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Schizophrenia Bioinformatics

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https://www.readbyqxmd.com/read/28125460/varscan2-analysis-of-de-novo-variants-in-monozygotic-twins-discordant-for-schizophrenia
#1
Emma Reble, Christina A Castellani, Melkaye G Melka, Richard O'Reilly, Shiva M Singh
OBJECTIVES: Monozygotic twins with near-identical genotypes and discordance for complex diseases represent an exceptional resource to ascertain disease etiology. This strategy has been particularly effective with the availability of high-resolution complete individual genome sequencing. The challenge is using effective approaches to identify relevant differences that may cause or contribute toward disease discordance. PARTICIPANTS AND METHODS: This study carried out a VarScan2 bioinformatic analysis and a pathway analysis on whole-genome sequences from two sets of monozygotic twins...
April 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/28072411/the-early-growth-response-protein-1-mir-30a-5p-neurogenic-differentiation-factor-1-axis-as-a-novel-biomarker-for-schizophrenia-diagnosis-and-treatment-monitoring
#2
S Liu, F Zhang, Y Y Shugart, L Yang, X Li, Z Liu, N Sun, C Yang, X Guo, J Shi, L Wang, L Cheng, K Zhang, T Yang, Y Xu
To date, diagnosis of schizophrenia is still based on clinical interviews and careful observations, which is subjective and variable, and can lead to misdiagnosis and/or delay in diagnosis. As early intervention in schizophrenia is important in improving outcomes, objective tests that can be used for schizophrenia diagnosis or treatment monitoring are thus in great need. MicroRNAs (miRNAs) negatively regulate target gene expression and their biogenesis is tightly controlled by various factors including transcription factors (TFs)...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28065900/exploring-the-predictive-power-of-polygenic-scores-derived-from-genome-wide-association-studies-a-study-of-10-complex-traits
#3
Hon-Cheong So, Pak C Sham
MOTIVATION: It is hoped that advances in our knowledge in disease genomics will contribute to personalized medicine such as individualized preventive strategies or early diagnoses of diseases. With the growth of genome-wide association studies (GWAS) in the past decade, how far have we reached this goal? In this study we explored the predictive ability of polygenic risk scores (PRSs) derived from GWAS for a range of complex disease and traits. RESULTS: We first proposed a new approach to evaluate predictive performances of PRS at arbitrary P-value thresholds...
January 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/27992301/fine-mapping-of-antipsychotic-response-genome-wide-association-studies-reveals-novel-regulatory-mechanisms
#4
Ellen S Ovenden, Britt I Drögemöller, Lize van der Merwe, Bonginkosi Chiliza, Laila Asmal, Robin A Emsley, Louise Warnich
AIM: Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response. MATERIALS & METHODS: Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103)...
January 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/27913161/novel-brain-expressed-rna-identified-at-the-mir137-schizophrenia-associated-locus
#5
Olympia Gianfrancesco, Alix Warburton, David A Collier, Vivien J Bubb, John P Quinn
Genome-wide association studies (GWAS) have identified a locus on chromosome 1p21.3 to be highly associated with schizophrenia. A microRNA, MIR137, within this locus has been proposed as the gene causally associated with schizophrenia, due to its known role as a regulator of neuronal development and function. However, the involvement of other genes within this region, including DPYD (dihydropyrimidine dehydrogenase), is also plausible. In this communication, we describe a previously uncharacterised, brain-expressed RNA, EU358092, within the schizophrenia-associated region at 1p21...
November 29, 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27898073/proteomic-analysis-of-the-postsynaptic-density-implicates-synaptic-function-and-energy-pathways-in-bipolar-disorder
#6
M Föcking, P Dicker, L M Lopez, M Hryniewiecka, K Wynne, J A English, G Cagney, D R Cotter
The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27852062/disrupted-in-schizophrenia-1-disc1-inhibits-glioblastoma-development-by-regulating-mitochondria-dynamics
#7
Xingchun Gao, Yajing Mi, Na Guo, Zhifang Hu, Fengrui Hu, Dou Liu, Lei Gao, Xingchun Gou, Weilin Jin
Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentalized protein, in mitochondria. But whether DISC1 could regulate GBM tumorigenesis via mitochondria is still unknown. We determined the expression level of DISC1 by both bioinformatics analysis and tissue analysis, and found that DISC1 was highly expressed in GBM...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826551/noncoding-rna-regulation-of-dopamine-signaling-in-diseases-of-the-central-nervous-system
#8
REVIEW
William T Carrick, Brandi Burks, Murray J Cairns, Jannet Kocerha
Dopaminergic neurotransmission mediates a majority of the vital central nervous system functions. Disruption of these synaptic events provokes a multitude of neurological pathologies, including Parkinson's, schizophrenia, depression, and addiction. Growing evidence supports a key role for noncoding RNA (ncRNA) regulation in the synapse. This review will discuss the role of both short and long ncRNAs in dopamine signaling, including bioinformatic examination of the pathways they target. Specifically, we focus on the contribution of ncRNAs to dopaminergic dysfunction in neurodegenerative as well as psychiatric disease...
2016: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/27754286/br-07-1-development-of-the-cell-microarray-for-high-throughput-analysis-of-gut-microbiota
#9
Seong-Tshool Hong
The human intestine contains a massive and complex microbial community called gut microbiota. A typical human carries 100 trillion microbes in his/her body which is 10 times greater than the number of their host cells, i.e. whole number of human cells. A combined microbial genome constituting gut microbiota is well excess our own human genome. The microbial composition of gut microbiotata and its role on diseases became a booming area of research, presenting a new paradigm of opportunities for modern medicines...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643284/br-07-1-development-of-the-cell-microarray-for-high-throughput-analysis-of-gut-microbiota
#10
Seong-Tshool Hong
The human intestine contains a massive and complex microbial community called gut microbiota. A typical human carries 100 trillion microbes in his/her body which is 10 times greater than the number of their host cells, i.e. whole number of human cells. A combined microbial genome constituting gut microbiota is well excess our own human genome. The microbial composition of gut microbiotata and its role on diseases became a booming area of research, presenting a new paradigm of opportunities for modern medicines...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27525637/identification-and-potential-regulatory-properties-of-evolutionary-conserved-regions-ecrs-at-the-schizophrenia-associated-mir137-locus
#11
Olympia Gianfrancesco, Daniel Griffiths, Paul Myers, David A Collier, Vivien J Bubb, John P Quinn
Genome-wide association studies (GWAS) have identified a region at chromosome 1p21.3, containing the microRNA MIR137, to be among the most significant associations for schizophrenia. However, the mechanism by which genetic variation at this locus increases risk of schizophrenia is unknown. Identifying key regulatory regions around MIR137 is crucial to understanding the potential role of this gene in the aetiology of psychiatric disorders. Through alignment of vertebrate genomes, we identified seven non-coding regions at the MIR137 locus with conservation comparable to exons (>70 %)...
October 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27512062/nf-%C3%AE%C2%BAb-and-irf1-induce-endogenous-retrovirus-k-expression-via-interferon-stimulated-response-elements-in-its-5-long-terminal-repeat
#12
Mamneet Manghera, Jennifer Ferguson-Parry, Rongtuan Lin, Renée N Douville
UNLABELLED: Thousands of endogenous retroviruses (ERV), viral fossils of ancient germ line infections, reside within the human genome. Evidence of ERV activity has been observed widely in both health and disease. While this is most often cited as a bystander effect of cell culture or disease states, it is unclear which signals control ERV transcription. Bioinformatic analysis suggests that the viral promoter of endogenous retrovirus K (ERVK) is responsive to inflammatory transcription factors...
October 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27497442/a-novel-copy-number-variants-kernel-association-test-with-application-to-autism-spectrum-disorders-studies
#13
Xiang Zhan, Santhosh Girirajan, Ni Zhao, Michael C Wu, Debashis Ghosh
MOTIVATION: Copy number variants (CNVs) have been implicated in a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability and schizophrenia. Recent advances in high-throughput genomic technologies have enabled rapid discovery of many genetic variants including CNVs. As a result, there is increasing interest in studying the role of CNVs in the etiology of many complex diseases. Despite the availability of an unprecedented wealth of CNV data, methods for testing association between CNVs and disease-related traits are still under-developed due to the low prevalence and complicated multi-scale features of CNVs...
December 1, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27462272/activation-of-sterol-regulatory-element-binding-factors-by-fenofibrate-and-gemfibrozil-stimulates-myelination-in-zebrafish
#14
Yoshifumi Ashikawa, Yuhei Nishimura, Shiko Okabe, Shota Sasagawa, Soichiro Murakami, Mizuki Yuge, Koki Kawaguchi, Reiko Kawase, Toshio Tanaka
Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS), and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27401531/two-stage-replication-of-previous-genome-wide-association-studies-of-as3mt-cnnm2-nt5c2-gene-cluster-region-in-a-large-schizophrenia-case-control-sample-from-han-chinese-population
#15
Fanglin Guan, Tianxiao Zhang, Lu Li, Dongke Fu, Huali Lin, Gang Chen, Teng Chen
Schizophrenia is a devastating psychiatric condition with high heritability. Replicating the specific genetic variants that increase susceptibility to schizophrenia in different populations is critical to better understand schizophrenia. CNNM2 and NT5C2 are genes recently identified as susceptibility genes for schizophrenia in Europeans, but the exact mechanism by which these genes confer risk for schizophrenia remains unknown. In this study, we examined the potential for genetic susceptibility to schizophrenia of a three-gene cluster region, AS3MT-CNNM2-NT5C2...
October 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27187203/a-simple-yet-accurate-correction-for-winner-s-curse-can-predict-signals-discovered-in-much-larger-genome-scans
#16
T Bernard Bigdeli, Donghyung Lee, Bradley Todd Webb, Brien P Riley, Vladimir I Vladimirov, Ayman H Fanous, Kenneth S Kendler, Silviu-Alin Bacanu
MOTIVATION: For genetic studies, statistically significant variants explain far less trait variance than 'sub-threshold' association signals. To dimension follow-up studies, researchers need to accurately estimate 'true' effect sizes at each SNP, e.g. the true mean of odds ratios (ORs)/regression coefficients (RRs) or Z-score noncentralities. Naïve estimates of effect sizes incur winner's curse biases, which are reduced only by laborious winner's curse adjustments (WCAs). Given that Z-scores estimates can be theoretically translated on other scales, we propose a simple method to compute WCA for Z-scores, i...
September 1, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27184105/the-role-of-protein-intrinsic-disorder-in-major-psychiatric-disorders
#17
Luciana Tovo-Rodrigues, Mariana Recamonde-Mendoza, Vanessa Rodrigues Paixão-Côrtes, Estela M Bruxel, Jaqueline B Schuch, Deise C Friedrich, Luis A Rohde, Mara H Hutz
Although new candidate genes for Autism Spectrum Disorder (ASD), Schizophrenia (SCZ), Attention-Deficit/Hyperactivity Disorder (ADHD), and Bipolar Disorder (BD) emerged from genome-wide association studies (GWAS), their underlying molecular mechanisms remain poorly understood. Evidences of the involvement of intrinsically disordered proteins in diseases have grown in the last decade. These proteins lack tridimensional structure under physiological conditions and are involved in important cellular functions such as signaling, recognition and regulation...
September 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27163207/genetic-deletion-of-fibroblast-growth-factor-14-recapitulates-phenotypic-alterations-underlying-cognitive-impairment-associated-with-schizophrenia
#18
T K Alshammari, M A Alshammari, M N Nenov, E Hoxha, M Cambiaghi, A Marcinno, T F James, P Singh, D Labate, J Li, H Y Meltzer, B Sacchetti, F Tempia, F Laezza
Cognitive processing is highly dependent on the functional integrity of gamma-amino-butyric acid (GABA) interneurons in the brain. These cells regulate excitability and synaptic plasticity of principal neurons balancing the excitatory/inhibitory tone of cortical networks. Reduced function of parvalbumin (PV) interneurons and disruption of GABAergic synapses in the cortical circuitry result in desynchronized network activity associated with cognitive impairment across many psychiatric disorders, including schizophrenia...
May 10, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27153687/eps-an-empirical-bayes-approach-to-integrating-pleiotropy-and-tissue-specific-information-for-prioritizing-risk-genes
#19
Jin Liu, Xiang Wan, Shuangge Ma, Can Yang
MOTIVATION: Researchers worldwide have generated a huge volume of genomic data, including thousands of genome-wide association studies (GWAS) and massive amounts of gene expression data from different tissues. How to perform a joint analysis of these data to gain new biological insights has become a critical step in understanding the etiology of complex diseases. Due to the polygenic architecture of complex diseases, the identification of risk genes remains challenging. Motivated by the shared risk genes found in complex diseases and tissue-specific gene expression patterns, we propose as an Empirical Bayes approach to integrating Pleiotropy and Tissue-Specific information (EPS) for prioritizing risk genes...
June 15, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27120077/exome-sequencing-of-familial-bipolar-disorder
#20
Fernando S Goes, Mehdi Pirooznia, Jennifer S Parla, Melissa Kramer, Elena Ghiban, Senem Mavruk, Yun-Ching Chen, Eric T Monson, Virginia L Willour, Rachel Karchin, Matthew Flickinger, Adam E Locke, Shawn E Levy, Laura J Scott, Michael Boehnke, Eli Stahl, Jennifer L Moran, Christina M Hultman, Mikael Landén, Shaun M Purcell, Pamela Sklar, Peter P Zandi, W Richard McCombie, James B Potash
IMPORTANCE: Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare variant discovery has only recently become feasible with next-generation sequencing. OBJECTIVE: To utilize a combined family-based and case-control approach to exome sequencing in BD using multiplex families as an initial discovery strategy, followed by association testing in a large case-control meta-analysis...
June 1, 2016: JAMA Psychiatry
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