ArticlePLoS genetics2015
Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 102 citations in OpenAlex.
- Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis.American journal of respiratory cell and molecular biology · 2017Trial
- Molecular mechanisms of EPAS1 in regulating pulmonary vascular remodeling in COPD: a review.Molecular biology reports · 2026Review
- EPAS1 is associated with human muscle fiber composition and endurance phenotypes.Physiological reports · 2026Article
- Epigenetic dysregulation of IRF9 drives excessive interferon signaling in COPD.EMBO molecular medicine · 2026Article
- Article
- Epigenomic study of the lower airway reveals COPD-associated methylation patterns and potential microbiota links.BMJ open respiratory research · 2025Article
- Challenges in mimicking hypoxia: insights into HIF-regulated MiRNA expression induced by DMOG and CoClCell communication and signaling : CCS · 2025Article
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- Airway MMP-12 and DNA methylation in COPD: an integrative approach.Respiratory research · 2025Article
- Lung Transcriptomics Link Emphysema to Barrier Dysfunction and Macrophage Subpopulations.American journal of respiratory and critical care medicine · 2025Article
- DNA Methylation-Mediated Downregulation ofInternational journal of chronic obstructive pulmonary disease · 2025Article
- Reduced FEVInternational journal of chronic obstructive pulmonary disease · 2025Article
- EPAS1, a hypoxia- and ferroptosis-related gene, promotes malignant behaviour of cervical cancer by ceRNA and super-enhancer.Journal of cellular and molecular medicine · 2024Article
- Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis.Biomedicines · 2023Article
- The role ofHeliyon · 2023Article
- Integrative genetic and genomic networks identify microRNA associated with COPD and ILD.Scientific reports · 2023Article
- Genome-wide methylomic regulation of multiscale gene networks in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- High-resolution transcriptomic and epigenetic profiling identifies novel regulators of COPD.The EMBO journal · 2023Article
- Endotyping COPD: hypoxia-inducible factor-2 as a molecular "switch" between the vascular and airway phenotypes?European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Updated perspective of EPAS1 and the role in pulmonary hypertension.Frontiers in cell and developmental biology · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection: integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD.2015 · Feronjy, Robert [corrected to Foronjy, Robert F]
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic, epigenetic, and environmental factors are known to contribute to COPD risk and disease progression. Therefore we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity. EPAS1 is distinct in comparison with other key regulators in terms of methylation profile and downstream target genes. Genes predicted to be regulated by EPAS1 were enriched for biological processes including signaling, cell communications, and system development. We confirmed that EPAS1 protein levels are lower in human COPD lung tissue compared to non-disease controls and that Epas1 gene expression is reduced in mice chronically exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted genes that significantly overlapped with EPAS1 downstream genes in lung tissue including hypoxia responsive genes, and genes associated with emphysema severity. Our first integrative analysis of genome-wide DNA methylation and gene expression profiles illustrates that not only does DNA methylation play a 'causal' role in the molecular pathophysiology of COPD, but it can be leveraged to directly identify novel key mediators of this pathophysiology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.