Genome-wide expression analysis of peripheral blood identifies candidate biomarkers for schizophrenia

Kuzman, Martina Rojnić; Medved, Vesna; Terzić, Janoš; Krainc, Dimitri

doi:10.1016/j.jpsychires.2009.03.005

Cited by 62 publications

(41 citation statements)

References 25 publications

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“…This approach has typically led to a large set of mRNAs or proteins being proposed as possible biomarkers in Sz but most findings await replication. Briefly, in a whole blood study from people during their first onset of Sz, the expression of glucose transporter (SLC2A3) and actin assembly factor (DAAM2) were increased, whereas zinc metallopeptidase, neurolysin 1 and myosin C were significantly decreased, compared to controls [129] , indicating peripheral mRNA of these genes could be a potential biomarkers in early stage of disease course. A genomewide expression analysis in PBMC samples from people with Sz was characterized by alterations of genes with immune system function [133,135] with some differentially expressed genes, such as argonaure 2, myocyte enhancer factor 2D, Enah/Vasp-like, peptidase inhibitor 3, S100 calcium binding protein A12 (S100A12), defensin α4 (DEFα4 [133] ) as well as AKT1 [135] being confirmed as changed using qPCR, the result supporting the hypothesis that the disorder has a significant immunological component in its etiology.…”

Section: The Human Transcriptome and Human Proteome Studiesmentioning

confidence: 99%

“…Of the studies discussed, only one followed up the differentially expressed RNA levels in whole blood of first onset Sz people for 1224 mo [129] . DAAM2, one of five differentially expressed genes, returned to control levels in the whole blood when people were in remission after their first psychotic episode, suggesting this mRNA could be altered by antipsychotics and may be a potential marker for treatment response.…”

Section: The Human Transcriptome and Human Proteome Studiesmentioning

confidence: 99%

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Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Lai

Scarr

Udawela

et al. 2016

WJP

140

108

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Identifying biomarkers that can be used as diagnostics or predictors of treatment response (theranostics) in people with schizophrenia (Sz) will be an important step towards being able to provide personalized treatment. Findings from the studies in brain tissue have not yet been translated into biomarkers that are practical in clinical use because brain biopsies are not acceptable and neuroimaging techniques are expensive and the results are inconclusive. Thus, in recent years, there has been search for blood-based biomarkers for Sz as a valid alternative. Although there are some encouraging preliminary data to support the notion of peripheral biomarkers for Sz, it must be acknowledged that Sz is a complex and heterogeneous disorder which needs to be further dissected into subtype using biological based and clinical markers. The scope of this review is to critically examine published blood-based biomarker of Sz, focusing on possible uses for diagnosis, treatment response, or their relationship with schizophreniaassociated phenotype. We sorted the studies into six categories which include: (1) brain-derived neurotrophic factor; (2) inflammation and immune function; (3) neurochemistry; (4) oxidative stress response and metabolism; (5) epigenetics and microRNA; and (6) transcriptome and proteome studies. This review also summarized the molecules which have been conclusively reported as potential blood-based biomarkers for Sz in different blood cell types. Finally, we further discusses the pitfall of current blood-based studies and suggest that a prediction model-based, Sz specific, blood World Journal of Psychiatry W J P oriented study design as well as standardize blood collection conditions would be useful for Sz biomarker development.

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Section: The Human Transcriptome and Human Proteome Studiesmentioning

confidence: 99%

Section: The Human Transcriptome and Human Proteome Studiesmentioning

confidence: 99%

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Lai

Scarr

Udawela

et al. 2016

WJP

140

108

View full text Add to dashboard Cite

show abstract

“…[16][17][18][19][20][21][22] Therefore, gene expression profiling in blood may provide additional insight into the etiology of the disease. We performed the gene expression analyses using whole-blood samples of a relatively large sample of schizophrenia patients and controls.…”

Section: Introductionmentioning

confidence: 99%

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

et al. 2012

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and The PGC Schizophrenia (GWAS) Consortium 7There is genetic evidence that schizophrenia is a polygenic disorder with a large number of loci of small effect on disease susceptibility. Genome-wide association studies (GWASs) of schizophrenia have had limited success, with the best finding at the MHC locus at chromosome 6p. A recent effort of the Psychiatric GWAS consortium (PGC) yielded five novel loci for schizophrenia. In this study, we aim to highlight additional schizophrenia susceptibility loci from the PGC study by combining the top association findings from the discovery stage (9394 schizophrenia cases and 12 462 controls) with expression QTLs (eQTLs) and differential gene expression in whole blood of schizophrenia patients and controls. We examined the 6192 singlenucleotide polymorphisms (SNPs) with significance threshold at Po0.001. eQTLs were calculated for these SNPs in a sample of healthy controls (n¼437). The transcripts significantly regulated by the top SNPs from the GWAS meta-analysis were subsequently tested for differential expression in an independent set of schizophrenia cases and controls (n¼202). After correction for multiple testing, the eQTL analysis yielded 40 significant cis-acting effects of the SNPs. Seven of these transcripts show differential expression between cases and controls. Of these, the effect of three genes (RNF5, TRIM26 and HLA-DRB3) coincided with the direction expected from meta-analysis findings and were all located within the MHC region. Our results identify new genes of interest and highlight again the involvement of the MHC region in schizophrenia susceptibility.

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“…But each also remains curiously under-represented in mainstream GxE research today. This is despite evidence to suggest they may serve a functional purpose as biomarkers of environmentally-induced pathogenesis, susceptibility, illness progression and treatment outcome [146][147][148][149][150][151][152] . Despite these documented examples, each discipline also faces thematic questions about how to achieve methodological best practice, given their various respective constraints 147,153,154 .…”

Section: Resultsmentioning

confidence: 99%

Old Obstacles on New Horizons: The Challenge of Implementing Gene X Environment Discoveries in Schizophrenia Research

Iyegbe

Modinos

Sanchez³

2012

Public Health - Methodology, Environmental and Systems Issues

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Genome-wide expression analysis of peripheral blood identifies candidate biomarkers for schizophrenia

Cited by 62 publications

References 25 publications

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

Old Obstacles on New Horizons: The Challenge of Implementing Gene X Environment Discoveries in Schizophrenia Research

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