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Gene Expression in Peripheral Blood Leucocytes in Monozygotic Twins Discordant for Chronic Fatigue

ABSTRACT: Background. Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes. Methods. Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue. Biological sampling conditions were standardized and RNA stabilizing media were used. These methodological features provide rigorous control for bias resulting from case-control mismatched ancestry and experimental error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus 2.0 arrays. Findings. There were no significant differences in gene expression for any transcript. Conclusions. Contrary to our expectations, we were unable to identify a biomarker for chronic fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings in prior studies may have resulted from experimental bias.

ORGANISM(S): Homo sapiens

PROVIDER: GSE16059 | GEO | 2009/05/12

SECONDARY ACCESSION(S): PRJNA115475

REPOSITORIES: GEO

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Gene Expression in Peripheral Blood Leucocytes in Monozygotic Twins Discordant for Chronic Fatigue

Project description:Background. Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes. Methods. Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue. Biological sampling conditions were standardized and RNA stabilizing media were used. These methodological features provide rigorous control for bias resulting from case-control mismatched ancestry and experimental error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus 2.0 arrays. Findings. There were no significant differences in gene expression for any transcript. Conclusions. Contrary to our expectations, we were unable to identify a biomarker for chronic fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings in prior studies may have resulted from experimental bias. Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue.

2009-05-12 | E-GEOD-16059 | biostudies-arrayexpress

DNA Methylation Patterns Associated with Fatigue in Primary SjÃ¶grenâs Syndrome

Project description:Genome-wide analysis of DNA methylation profiles from patients with SjÃ¶gren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary SjÃ¶grenâs syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. Case-case study including SjÃ¶gren's patients with high fatigue (n=24) and patients with low fatigue levels (n=24)

2015-12-04 | E-GEOD-75679 | biostudies-arrayexpress

DNA Methylation Patterns Associated with Fatigue in Primary Sjögren’s Syndrome

Project description:Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögren’s syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array.

2015-12-04 | GSE75679 | GEO

A transcriptional signature of fatigue derived from patients with primary Sjögren's Syndrome

Project description:Fatigue is a debilitating condition with a significant impact on patients’ quality of life. Fatigue is frequently reported by patients suffering from primary Sjo ̈gren’s Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms.

2015-12-31 | GSE66795 | GEO

A transcriptional signature of fatigue derived from patients with primary SjÃ¶gren's Syndrome

Project description:Fatigue is a debilitating condition with a significant impact on patientsâ quality of life. Fatigue is frequently reported by patients suffering from primary Sjo Ìgrenâs Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. Whole blood samples from 131 fully-phenotyped pSS patients, stratified for the presence of fatigue, collected by the UK primary Sj Ìogrenâs Syndrome Registry were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). Contributor: The UK Primary SjÃ¶grenâs syndrome registry

2015-12-31 | E-GEOD-66795 | biostudies-arrayexpress

Sex-Dependent Transcriptional Changes in response to stress in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Project description:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing in 35 ME/CFS patients (24 female, 11 male) and 34 matched healthy control participants (21 female and 13 male) during and after an exercise challenge intended to provoke PEM. The effects of exertion in the male ME/CFS cohort highlighted pathways related to immune cell signaling (including IL-12) and NK cell cytotoxicity, while female ME/CFS patients did not have significant enough changes in gene expression to meet criteria for our study. Functional analysis during recovery from exercise showed that male ME/CFS patients had distinct changes in regulation of specific cytokine signals (including IL-1β). Female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses and NF-kβ signaling. The functional pathways and differentially expressed genes highlighted in this study provide insight into sex-specific predisposition and pathophysiology of ME/CFS.

2023-06-19 | GSE227375 | GEO

Gene expression analysis of cancer-related fatigue in whole blood from breast cancer survivors

2009-07-01 | GSE14786 | GEO

Gene expression analysis of cancer-related fatigue in whole blood from breast cancer survivors

Project description:Cancer-related fatigue is one of the most frequent complaints among breast cancer survivors, with a major negative impact on general life. However, the etiology behind this syndrome is still unraveled. Gene expression analysis was performed on whole blood samples from breast cancer survivors classified as either fatigued or non-fatigued at two consecutive time points. The analysis identified several gene sets concerning plasma and B cell pathways as different between the fatigue and non-fatigue groups, suggesting that a deregulation in these pathways might underlie the fatigue syndrome. The fatigue group also showed a higher mean level of leucocytes, lymphocytes and neutrophiles compared with the non-fatigue group, thus further implicating the immune system in the biology behind the fatigue syndrome. Keywords: Blood RNA and late side effects Breast cancer survivors treated with adjuvant radiotherapy at The Norwegian Radium Hospital between 1998 and 2002 were invited to participate in a study assessing late treatment effects in breast cancer survivors. In the present study, gene expression analysis was performed on whole blood samples from breast cancer survivors with and without persistent fatigue, to look for different expression patterns that might shed light on the biology behind cancer-related fatigue.

2009-07-01 | E-GEOD-14786 | biostudies-arrayexpress

Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Project description:Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

| PRJNA659027 | ENA

DNA methylation modifications associated with Chronic Fatigue Syndrome

Project description:Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Genomic DNA from 24 peripheral blood mononuclear cells (PBMC) samples (12 CFS, 12 controls) were bisulfite-converted and hybridised to the Illumina Infinium HumanMethylation450 BeadChip. GenomeStudio files were generated and the data was analyzed using the Illumina Methylation Analyzer R package.

2014-08-12 | E-GEOD-59489 | biostudies-arrayexpress

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