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Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood
BACKGROUND: The pattern of lung function development from pre-adolescence to adulthood plays a significant role in the pathogenesis of respiratory diseases. Inconsistent findings in genetic studies on lung function trajectories, the importance of DNA methylation (DNA-M), and the critical role of ado...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789734/ https://www.ncbi.nlm.nih.gov/pubmed/33407823 http://dx.doi.org/10.1186/s13148-020-00992-5 |
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author | Sunny, Shadia Khan Zhang, Hongmei Mzayek, Fawaz Relton, Caroline L. Ring, Susan Henderson, A. John Ewart, Susan Holloway, John W. Arshad, S. Hasan |
author_facet | Sunny, Shadia Khan Zhang, Hongmei Mzayek, Fawaz Relton, Caroline L. Ring, Susan Henderson, A. John Ewart, Susan Holloway, John W. Arshad, S. Hasan |
author_sort | Sunny, Shadia Khan |
collection | PubMed |
description | BACKGROUND: The pattern of lung function development from pre-adolescence to adulthood plays a significant role in the pathogenesis of respiratory diseases. Inconsistent findings in genetic studies on lung function trajectories, the importance of DNA methylation (DNA-M), and the critical role of adolescence in lung function development motivated the present study of pre-adolescent DNA-M with lung function trajectories. This study investigated epigenome-wide associations of DNA-M at cytosine-phosphate-guanine dinucleotide sites (CpGs) at childhood with lung function trajectories from childhood to young adulthood. METHODS: DNA-M was measured in peripheral blood at age 10 years in the Isle of Wight (IOW) birth cohort. Spirometry was conducted at ages 10, 18, and 26 years. A training/testing-based method was used to screen CpGs. Multivariable logistic regressions were applied to assess the association of DNA-M with lung function trajectories from pre-adolescence to adulthood. To detect differentially methylated regions (DMRs) among CpGs, DMR enrichment analysis was conducted. Findings were further tested in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Pathway analyses were performed on the mapped genes of the identified CpGs and DMRs. Biological relevance of the identified CpGs was assessed with gene expression. All analyses were stratified by sex. RESULTS: High and low trajectories of FVC, FEV(1), and FEV(1)/FVC in each sex were identified. At P(Bonferroni) < 0.05, DNA-M at 96 distinct CpGs (41 in males) showed associations with FVC, FEV(1), and FEV(1)/FVC trajectories in IOW cohort. These 95 CpGs (cg24000797 was disqualified) were further tested in ALSPAC; 44 CpGs (19 in males) of these 95 showed the same directions of association as in the IOW cohort; and three CpGs (two in males) were replicated. DNA-M at two and four CpGs showed significant associations with the corresponding gene expression in males and females, respectively. At P(FDR) < 0.05, 23 and 10 DMRs were identified in males and females, respectively. Pathways were identified; some of those were linked to lung function and chronic obstructive lung diseases. CONCLUSION: The identified CpGs at pre-adolescence have the potential to serve as candidate markers for lung function trajectory prediction and chronic lung diseases. |
format | Online Article Text |
id | pubmed-7789734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-77897342021-01-07 Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood Sunny, Shadia Khan Zhang, Hongmei Mzayek, Fawaz Relton, Caroline L. Ring, Susan Henderson, A. John Ewart, Susan Holloway, John W. Arshad, S. Hasan Clin Epigenetics Research BACKGROUND: The pattern of lung function development from pre-adolescence to adulthood plays a significant role in the pathogenesis of respiratory diseases. Inconsistent findings in genetic studies on lung function trajectories, the importance of DNA methylation (DNA-M), and the critical role of adolescence in lung function development motivated the present study of pre-adolescent DNA-M with lung function trajectories. This study investigated epigenome-wide associations of DNA-M at cytosine-phosphate-guanine dinucleotide sites (CpGs) at childhood with lung function trajectories from childhood to young adulthood. METHODS: DNA-M was measured in peripheral blood at age 10 years in the Isle of Wight (IOW) birth cohort. Spirometry was conducted at ages 10, 18, and 26 years. A training/testing-based method was used to screen CpGs. Multivariable logistic regressions were applied to assess the association of DNA-M with lung function trajectories from pre-adolescence to adulthood. To detect differentially methylated regions (DMRs) among CpGs, DMR enrichment analysis was conducted. Findings were further tested in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Pathway analyses were performed on the mapped genes of the identified CpGs and DMRs. Biological relevance of the identified CpGs was assessed with gene expression. All analyses were stratified by sex. RESULTS: High and low trajectories of FVC, FEV(1), and FEV(1)/FVC in each sex were identified. At P(Bonferroni) < 0.05, DNA-M at 96 distinct CpGs (41 in males) showed associations with FVC, FEV(1), and FEV(1)/FVC trajectories in IOW cohort. These 95 CpGs (cg24000797 was disqualified) were further tested in ALSPAC; 44 CpGs (19 in males) of these 95 showed the same directions of association as in the IOW cohort; and three CpGs (two in males) were replicated. DNA-M at two and four CpGs showed significant associations with the corresponding gene expression in males and females, respectively. At P(FDR) < 0.05, 23 and 10 DMRs were identified in males and females, respectively. Pathways were identified; some of those were linked to lung function and chronic obstructive lung diseases. CONCLUSION: The identified CpGs at pre-adolescence have the potential to serve as candidate markers for lung function trajectory prediction and chronic lung diseases. BioMed Central 2021-01-06 /pmc/articles/PMC7789734/ /pubmed/33407823 http://dx.doi.org/10.1186/s13148-020-00992-5 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. |
spellingShingle | Research Sunny, Shadia Khan Zhang, Hongmei Mzayek, Fawaz Relton, Caroline L. Ring, Susan Henderson, A. John Ewart, Susan Holloway, John W. Arshad, S. Hasan Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood |
title | Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood |
title_full | Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood |
title_fullStr | Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood |
title_full_unstemmed | Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood |
title_short | Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood |
title_sort | pre-adolescence dna methylation is associated with lung function trajectories from pre-adolescence to adulthood |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789734/ https://www.ncbi.nlm.nih.gov/pubmed/33407823 http://dx.doi.org/10.1186/s13148-020-00992-5 |
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