Cited by 200Asthma and respiratory diseasesEpigenetics and DNA MethylationGenetic Associations and Epidemiology

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

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Nicodemus-Johnson, Jessie, Myers, Rachel A., Sakabe, Noburu J., Sobreira, Debora R., Hogarth, Douglas K., Naureckas, Edward T., Sperling, Anne I., Solway, Julian, White, Steven R., Nobrega, Marcelo A., Nicolae, Dan L., Gilad, Yoav, Ober, Carole·2016·JCI Insight

DOI 10.1172/jci.insight.90151PMC PMC5139904

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Abstract

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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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: Myers, Rachel A.
Hogarth, Douglas K.
Naureckas, Edward T.
Sperling, Anne I.
Solway, Julian
White, Steven R.
Nicolae, Dan L.
Gilad, Yoav
Ober, Carole
Venue: JCI Insight
Publisher: American Society for Clinical Investigation
Published: 2016-12-08
Volume: 1
Issue: 20
Pages: e90151-e90151
ISSN: 2379-3708 (ISSN-L)
DOI: 10.1172/jci.insight.90151
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 › Pulmonary and Respiratory Medicine › 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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DNA methylation in lung cells is associated with asthma endotypes and genetic risk

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