a vast number of SNP markers in cohorts of unrelated cases and controls. A direct motivation for the case-control design is that unrelated, affected individuals can be easier to collect than large families with multiple affected persons in the Western world. Despite its higher potential power, investigators have not actively pursued family ascertainment in part because of a dearth of methods for analyzing such correlated data on a large scale. We examine the statistical properties of several commonly used family-based association tests, as to their performance using real-life mixtures of families and singletons taken from our own migraine and schizophrenia studies, as well as population-based data for a complex trait simulated with the evolutionary phenogenetic simulator, ForSim. In virtually every situation, the full likelihood-based methods in the PSEUDOMARKER program outperformed those implemented in FBAT, GENEHUNTER TDT, PLINK (family-based options), HRR/HHRR, QTDT, TRANSMIT, UNPHASED, MENDEL, and LAMP. We further show that GWAS is much more powerful when family samples are used rather than unrelateds, on a genotype-by-genotype basis.
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PMID:On the statistical properties of family-based association tests in datasets containing both pedigrees and unrelated case-control samples. 2193 7

Although the association of common genetic variation in the extended MHC region with schizophrenia is the most significant yet discovered, the MHC region is one of the more complex regions of the human genome, with unusually high gene density and long-range linkage disequilibrium. The statistical test on which the MHC association is based is a relatively simple, additive model which uses logistic regression of SNP genotypes to predict case-control status. However, it is plausible that more complex models underlie this association. Using a well-characterized sample of trios, we evaluated more complex models by looking for evidence for: (a) non-random mating for HLA alleles, schizophrenia risk profiles, and ancestry; (b) parent-of-origin effects for HLA alleles; and (c) maternal-fetal genotype incompatibility in the HLA. We found no evidence for non-random mating in the parents of individuals with schizophrenia in terms of MHC genotypes or schizophrenia risk profile scores. However, there was evidence of non-random mating that appeared mostly to be driven by ancestry. We did not detect over-transmission of HLA alleles to affected offspring via the general TDT test (without regard to parent of origin) or preferential transmission via paternal or maternal inheritance. We evaluated the hypothesis that maternal-fetal HLA incompatibility may increase risk for schizophrenia using eight classical HLA loci. The most significant alleles were in HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 but none was significant after accounting for multiple comparisons. We did not find evidence to support more complex models of gene action, but statistical power may have been limiting.
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PMID:Non-random mating, parent-of-origin, and maternal-fetal incompatibility effects in schizophrenia. 2317 29


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