PTSD or resilient - Genetic and Epigenetic association studies in police officers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE99755 | GEO | 2018/01/24
REPOSITORIES: GEO
Similar Datasets
Project description:Epigenetic (N=15) were based on the Illumina Infinium HumanMethylation450 BeadChip. We searched for differentially methylated probes (DMPs) and regions (DMRs).
2018-03-19 | GSE107211 | GEO
Project description:The aim of the study is to identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients. DNA from baseline peripheral blood mononuclear cells was extracted from treatment naive RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy (deltaDAS28) over the first 3 months in 69 RA patients.
2021-02-07 | E-MTAB-10159 | biostudies-arrayexpress
Project description:Aim: We aimed to investigate the impact of H. pylori on the epigenome in normal gastric mucosa and whether these changes constitute cancer risk. Method: The Infinium HumanMethylation450 BeadChip Kit was used to assess methylation Results: We found 1924 differentially methylated positions (DMPs) and 438 differentially methylated regions (DMRs) associated with H. pylori infection, most of which were hypermethylated. Significant methylation alterations identified in the initial sample set were replicated in a second validation set. The H. pylori-associated DMP/Rs showed marked stability after H. pylori clearance. Furthermore, we found 152 DMRs associated with cancer risk, regardless of H. pylori status. A methylation score derived using three biomarkers was a strong predictor of GC, with an area under the curve of 0.765.
2017-08-30 | GSE99553 | GEO
Project description:We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma versus healthy controls. We identified 119 differentially methylated regions (DMRs) and 118 differentially methylated probes (DMPs) after adjustment for age, gender, race/ethnicity, batch effects, inflation, and multiple comparisons (false discovery rate-adjusted q<0.05). Genes differentially methylated include those with established roles in asthma and atopy, components of the extracellular matrix, genes related to immunity, cell adhesion, epigenetic regulation, and airway obstruction. Hypo- and hypermethylated genes were associated with increased and decreased gene expression respectively (P<2.8x10-6 for DMRs and P<7.8x10-10 for DMPs). Quantitative analysis of methylation-expression relationships in 53 differentially expressed genes demonstrated that 32 (60%) have significant (q<0.05) methylation-expression relationships within 5kb of the gene. 10 loci selected based on the relevance to asthma, magnitude of methylation change, and asthma specific methylation-expression relationships were validated in an independent cohort of children with asthma. case control design with nasal epithelial cells from 36 atopic asthmatic and 33 nonatopic nonasthmatic children from the inner city
2015-11-01 | E-GEOD-65204 | biostudies-arrayexpress
Project description:Background: Psoriasis is a T cell-mediated chronic autoimmune/inflammatory disease. While some patients experience disease limited to the skin (skin psoriasis), others develop joint involvement (psoriatic arthritis; PsA). In the absence of disease- and/or outcome-specific biomarkers, and as arthritis can precede skin manifestations, diagnostic and therapeutic delays are common and contribute to disease burden and damage accrual. Objective: Altered epigenetic marks, including DNA methylation, contribute to effector T cell phenotypes and altered cytokine expression in autoimmune/inflammatory diseases. This project aimed at the identification of disease-/outcome-specific DNA methylation signatures in CD8+ T cells from patients with psoriasis and PsA as compared to heathy controls. Method: Peripheral blood CD8+ T cells from 9 healthy controls, 10 psoriasis and 7 PsA patients were collected to analyze DNA methylation marks using Illumina Human Methylation EPIC BeadChips (>850,000 CpGs per sample). Bioinformatic analysis was performed using R (minfi, limma, ChAMP and DMRcate packages). Results: DNA methylation profiles in CD8+ T cells differentiate healthy controls from psoriasis patients (397 Differentially Methylated Positions (DMPs); 9 Differentially Methylated Regions (DMRs) when ≥CpGs per DMR were considered; 2 DMRs for ≥10 CpGs). Furthermore, patients with skin psoriasis can be discriminated from PsA patients (1861 DMPs, 20 DMRs (≥5 CpGs per region), 4 DMRs (≥10 CpGs per region)). Gene ontology (GO) analyses considering genes with ≥1 DMP in their promoter delivered methylation defects in skin psoriasis and PsA primarily affecting the BMP signaling pathway and endopeptidase regulator activity, respectively. GO analysis of genes associated with DMRs between skin psoriasis and PsA demonstrated an enrichment of GABAergic neuron and cortex neuron development pathways. Treatment with cytokine blockers associated with DNA methylation changes (2372 DMPs; 1907 DMPs within promoters, 7 DMRs (≥5CpG per regions)) affecting transforming growth factor beta receptor and transmembrane receptor protein serine/threonine kinase signaling pathways. Lastly, a methylation score including TNF and IL-17 pathway associated DMPs inverse correlates with skin disease activity scores (PASI). Conclusion: Patients with skin psoriasis exhibit DNA methylation patterns in CD8+ T cells that allow differentiation from PsA patients and healthy individuals, and reflect clinical activity of skin disease. Thus, DNA methylation profiling promises potential as diagnostic and prognostic tool to be used for molecular patient stratification towards individualized treatment. This project aimed at the identification of disease-/outcome-specific DNA methylation signatures in CD8+ T cells from patients with psoriasis and PsA as compared to heathy controls.
2021-09-22 | GSE184500 | GEO
Project description:Recent work has identified roles for environmental, genetic and epigenetic factors in AD risk. Motivated by suspected roles for epigenetic modifications in AD, we performed a genome-wide screen of DNA methylation using the Illumina Infinium HumanMethylation450 array platform on bulk tissue samples from the superior temporal gyrus (STG) of AD cases and non-demented controls. We paired a sliding window approach with linear models that account for age, gender, ethnicity, and estimated cellular proportions (neuronal vs. glial), to characterize AD-associated differentially methylated regions (DMRs). Whole DNA was extracted from STG tissue dissections collected from deceased individuals with and without Alzheimers Disease. DNA was bisulfite converted and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.
2015-12-18 | E-GEOD-76105 | biostudies-arrayexpress
Project description:There is increasing evidence that interindividual epigenetic variation is an etiological factor in common human diseases. Such epigenetic variation could be genetic or non-genetic in origin, and epigenome-wide association studies (EWASs) are underway for a wide variety of diseases/phenotypes. However, performing an EWAS is associated with a range of issues not typically encountered in genome-wide association studies (GWASs), such as the tissue to be analyzed. In many EWASs, it is not possible to analyze the target tissue in large numbers of live humans, and consequently surrogate tissues are employed, most commonly blood. But there is as yet no evidence demonstrating that blood is more informative than buccal cells, the other easily accessible tissue. To assess the potential of buccal cells for use in EWASs, we performed a comprehensive analysis of a buccal cell methylome using whole-genome bisulfite sequencing. Strikingly, a buccal vs. blood comparison reveals >6X as many hypomethylated regions in buccal. These tissue-specific differentially methylated regions (tDMRs) are strongly enriched for DNaseI hotspots. Almost 75% of these tDMRs are not captured by commonly used DNA methylome profiling platforms such as Reduced Representational Bisulfite Sequencing and the Illumina Infinium HumanMethylation450 BeadChip, and they also display distinct genomic properties. Buccal hypo-tDMRs show a statistically significant enrichment near SNPs associated to disease identified through GWASs. Finally, we find that, compared with blood, buccal hypo-tDMRs show significantly greater overlap with hypomethylated regions in other tissues. We propose that for non-blood based diseases/phenotypes, buccal will be a more informative tissue for EWASs. Bisulphite converted DNA from the 22 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2013-03-28 | E-GEOD-45529 | biostudies-arrayexpress
Project description:Background While smoking is known to associate with development of multiple diseases, the underlying mechanisms are still poorly understood. Tobacco smoking can modify the chemical integrity of DNA leading to changes in transcriptional activity, partly through an altered epigenetic state. We aimed to investigate the impact of smoking on lung cells collected from bronchoalveolar lavage (BAL). Methods We profiled changes in DNA methylation (5mC) and its oxidized form hydroxymethylation (5hmC) using conventional bisulfite (BS) treatment and oxidative bisulfite treatment with Illumina Infinium MethylationEPIC BeadChip, and examined gene expression by RNA-seq in healthy smokers. Findings We identified 1,667 BS methyl (5mC+5hmC), 1,756 5mC and 67 5hmC differentially methylated positions (DMPs) between smokers and nonsmokers (FDR <0.05, absolute Δβ >0.15). Both 5mC DMPs and to a lesser extent BS methyl (5mC+5hmC) were predominantly hypomethylated. In contrast, almost all 5hmC DMPs were hypermethylated, supporting the hypothesis that smoking-associated oxidative stress can lead to DNA demethylation, via the established sequential oxidation of which 5hmC is the first step. While we confirmed differential methylation of previously reported smoking-associated BS methyl CpGs using former generations of BeadChips in alveolar macrophages, the large majority of identified DMPs, BS methyl (1,639/1,667), 5mC (1,738/1,756), and 5hmC (67/67), have not been previously reported. Most of these novel smoking-associating sites are specific to the EPIC BeadChip and, interestingly, many of them are associated to FANTOM5 enhancers. Transcriptional changes affecting 633 transcripts were consistent with DNA methylation profiles and converged to alteration of genes involved in migration, signaling and inflammatory response of immune cells. Interpretation Collectively, these findings suggest that tobacco smoke exposure epigenetically modifies BAL cells, possibly involving a continuous active demethylation and subsequent increased activity of inflammatory processes in the lungs. -
2019-06-21 | GSE133062 | GEO
Project description:Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two genetic polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data highlight the cell type of origin of epigenetic signals seen in whole blood; IBD-associated hypermethylation within the TXK gene transcription start-sitepromoter region negatively correlates with gene expression in whole blood and CD8+ T-cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD are relatedrelate to underlying genotype and associate with cell-specific alteration in gene expression.
2016-11-13 | GSE87648 | GEO
Project description:Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two genetic polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data highlight the cell type of origin of epigenetic signals seen in whole blood; IBD-associated hypermethylation within the TXK gene transcription start-sitepromoter region negatively correlates with gene expression in whole blood and CD8+ T-cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD are relatedrelate to underlying genotype and associate with cell-specific alteration in gene expression.
2016-11-13 | GSE87640 | GEO