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The full text of this article hosted at iucr. Use the link below to share a full-text version of this article with your friends and colleagues. Learn more. Glutamate receptors play key roles in learning and memory. Hence, abnormalities in glutamate receptors within the frontal cortex may be associated with schizophrenia.

In addition, emerging evidence indicates that glutamate receptors may be involved in the actions of antipsychotic drugs. Volume 71 , Issue 6. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account. If the address matches an existing account you will receive an email with instructions to retrieve your username.

Journal of Neurochemistry Volume 71, Issue 6. Free Access. Boris P. Address correspondence and reprint requests to Dr. Tools Request permission Export citation Add to favorites Track citation.

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Share Give access Share full text access. Share full text access. MICB was found differentially expressed between schizophrenia cases and controls. Hakobyan et al. We prioritized 10 target genes for schizophrenia. They were all differentially expressed between schizophrenia cases and controls, validated in mouse models and MalaCards directly.

There were 12 approved drugs from biotech targeted to functional genes, while Pegademase bovine is used for the treatment of adenosine deaminase, which is involved in the pathophysiology of schizophrenia Botulinum Toxin Type B is used for dystonia, which is one of the symptoms of schizophrenia. The other 10 drugs were all non-psychiatric medications. We searched for the potential clinical relevance of those non-psychiatric medications in context of schizophrenia. Patients with schizophrenia have excess cardiovascular morbidity and mortality There was high prevalence of psychopathology in children with blood disorders It was found that autoimmune diseases were associated with an increased risk of developing schizophrenia An important role of peripheral immune-to-brain communication pathways was suggested in schizophrenia, and there was an association between elevated levels of circulating inflammatory cytokines and subsequent risk of psychosis Patients with schizophrenia have been found with a reduced risk of cancer It has been found that patients with schizophrenia have a hyper-opaminergic system and dopamine has the ability to inhibit tumor angiogenesis Consequently, these non-psychiatric medications may have chance to be applied to schizophrenia, as well to a better understanding of the schizophrenia pathogenesis.

There are still some limitations of this study. Because of the limitation of current available pQTL data, only blood tissue was used in this study. Thus, we may miss many pQTL target genes. Therefore, more pQTL target genes may be obtained if more large-scale data from schizophrenia relevant tissues are available. In addition, we mainly focused on protein-coding genes.

Other target genes which encode non-coding RNAs may also play roles in the pathogenesis of schizophrenia. Besides, we did meta-analyses across distinct tissue types firstly because blood was used as a surrogate for brain tissues in schizophrenia studies 56 , 57 , We aimed to find the genes expressed consistently in these schizophrenia-related tissues. Secondly, meta-analysis applied to different tissues to identify non-tissue specific genes was commonly used 13 , This did have some limitations since different tissues have different gene expression patterns, which may introduce heterogeneity.

In conclusion, we acquired SNPs associated with schizophrenia and provided a comprehensive annotation for all susceptibility loci. Finally, we acquired target protein-coding genes. One hundred and sixty-eight of these genes Besides, Our results may offer holistic guides for post-GWAS functional experiments. Saha, S. A systematic review of mortality in schizophrenia—is the differential mortality gap worsening over time? Psychiatry 64 , — Sullivan, P. Schizophrenia as a complex trait—evidence from a meta-analysis of twin studies.

Molecular Neuropharmacology of LSD

Psychiatry 60 , — Brennand, K. Modelling schizophrenia using human induced pluripotent stem cells. Nature , — Maurano, M. Systematic localization of common disease-associated variation in regulatory DNA. Science , — Dunham, I. An integrated encyclopedia of DNA elements in the human genome. Nature , 57—74 Kundaje, A. Integrative analysis of reference human epigenomes.

Wang, G. Gene variants in noncoding regions and their possible consequences. Pharmacogenomics 7 , — Hazelett, D. Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS Genet. Yao, L. Functional annotation of colon cancer risk SNPs. Coetzee, S.

Welter, D. Nucleic Acids Res. McClellan, J.

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Genetic heterogeneity in human disease. Cell , — Ripke, S. Biological insights from schizophrenia-associated genetic loci. Pardinas, A. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Wang, K. Choi, Y. Bioinformatics 31 , — Kumar, P. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.

Adzhubei, I. A method and server for predicting damaging missense mutations. Methods 7 , — Kircher, M. A general framework for estimating the relative pathogenicity of human genetic variants. Liu, C. BMC Genomics 13 , Kumar, S.

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Chiocchetti, A. Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders. Psychiatry 6 , e Cowper-Sal-lari, R. Jaffe, A. Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex.

Fromer, M. Gene expression elucidates functional impact of polygenic risk for schizophrenia. Bonder, M. Disease variants alter transcription factor levels and methylation of their binding sites. Zhu, Z. Lonsdale, J. Suhre, K. Connecting genetic risk to disease end points through the human blood plasma proteome. Willer, C. METAL: fast and efficient meta-analysis of genomewide association scans.

Bioinformatics 26 , — Lanz, T. STEP levels are unchanged in pre-frontal cortex and associative striatum in post-mortem human brain samples from subjects with schizophrenia, bipolar disorder and major depressive disorder. Arion, D. Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder. Psychiatry 20 , — A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.

Blake, J. Dickinson, M.

US8748621B2 - 1,3-disubstituted 4-(aryl-X-phenyl)-1H-pyridin-2-ones - Google Patents

High-throughput discovery of novel developmental phenotypes. Boyle, E. An expanded view of complex traits: from polygenic to omnigenic. Sekar, A. Schizophrenia risk from complex variation of complement component 4. Carter, C. Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii.

Shirts, B. Polymorphisms in MICB are associated with human herpes virus seropositivity and schizophrenia risk. Hakobyan, S. Classical pathway complement activity in schizophrenia. Zhang, S. Role of CACNA1C gene polymorphisms and protein expressions in the pathogenesis of schizophrenia: a case-control study in a Chinese population. Genome-wide association study identifies five new schizophrenia loci.

Javitt, D. Recent advances in the phencyclidine model of schizophrenia. Psychiatry , — Hoseth, E. A study of TNF pathway activation in schizophrenia and bipolar disorder in plasma and brain tissue. Labrie, V.

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