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Epigenome-wide association study of asthma and wheeze characterizes loci within HK1
BACKGROUND: To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood. METHODS: We performed epigenome-wide s...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657035/ https://www.ncbi.nlm.nih.gov/pubmed/31367216 http://dx.doi.org/10.1186/s13223-019-0356-z |
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author | Everson, Todd M. Zhang, Hongmei Lockett, Gabrielle A. Kaushal, Akhilesh Forthofer, Melinda Ewart, Susan L. Burrows, Kimberley Relton, Caroline L. Sharp, Gemma C. Henderson, A. John Patil, Veeresh K. Rezwan, Faisal I. Arshad, S. Hasan Holloway, John W. Karmaus, Wilfried |
author_facet | Everson, Todd M. Zhang, Hongmei Lockett, Gabrielle A. Kaushal, Akhilesh Forthofer, Melinda Ewart, Susan L. Burrows, Kimberley Relton, Caroline L. Sharp, Gemma C. Henderson, A. John Patil, Veeresh K. Rezwan, Faisal I. Arshad, S. Hasan Holloway, John W. Karmaus, Wilfried |
author_sort | Everson, Todd M. |
collection | PubMed |
description | BACKGROUND: To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood. METHODS: We performed epigenome-wide screening with recursive random forest feature selection and internal validation in the IOW birth cohort. We then tested whether we could replicate these findings in the independent cohort ALSPAC and followed-up our top finding with children of the IOW cohort. RESULTS: We identified 10 CpG sites associated with adolescent asthma at a 5% false discovery rate (IOW, n = 370), five of which exhibited evidence of associations in the replication study (ALSPAC, n = 720). One site, cg16658191, within HK1 displayed particularly strong associations after cellular heterogeneity adjustments in both cohorts (OR(IOW) = 0.17, 95% CI 0.04–0.57) (OR(ALSPAC) = 0.57, 95% CI 0.38–0.87). Additionally, higher expression of HK1 (OR = 3.81, 95% CI 1.41–11.77) in cord blood was predictive of wheezing in infancy (n = 82). CONCLUSION: We identified novel associations between asthma and wheeze with methylation at cg16658191 and the expression of HK1, which may serve as markers of, predictors of, and potentially etiologic factors involved in asthma and early life wheeze. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13223-019-0356-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6657035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66570352019-07-31 Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 Everson, Todd M. Zhang, Hongmei Lockett, Gabrielle A. Kaushal, Akhilesh Forthofer, Melinda Ewart, Susan L. Burrows, Kimberley Relton, Caroline L. Sharp, Gemma C. Henderson, A. John Patil, Veeresh K. Rezwan, Faisal I. Arshad, S. Hasan Holloway, John W. Karmaus, Wilfried Allergy Asthma Clin Immunol Research BACKGROUND: To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood. METHODS: We performed epigenome-wide screening with recursive random forest feature selection and internal validation in the IOW birth cohort. We then tested whether we could replicate these findings in the independent cohort ALSPAC and followed-up our top finding with children of the IOW cohort. RESULTS: We identified 10 CpG sites associated with adolescent asthma at a 5% false discovery rate (IOW, n = 370), five of which exhibited evidence of associations in the replication study (ALSPAC, n = 720). One site, cg16658191, within HK1 displayed particularly strong associations after cellular heterogeneity adjustments in both cohorts (OR(IOW) = 0.17, 95% CI 0.04–0.57) (OR(ALSPAC) = 0.57, 95% CI 0.38–0.87). Additionally, higher expression of HK1 (OR = 3.81, 95% CI 1.41–11.77) in cord blood was predictive of wheezing in infancy (n = 82). CONCLUSION: We identified novel associations between asthma and wheeze with methylation at cg16658191 and the expression of HK1, which may serve as markers of, predictors of, and potentially etiologic factors involved in asthma and early life wheeze. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13223-019-0356-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-24 /pmc/articles/PMC6657035/ /pubmed/31367216 http://dx.doi.org/10.1186/s13223-019-0356-z Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Everson, Todd M. Zhang, Hongmei Lockett, Gabrielle A. Kaushal, Akhilesh Forthofer, Melinda Ewart, Susan L. Burrows, Kimberley Relton, Caroline L. Sharp, Gemma C. Henderson, A. John Patil, Veeresh K. Rezwan, Faisal I. Arshad, S. Hasan Holloway, John W. Karmaus, Wilfried Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
title | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
title_full | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
title_fullStr | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
title_full_unstemmed | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
title_short | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
title_sort | epigenome-wide association study of asthma and wheeze characterizes loci within hk1 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657035/ https://www.ncbi.nlm.nih.gov/pubmed/31367216 http://dx.doi.org/10.1186/s13223-019-0356-z |
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