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DNA methylation in lung cells is a key modulator of asthma endotypes and genetic risk [DNA methylation]

ABSTRACT: We generated genome-wide methylation data using the 450K from freshly isolated airway epithelial cells of asthmatics and non-asthmatics. This data was paired with genome-wide genetic and gene expression data from the same individuals allowing for an integrated analysis of genetic, transcriptional, and epigenetic signatures in asthma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE85566 | GEO | 2017/01/06

SECONDARY ACCESSION(S): PRJNA338807

REPOSITORIES: GEO

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DNA methylation in lung cells is a key modulator of asthma endotypes and genetic risk [RNA-seq]

Project description:We generated genome-wide RNASeq data from freshly isolated airway epithelial cells of asthmatics and non-asthmatics. This data was paired with genome-wide genetic and methylation data from the same individuals allowing for an integrated analysis of genetic, transcriptional, and epigenetic signatures in asthma.

2017-01-06 | GSE85567 | GEO

DNA methylation in lung cells is a key modulator of asthma endotypes and genetic risk

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-01-06 | GSE85568 | GEO

DNA methylation in lung cells is associated with asthma endotypes and genetic risk.

Project description: Not available

| S-EPMC5139904 | biostudies-literature

DNA methylation in lung cells is a key modulator of asthma endotypes and genetic risk

Project description:DNA methylation in lung cells is a key modulator of asthma endotypes and genetic risk

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DNA Methylation Changes and Childhood Asthma in the Inner City [methylation]

Project description:Background: Epigenetic marks, like asthma, are heritable. They are influenced by the environment, direct the maturation of T cellslymphocytes, and have been shown to enhance the development of allergic airways disease in mice. Thus, we hypothesized that epigenetic marks are associated with allergic asthma in inner-city children. Methods: We compared methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy controls, using DNA and RNA from peripheral blood mononuclear cells (PBMCs) from inner city children aged 6-12 years with persistent atopic asthma children and healthy controls. Results were externally validated with the GABRIELA study population. Results: Comparing asthmatics (N=97) to controls (N=97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthmatics, including IL-13, RUNX3, and a number of specific genes relevant to natural killer cells (KIR2DL4, KIR2DL3, KIR3DL1, and KLRD1) and T cells lymphocytes (TIGIT). 14 differentially methylated regions (DMRs) were associated with the serum IgE concentration of IgE, including RUNX3. These results were internally and externally validated with a global methylation assessment using a different methodology in our inner-city cohort and an independent European cohort (GABRIELA). Hypo- and hypermethylated genes tended to be associated with increased and decreased gene expression, respectively (P<0.6x10-11 for asthma and ; P<0.01 for IgE). To further explore the relationship between methylation and gene expression, we created a matrix of genomic changes in methylation versus transcriptional changes (methyl eQTL) for asthma, and identified cis- and trans-regulated genes whose expression was related to asthma asthma-associated methylation marks. peripheral blood mononuclear cells (PBMCs) from 97 atopic asthmatic and 97 nonatopic nonasthmatic children

2015-02-02 | E-GEOD-40576 | biostudies-arrayexpress

Nasal DNA methylation differentiates corticosteroid treatment response in pediatric asthma: A pilot study

Project description:Genome-wide DNA methylation profiling of nasal DNA from asthmatics hospitlaized for exacerbation. Samples were taken before steroid treatment and 18-24hr after steroid treatment. The Illumina Infinium HumanMethylation450 beadchips were used to generate DNA methylation profiles.

2017-10-23 | GSE104087 | GEO

Lung function, airway and peripheral basophils and eosinophils are associated with molecular pharmacogenomic endotypes of steroid response in severe asthma.

Project description:Sputum airway cells transcriptome from 19 asthmatics from the Severe Asthma Research Program at baseline and 6-8 weeks follow-up after a 40mg dose of intramuscular corticosteroid triamcinolone acetonide.

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DNA Methylation Changes and Childhood Asthma in the Inner City [methylation]

2015-02-02 | GSE40576 | GEO

Human rhinovirus infection causes different DNA methylation changes in nasal epithelial cells from healthy and asthmatic subjects

Project description:Background: Mechanisms underlying the development of virus-induced asthma exacerbations remain unclear. Objective: To investigate if epigenetic mechanisms could be involved in virus-induced asthma exacerbations, we undertook DNA methylation profiling in asthmatic and healthy nasal epithelial cells (NECs) during Human Rhinovirus (HRV) infection in vitro. Methods: Global and loci-specific methylation profiles were determined via Alu element and Infinium Human Methylation 450K microarray respectively. Principal components analysis identified the genomic loci influenced the most by disease-status and infection. Real-time PCR and pyrosequencing was used to confirm gene expression and DNA methylation respectively. Results: Global methylation was increased in Asthmatics during infection. Disease status and virus infection influenced the methylation of 389 loci. Healthy and asthmatic NECs were characterized predominately by methylation profiles and patterns in loci that were not influenced by virus infection. However, both groups also exhibited distinct DNA methylation profiles in response to infection. Despite these differences, we found that the methylation of small nucleolar RNA, H/ACA box 12 (SNORA12) was common during infection. Further analysis indicated a relationship existed between SNORA12 DNA methylation and gene expression in response to infection. Conclusions: Findings from our study indicate that in addition to the well described phenotypic and genomic differences, the airway epithelium of asthmatics is characterized by a distinct methylome and that epigenetic mechanism may contribute to the development of virus-induced asthma exacerbations. Bisulphite converted DNA from matched mock and human rhinovirus-16 infected nasal epithelial cells from Healthy (n=3) and Asthmatics (n=6) adults were hybridized to the Illumina DNA methylation 450K Bead Array.

2014-07-28 | E-GEOD-52074 | biostudies-arrayexpress

DNA Methylation Changes and Childhood Asthma in the Inner City [gene expression]

2015-02-02 | E-GEOD-40732 | biostudies-arrayexpress

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