COPD is Associated with Epigenome-wide Differential Methylation in BAL Lung Cells
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ABSTRACT:
PROVIDER: PRJNA817216 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on bronchoalveolar lavage (BAL) cells. Bronchoscopies were performed in 18 COPD subjects and 15 controls (ex- and current smokers). DNA methylation was measured with Illumina MethylationEPIC BeadChip covering >850,000 CpGs. Differentially methylated positions (DMPs) were examined for 1) enrichment in pathways and functional gene relationships using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology; 2) accelerated aging using Horvath’s epigenetic clock; 3) correlation with gene expression; and 4) colocalization with genetic variation. We found 1,155 Bonferroni significant (P < 6.74 × 10-8) DMPs associated with COPD, many with large effect sizes. Functional analysis identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. Strong correlation was found between DNA methylation and chronological age, but not between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL cells. Thirty-nine percent of DMPs were co-localized with COPD-associated SNPs. To the best of our knowledge, this is the first EWAS of COPD on BAL cells, and our analyses revealed many differential methylation sites. Integration with mRNA data showed a strong functional readout for relevant genes, identifying sites where DNA methylation might directly impact expression. Almost half of DMPs were co-located with SNPs identified in previous GWAS of COPD, suggesting joint genetic and epigenetic pathways related to disease.
2022-03-17 | GSE198870 | GEO
Project description:DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on BAL cells. Bronchoscopies were performed in 18 subjects with COPD and 15 control subjects (ex- and current smokers). DNA methylation was measured using the Illumina MethylationEPIC BeadChip Kit, covering more than 850,000 CpGs. Differentially methylated positions (DMPs) were examined for 1) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology, 2) accelerated aging using Horvath's epigenetic clock, 3) correlation with gene expression, and 4) colocalization with genetic variation. We found 1,155 Bonferroni-significant (P < 6.74 × 10-8) DMPs associated with COPD, many with large effect sizes. Functional analysis identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. Strong correlation was found between DNA methylation and chronological age but not between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL cells. Thirty-nine percent of DMPs were colocalized with COPD-associated SNPs. To the best of our knowledge, this is the first epigenome-wide association study of COPD on BAL cells, and our analyses revealed many differential methylation sites. Integration with mRNA data showed a strong functional readout for relevant genes, identifying sites where DNA methylation might directly affect expression. Almost half of DMPs were colocated with SNPs identified in previous genome-wide association studies of COPD, suggesting joint genetic and epigenetic pathways related to disease.
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Project description:Background: We got interested whether genes of airway basal cells are enriched in COPD. Methods: Bronchoscopy with bronchial brushes and bronchoalveolar lavage was performed in 28 patients with COPD and 29 healthy donors and isolated BAL cells.Transcriptome of BAL cells were studied by using Affymetrix Human Genome U133 Plus 2.0 array on an Affymetrix platform. Microarray data were normalized data were imported, log2-transformed and quantile normalized using robust multi-array average (RMA). We tested enrichment for airway basal cells by ROMER enrichment analysis. Results: we did not find enrichment of airway basal cell genes in COPD compared to healthy volunteers.
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Project description:Bronchoalveolar lavage samples collected from lung transplant recipients. Numeric portion of sample name is an arbitrary patient ID and AxBx number indicates the perivascular (A) and bronchiolar (B) scores from biopsies collected on the same day as the BAL fluid was collected. Several patients have more than one sample in this series and can be determined by patient number followed by a lower case letter. Acute rejection state is determined by the combined A and B score - specifically, a combined AB score of 2 or greater is considered an acute rejection. Keywords = Bronchoalveolar lavage Keywords = lung transplant Keywords: other
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Project description:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease typified by not fully reversible and often progressive airflow obstruction, along with persistent respiratory symptoms. This gap is due to lack of animal models that more closely mimic human COPD are needed to bridge translational gaps. Commonly used mice model produces primarily emphysematous disease and do not develop features pathognomonic for chronic bronchitis. Suggesting the potential for additional molecular insights to be obtained from animal models that exhibit COPD with features of chronic bronchitis and emphysema, as in humans. We sought to identify whether our ferret model of COPD captures unique genetic signatures in comparison to mouse models that can help improve understanding of the molecular pathogenesis of COPD and promote the development of new and effective therapies.
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