Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
DNA methylation in lung cells is associated with asthma endotypes and genetic risk
Jessie Nicodemus-Johnson, … , Yoav Gilad, Carole Ober
Jessie Nicodemus-Johnson, … , Yoav Gilad, Carole Ober
Published December 8, 2016
Citation Information: JCI Insight. 2016;1(20):e90151. https://doi.org/10.1172/jci.insight.90151.
View: Text | PDF
Research Article Genetics Pulmonology

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

  • Text
  • PDF
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.

Authors

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

×

Figure 1

Differential methylation in airway epithelial cells from asthmatic and control subjects.

Options: View larger image (or click on image) Download as PowerPoint
Differential methylation in airway epithelial cells from asthmatic and c...
(A) Volcano plot showing methylation differences between asthmatic (n = 74) and nonasthmatic (n = 41) individuals. Mean differences in β values are shown on the x axis. Dark gray indicates CpGs that differ between asthmatics and nonasthmatics at q ≤ 0.05; light gray indicates CpGs with a fold change of >5%; The black dots indicate non-significant sites at a q > 0.05. (B) Manhattan plot of 327,271 CpGs in our analysis of asthma-associated differentially methylated CpG sites. P values (y axis) correspond to the differences in methylation between asthmatic and control subjects. The red line corresponds to the q value threshold (FDR 5%). (C) Box plot showing methylation levels at a CpG site (cg11303839) upstream of the transcription start site of CCL26 (encoding eotaxin 3), a chemokine elevated in the airways of asthmatic subjects. Box plot displays the median, first and third quartiles, and 95% confidence intervals. (D) Scatter plot showing the correlation between CCL26 transcript abundance and cg11303839 methylation levels for 81 individuals with both gene expression and methylation data. In C and D, black points are nonasthmatics and red are asthmatics.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts