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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Research

Changes of DNA methylation are associated with changes in lung function during adolescence

Authors: Shadia Khan Sunny, Hongmei Zhang, Faisal I. Rezwan, Caroline L. Relton, A. John Henderson, Simon Kebede Merid, Erik Melén, Jenny Hallberg, S. Hasan Arshad, Susan Ewart, John W. Holloway

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs.

Methods

Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped.

Results

For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development.

Conclusions

The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.
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Metadata
Title
Changes of DNA methylation are associated with changes in lung function during adolescence
Authors
Shadia Khan Sunny
Hongmei Zhang
Faisal I. Rezwan
Caroline L. Relton
A. John Henderson
Simon Kebede Merid
Erik Melén
Jenny Hallberg
S. Hasan Arshad
Susan Ewart
John W. Holloway
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01342-y

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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