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; Richard J. Martin; Alkis Togias; William W. Busse; David A. Schwartz

doi:10.1016/j.jaci.2016.07.036

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. HennessyRichard J. Martin, Alkis Togias, William W. Busse, David A. Schwartz

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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 language	English (US)
Pages (from-to)	1478-1488
Number of pages	11
Journal	Journal of Allergy and Clinical Immunology
Volume	139
Issue number	5
DOIs	https://doi.org/10.1016/j.jaci.2016.07.036
State	Published - May 2017

Keywords

DNA methylation
atopic asthma
epigenetic regulation
gene expression
inner city
microarray
respiratory epithelia

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.jaci.2016.07.036

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Yang, I. V., Pedersen, B. S., Liu, A. H., O'Connor, G. T., Pillai, D., Kattan, M., Misiak, R. T., Gruchalla, R., Szefler, S. J., Khurana Hershey, G. K., Kercsmar, C., Richards, A., Stevens, A. D., Kolakowski, C. A., Makhija, M., Sorkness, C. A., Krouse, R. Z., Visness, C., Davidson, E. J., ... Schwartz, D. A. (2017). The nasal methylome and childhood atopic asthma. Journal of Allergy and Clinical Immunology, 139(5), 1478-1488. https://doi.org/10.1016/j.jaci.2016.07.036

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 2017, 'The nasal methylome and childhood atopic asthma', Journal of Allergy and Clinical Immunology, vol. 139, no. 5, pp. 1478-1488. https://doi.org/10.1016/j.jaci.2016.07.036

@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 = "DNA methylation, atopic asthma, 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.}",

note = "Publisher Copyright: {\textcopyright} 2016 American Academy of Allergy, Asthma & Immunology",

year = "2017",

month = may,

doi = "10.1016/j.jaci.2016.07.036",

language = "English (US)",

volume = "139",

pages = "1478--1488",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "5",

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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 - 2017/5

Y1 - 2017/5

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 - DNA methylation

KW - atopic asthma

KW - epigenetic regulation

KW - gene expression

KW - inner city

KW - microarray

KW - respiratory epithelia

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VL - 139

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JO - Journal of Allergy and Clinical Immunology

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ER -

The nasal methylome and childhood atopic asthma

Abstract

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