DNA methylation in lung cells is associated with asthma endotypes and genetic risk
Open accessAbstract
The epigenome provides a substrate through which environmental exposures can exert their effects on gene expression and disease risk, but the relative importance of epigenetic variation on human disease onset and progression is poorly characterized. Asthma is a heterogeneous disease of the airways, for which both onset and clinical course result from interactions between host genotype and environmental exposures, yet little is known about the molecular mechanisms for these interactions. We assessed genome-wide DNA methylation using the Infinium Human Methylation 450K Bead Chip and characterized the transcriptome by RNA sequencing in primary airway epithelial cells from 74 asthmatic and 41 nonasthmatic adults. Asthma status was based on doctor’s diagnosis and current medication use. Genotyping was performed using various Illumina platforms. Our study revealed a regulatory locus on chromosome 17q12-21 associated with asthma risk and epigenetic signatures of specific asthma endotypes and molecular networks. Overall, these data support a central role for DNA methylation in lung cells, which promotes distinct molecular pathways of asthma pathogenesis and modulates the effects of genetic variation on disease risk and clinical heterogeneity.
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Lung cell type specific priors were obtained from a DE study of freshly isolated airway epithelial cells of asthma patients and healthy controls55.
“Lung cell type specific priors were obtained from a DE study of freshly isolated airway epithelial cells of asthma patients and healthy controls55.”
From scPower accelerates and optimizes the design of multi-sample single cell transcriptomic studies (2021) · cites this paper as [55]
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- Authors
- Nicodemus-Johnson, J., Myers, R. A., Sakabe, N. J., Sobreira, D. R., Hogarth, D. K., Naureckas, E. T., Sperling, A. I., Solway, J., White, S. R., Nobrega, M. A., Nicolae, D. L., Gilad, Y., & Ober, C.
- Affiliations
- Department of Human Genetics,
- Department of Medicine, and
- University of Chicago (US)
- Corresponding author
- Ober, Carole
- ORCID
- Venue
- JCI Insight
- Published
- 2016-12-08
- Volume
- 1
- Issue
- 20
- Pages
- e90151-e90151
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5139904
- OpenAlex
- W2560541504
- Cited by
- 180
- References
- 55
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 23 · 2023: 13 · 2022: 18 · 2021: 29 · 2020: 28 · 2019: 23 · 2018: 18 · 2017: 2
- FWCI
- 11.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- AstraZeneca
- University of Chicago
- Cytokinetics
- National Institutes of Health (U01 AI106683)
- National Heart, Lung, and Blood Institute (P01HL070831, T32HL007605)
- National Institute of Allergy and Infectious Diseases (AI106683, U19AI095230, P01AI106683, AI-095230)
- Office of Research on Women's Health
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- asthma, DNA methylation, asthma endotypes, airway epithelial cells, epigenetics, genetic risk, host-environment interactions, asthma pathogenesis, transcriptome, lung cells
- MeSH terms
- Adult, Asthma, Epithelial Cells, Female, Humans, Lung, Male, Middle Aged, Gene Expression, Case-Control Studies, DNA Methylation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Epigenesis, Genetic, Transcriptome
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