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)

Clinical researches have shown that there is a genetic contribution to the pathogenesis of schizophrenia. Recent studies have suggested that three genes neuropeptide Y (NPY), phosphoinositide-3-kinase class 3 (PIK3C3) and 14-3-3 eta chain gene (YWHAH) are probably associated with schizophrenia. To replicate these findings, we carried out a family-based study on a sample of 235 trios. Our results suggest that the polymorphisms at the NPY and YWHAH genes are unlikely to be linked with genetic susceptibility to schizophrenia. However, we found significant evidence of preferential transmission of the -432C allele of the PIK3C3 gene in the entire trios (Z=2.91, d.f.=1, P=0.0036) and the male probands trios (Z=2.66, d.f.=1, P=0.0079).
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PMID:A family-based association study of schizophrenia with polymorphisms at three candidate genes. 1581 94

A case-control study was carried out on a sample of 583 cases vs. 372 controls in the Chinese Han population, investigating several published polymorphisms in the YWHAH and NPY genes, which reported to be associated with schizophrenia. The polymorphism -134 (GCCTGCA)2-4, in the YWHAH was not analyzed for the failure of amplification, and the polymorphism T1128C in the NPY is not existent in the samples. The analysis was then emphasized on the variants -485C > T(NPY) and G753A(YWHAH). However, no significant differences of allele frequencies (with P values of 0.696 and 0.743, OR values of 1.041 and 0.962 respectively) or genotype frequencies (with P value of 0.45 and 0.75, chi2 = 1.51 and 0.58 respectively) among the matched groups were found. No sex-dependent effect was found either. Also,the analysis of the relative risk between the genotypes of the two genes indicates that the two genes could not cooperate with each other to add the risk of disease (P > 0.05). The results suggest that the polymorphisms - 485C > T (NPY) and G753A (YWHAH) are unlikely to be linked with genetic susceptibility to schizophrenia in the Chinese Han population.
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PMID:[Association study between NPY and YWHAH gene polymorphisms and schizophrenia]. 1645 51

Bipolar disorder and schizophrenia share common chromosomal susceptibility loci and many risk-promoting genes. Oligodendrocyte cell loss and hypomyelination are common to both diseases. A number of environmental risk factors including famine, viral infection, and prenatal or childhood stress may also predispose to schizophrenia or bipolar disorder. In cells, related stressors (starvation, viruses, cytokines, oxidative, and endoplasmic reticulum stress) activate a series of eIF2-alpha kinases, which arrest protein synthesis via the eventual inhibition, by phosphorylated eIF2-alpha, of the translation initiation factor eIF2B. Growth factors increase protein synthesis via eIF2B activation and counterbalance this system. The control of protein synthesis by eIF2-alpha kinases is also engaged by long-term potentiation and repressed by long-term depression, mediated by N-methyl-D-aspartate (NMDA) and metabotropic glutamate receptors. Many genes reportedly associated with both schizophrenia and bipolar disorder code for proteins within or associated with this network. These include NMDA (GRIN1, GRIN2A, GRIN2B) and metabotropic (GRM3, GRM4) glutamate receptors, growth factors (BDNF, NRG1), and many of their downstream signaling components or accomplices (AKT1, DAO, DAOA, DISC1, DTNBP1, DPYSL2, IMPA2, NCAM1, NOS1, NOS1AP, PIK3C3, PIP5K2A, PDLIM5, RGS4, YWHAH). They also include multiple gene products related to the control of the stress-responsive eIF2-alpha kinases (IL1B, IL1RN, MTHFR, TNF, ND4, NDUFV2, XBP1). Oligodendrocytes are particularly sensitive to defects in the eIF2B complex, mutations in which are responsible for vanishing white matter disease. The convergence of natural and genetic risk factors on this area in bipolar disorder and schizophrenia may help to explain the apparent vulnerability of this cell type in these conditions. This convergence may also help to reconcile certain arguments related to the importance of nature and nurture in the etiology of these psychiatric disorders. Both may affect common stress-related signaling pathways that dictate oligodendrocyte viability and synaptic plasticity.
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PMID:eIF2B and oligodendrocyte survival: where nature and nurture meet in bipolar disorder and schizophrenia? 1732 32

YWHAH is a positional and functional candidate gene for both schizophrenia and bipolar disorder (BP). This gene has been previously shown to be associated with both disorders, and the chromosome location (22q12.3) has been repeatedly implicated in linkage studies for these disorders. It codes for the eta subtype of the 14-3-3 protein family, is expressed mainly in brain, and is involved in HPA axis regulation. We investigated the association of YWHAH with BP in a large sample, consisting of 1211 subjects from 318 nuclear families including 554 affected offspring. We tested for association with the standard BP phenotype as well as subtypes defined by psychotic and mood-incongruent features. We genotyped five tag SNPs and the (GCCTGCA)(n) polymorphic locus present in this gene. Using a family-based association test, we found that rs2246704 was associated with BP (OR 1.31, P = 0.03) and psychotic BP (OR = 1.66, P = 0.002). The polymorphic repeat and two other SNPs were also modestly associated with psychotic BP. We have provided additional evidence for association of variants in YWHAH with major mental illness. Additional association analyses of larger sample sets will be required to clarify the role of YWHAH in schizophrenia and BP. The use of clinical sub-phenotypes such as psychotic features or other potential schizophrenia/BP overlap variables including cognitive abnormalities and poor functioning might shed further light on the potential subtypes of illness most closely associated with genetic variation in YWHAH.
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PMID:Family-based association of YWHAH in psychotic bipolar disorder. 1916 Apr 47

Schizophrenia has a strong genetic basis, and genome-wide association studies (GWAS) have shown that effect sizes for individual genetic variants which increase disease risk are small, making detection and validation of true disease-associated risk variants extremely challenging. Specifically, we first identify genes with exons showing differential expression between cases and controls, indicating a splicing mechanism that may contribute to variation in disease risk and focus on those showing consistent differential expression between blood and brain tissue. We then perform a genome-wide screen for SNPs associated with both normalised exon intensity of these genes (so called splicing QTLs) as well as association with schizophrenia. We identified a number of significantly associated loci with a biologically plausible role in schizophrenia, including MCPH1, DLG3, ZC3H13, and BICD2, and additional loci that influence splicing of these genes, including YWHAH. Our approach of integrating genome-wide exon intensity with genome-wide polymorphism data has identified a number of plausible SZ associated loci.
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PMID:Combined analysis of exon splicing and genome wide polymorphism data predict schizophrenia risk loci. 2450 84

Handedness is an elusive human behavioral phenotypes and the genetic basis of it remains unclear until now. The aim of this study is to evaluate the genetic correlations between left-handedness and multiple mental disorders, and explored the genes detected by genetic correlations. In this study, linkage disequilibrium score regression (LDSC) analysis was conducted to evaluate the genetic correlations between left-handedness and multiple mental disorders. The significant genetic correlation was only observed between left-handedness and schizophrenia (SCZ). For the observed genetic correlation, transcriptome-wide association study (TWAS) was performed to identify the genes associated with left-handedness and SCZ, including brain RNA-seq (CBR) and brain RNA-seq splicing (CBRS). We detected several common genes associated with both left-handedness and SCZ, such as YWHAH, MAPT and ANO10. The common genes shared by left-handedness and SCZ were subjected to gene set enrichment analysis. Our study provides a novel clue for understanding the genetic correlation between left-handedness and SCZ.
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PMID:Evaluating the Genetic Correlations Between Left-Handedness and Mental Disorder Using Linkage Disequilibrium Score Regression and Transcriptome-Wide Association Study. 3210 Jan 39

The seven human 14-3-3 proteins are encoded by the YWHA-gene family. They are expressed in the brain where they play multiple roles including the modulation of synaptic plasticity and neuronal development. Previous studies have provided arguments for their involvement in schizophrenia, but their role during disease onset is unknown. We explored the peripheral-blood expression level of the seven YWHA genes in 92 young individuals at ultra-high risk for psychosis (UHR). During the study, 36 participants converted to psychosis (converters) while 56 did not (non-converters). YWHA genes expression was evaluated at baseline and after a mean follow-up of 10.3 months using multiplex quantitative PCR. Compared with non-converters, the converters had a significantly higher baseline expression levels for 5 YWHA family genes, and significantly different longitudinal changes in the expression of YWHAE, YWHAG, YWHAH, YWHAS and YWAHZ. A principal-component analysis also indicated that the YWHA expression was significantly different between converters and non-converters suggesting a dysregulation of the YWHA co-expression network. Although these results were obtained from peripheral blood which indirectly reflects brain chemistry, they indicate that this gene family may play a role in psychosis onset, opening the way to the identification of prognostic biomarkers or new drug targets.
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PMID:Dysregulation of peripheral expression of the YWHA genes during conversion to psychosis. 3255 55