The nasal methylome and childhood atopic asthma

Ivana V. Yang, Brent S. Pedersen, Andrew H. Liu, George T. O'Connor, Dinesh Pillai, Meyer Kattan, Rana Tawil Misiak, Rebecca Gruchalla, Stanley J. Szefler, Gurjit K. Khurana Hershey, Carolyn Kercsmar, Adam Richards, Allen D. Stevens, Christena A. Kolakowski, Melanie Makhija, Christine A. Sorkness, Rebecca Z. Krouse, Cynthia Visness, Elizabeth J. Davidson, Corinne E. Hennessy & 4 others Richard J. Martin, Alkis Togias, William W. Busse, David A. Schwartz

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma. Objective: We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma. Methods: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) versus healthy control subjects (n = 36). Results were validated in an independent population of asthmatic children (n = 30) by using a shared healthy control population (n = 36) and in an independent population of white adult atopic asthmatic patients (n = 12) and control subjects (n = 12). Results: We identified 186 genes with significant methylation changes, differentially methylated regions or differentially methylated probes, after adjustment for age, sex, race/ethnicity, batch effects, inflation, and multiple comparisons. Genes differentially methylated included those with established roles in asthma and atopy and genes related to extracellular matrix, immunity, cell adhesion, epigenetic regulation, and airflow obstruction. The methylation changes were substantial (median, 9.5%; range, 2.6% to 29.5%). Hypomethylated and hypermethylated genes were associated with increased and decreased gene expression, respectively (P < 2.8 × 10-6 for differentially methylated regions and P < 7.8 × 10-10 for differentially methylated probes). Quantitative analysis in 53 differentially expressed genes demonstrated that 32 (60%) have significant methylation-expression relationships within 5 kb of the gene. Ten loci selected based on the relevance to asthma, magnitude of methylation change, and methylation-expression relationships were validated in an independent cohort of children with atopic asthma. Sixty-seven of 186 genes also have significant asthma-associated methylation changes in nasal epithelia of adult white asthmatic patients. Conclusions: Epigenetic marks in respiratory epithelia are associated with allergic asthma and gene expression changes in inner-city children.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
DOIs
StateAccepted/In press - Sep 27 2015

Fingerprint

Nose
Asthma
Methylation
Epigenomics
Genes
Gene Expression
Respiratory Mucosa
DNA Methylation
Population
Nasal Mucosa
Economic Inflation
Cell Adhesion
African Americans
Extracellular Matrix
Immunity
Healthy Volunteers

Keywords

  • Atopic asthma
  • DNA methylation
  • Epigenetic regulation
  • Gene expression
  • Inner city
  • Microarray
  • Respiratory epithelia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Yang, I. V., Pedersen, B. S., Liu, A. H., O'Connor, G. T., Pillai, D., Kattan, M., ... Schwartz, D. A. (Accepted/In press). The nasal methylome and childhood atopic asthma. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2016.07.036

The nasal methylome and childhood atopic asthma. / Yang, Ivana V.; Pedersen, Brent S.; Liu, Andrew H.; O'Connor, George T.; Pillai, Dinesh; Kattan, Meyer; Misiak, Rana Tawil; Gruchalla, Rebecca; Szefler, Stanley J.; Khurana Hershey, Gurjit K.; Kercsmar, Carolyn; Richards, Adam; Stevens, Allen D.; Kolakowski, Christena A.; Makhija, Melanie; Sorkness, Christine A.; Krouse, Rebecca Z.; Visness, Cynthia; Davidson, Elizabeth J.; Hennessy, Corinne E.; Martin, Richard J.; Togias, Alkis; Busse, William W.; Schwartz, David A.

In: Journal of Allergy and Clinical Immunology, 27.09.2015.

Research output: Contribution to journalArticle

Yang, IV, Pedersen, BS, Liu, AH, O'Connor, GT, Pillai, D, Kattan, M, Misiak, RT, Gruchalla, R, Szefler, SJ, Khurana Hershey, GK, Kercsmar, C, Richards, A, Stevens, AD, Kolakowski, CA, Makhija, M, Sorkness, CA, Krouse, RZ, Visness, C, Davidson, EJ, Hennessy, CE, Martin, RJ, Togias, A, Busse, WW & Schwartz, DA 2015, 'The nasal methylome and childhood atopic asthma', Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2016.07.036
Yang, Ivana V. ; Pedersen, Brent S. ; Liu, Andrew H. ; O'Connor, George T. ; Pillai, Dinesh ; Kattan, Meyer ; Misiak, Rana Tawil ; Gruchalla, Rebecca ; Szefler, Stanley J. ; Khurana Hershey, Gurjit K. ; Kercsmar, Carolyn ; Richards, Adam ; Stevens, Allen D. ; Kolakowski, Christena A. ; Makhija, Melanie ; Sorkness, Christine A. ; Krouse, Rebecca Z. ; Visness, Cynthia ; Davidson, Elizabeth J. ; Hennessy, Corinne E. ; Martin, Richard J. ; Togias, Alkis ; Busse, William W. ; Schwartz, David A. / The nasal methylome and childhood atopic asthma. In: Journal of Allergy and Clinical Immunology. 2015.
@article{2aff958dfbb24ea49a83b2cbc8c08a4a,
title = "The nasal methylome and childhood atopic asthma",
abstract = "Background: Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma. Objective: We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma. Methods: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) versus healthy control subjects (n = 36). Results were validated in an independent population of asthmatic children (n = 30) by using a shared healthy control population (n = 36) and in an independent population of white adult atopic asthmatic patients (n = 12) and control subjects (n = 12). Results: We identified 186 genes with significant methylation changes, differentially methylated regions or differentially methylated probes, after adjustment for age, sex, race/ethnicity, batch effects, inflation, and multiple comparisons. Genes differentially methylated included those with established roles in asthma and atopy and genes related to extracellular matrix, immunity, cell adhesion, epigenetic regulation, and airflow obstruction. The methylation changes were substantial (median, 9.5{\%}; range, 2.6{\%} to 29.5{\%}). Hypomethylated and hypermethylated genes were associated with increased and decreased gene expression, respectively (P < 2.8 × 10-6 for differentially methylated regions and P < 7.8 × 10-10 for differentially methylated probes). Quantitative analysis in 53 differentially expressed genes demonstrated that 32 (60{\%}) have significant methylation-expression relationships within 5 kb of the gene. Ten loci selected based on the relevance to asthma, magnitude of methylation change, and methylation-expression relationships were validated in an independent cohort of children with atopic asthma. Sixty-seven of 186 genes also have significant asthma-associated methylation changes in nasal epithelia of adult white asthmatic patients. Conclusions: Epigenetic marks in respiratory epithelia are associated with allergic asthma and gene expression changes in inner-city children.",
keywords = "Atopic asthma, DNA methylation, Epigenetic regulation, Gene expression, Inner city, Microarray, Respiratory epithelia",
author = "Yang, {Ivana V.} and Pedersen, {Brent S.} and Liu, {Andrew H.} and O'Connor, {George T.} and Dinesh Pillai and Meyer Kattan and Misiak, {Rana Tawil} and Rebecca Gruchalla and Szefler, {Stanley J.} and {Khurana Hershey}, {Gurjit K.} and Carolyn Kercsmar and Adam Richards and Stevens, {Allen D.} and Kolakowski, {Christena A.} and Melanie Makhija and Sorkness, {Christine A.} and Krouse, {Rebecca Z.} and Cynthia Visness and Davidson, {Elizabeth J.} and Hennessy, {Corinne E.} and Martin, {Richard J.} and Alkis Togias and Busse, {William W.} and Schwartz, {David A.}",
year = "2015",
month = "9",
day = "27",
doi = "10.1016/j.jaci.2016.07.036",
language = "English (US)",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",

}

TY - JOUR

T1 - The nasal methylome and childhood atopic asthma

AU - Yang, Ivana V.

AU - Pedersen, Brent S.

AU - Liu, Andrew H.

AU - O'Connor, George T.

AU - Pillai, Dinesh

AU - Kattan, Meyer

AU - Misiak, Rana Tawil

AU - Gruchalla, Rebecca

AU - Szefler, Stanley J.

AU - Khurana Hershey, Gurjit K.

AU - Kercsmar, Carolyn

AU - Richards, Adam

AU - Stevens, Allen D.

AU - Kolakowski, Christena A.

AU - Makhija, Melanie

AU - Sorkness, Christine A.

AU - Krouse, Rebecca Z.

AU - Visness, Cynthia

AU - Davidson, Elizabeth J.

AU - Hennessy, Corinne E.

AU - Martin, Richard J.

AU - Togias, Alkis

AU - Busse, William W.

AU - Schwartz, David A.

PY - 2015/9/27

Y1 - 2015/9/27

N2 - Background: Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma. Objective: We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma. Methods: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) versus healthy control subjects (n = 36). Results were validated in an independent population of asthmatic children (n = 30) by using a shared healthy control population (n = 36) and in an independent population of white adult atopic asthmatic patients (n = 12) and control subjects (n = 12). Results: We identified 186 genes with significant methylation changes, differentially methylated regions or differentially methylated probes, after adjustment for age, sex, race/ethnicity, batch effects, inflation, and multiple comparisons. Genes differentially methylated included those with established roles in asthma and atopy and genes related to extracellular matrix, immunity, cell adhesion, epigenetic regulation, and airflow obstruction. The methylation changes were substantial (median, 9.5%; range, 2.6% to 29.5%). Hypomethylated and hypermethylated genes were associated with increased and decreased gene expression, respectively (P < 2.8 × 10-6 for differentially methylated regions and P < 7.8 × 10-10 for differentially methylated probes). Quantitative analysis in 53 differentially expressed genes demonstrated that 32 (60%) have significant methylation-expression relationships within 5 kb of the gene. Ten loci selected based on the relevance to asthma, magnitude of methylation change, and methylation-expression relationships were validated in an independent cohort of children with atopic asthma. Sixty-seven of 186 genes also have significant asthma-associated methylation changes in nasal epithelia of adult white asthmatic patients. Conclusions: Epigenetic marks in respiratory epithelia are associated with allergic asthma and gene expression changes in inner-city children.

AB - Background: Given the strong environmental influence on both epigenetic marks and allergic asthma in children, the epigenetic alterations in respiratory epithelia might provide insight into allergic asthma. Objective: We sought to identify DNA methylation and gene expression changes associated with childhood allergic persistent asthma. Methods: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma (n = 36) versus healthy control subjects (n = 36). Results were validated in an independent population of asthmatic children (n = 30) by using a shared healthy control population (n = 36) and in an independent population of white adult atopic asthmatic patients (n = 12) and control subjects (n = 12). Results: We identified 186 genes with significant methylation changes, differentially methylated regions or differentially methylated probes, after adjustment for age, sex, race/ethnicity, batch effects, inflation, and multiple comparisons. Genes differentially methylated included those with established roles in asthma and atopy and genes related to extracellular matrix, immunity, cell adhesion, epigenetic regulation, and airflow obstruction. The methylation changes were substantial (median, 9.5%; range, 2.6% to 29.5%). Hypomethylated and hypermethylated genes were associated with increased and decreased gene expression, respectively (P < 2.8 × 10-6 for differentially methylated regions and P < 7.8 × 10-10 for differentially methylated probes). Quantitative analysis in 53 differentially expressed genes demonstrated that 32 (60%) have significant methylation-expression relationships within 5 kb of the gene. Ten loci selected based on the relevance to asthma, magnitude of methylation change, and methylation-expression relationships were validated in an independent cohort of children with atopic asthma. Sixty-seven of 186 genes also have significant asthma-associated methylation changes in nasal epithelia of adult white asthmatic patients. Conclusions: Epigenetic marks in respiratory epithelia are associated with allergic asthma and gene expression changes in inner-city children.

KW - Atopic asthma

KW - DNA methylation

KW - Epigenetic regulation

KW - Gene expression

KW - Inner city

KW - Microarray

KW - Respiratory epithelia

UR - http://www.scopus.com/inward/record.url?scp=85008698604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008698604&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2016.07.036

DO - 10.1016/j.jaci.2016.07.036

M3 - Article

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

ER -