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. 2020 Apr 7;21(1):80.
doi: 10.1186/s12931-020-01342-y.

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

Shadia Khan Sunny  1 , Hongmei Zhang  2 , Faisal I Rezwan  3 , Caroline L Relton  4 , A John Henderson  5 , Simon Kebede Merid  6 , Erik Melén  6   7 , Jenny Hallberg  6   7 , S Hasan Arshad  8   9 , Susan Ewart  10 , John W Holloway  11
Affiliations

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

Shadia Khan Sunny et al. Respir Res. .

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.

Keywords: ALSPAC; Adolescence; BAMSE; DNA methylation; Genome-wide; IOW cohort; Lung function.

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Conflict of interest statement

The authors declare that they have no potential competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of statistical analyses and the number of CpGs after each analysis. Note: 1) *Number of significant CpGs were mentioned in an order for FVC, FEV1, and FEV1/ FVC changes respectively. 2) **At age 10 years, for males, between FVC and FEV1, and between FEV1 and FEV1/ FVC, 8 and 3 CpGs are overlapped, respectively; for females, between FVC and FEV1, 21 CpGs are overlapped in the screening. 3) At age 18 years, for males, between FVC and FEV1, and between FEV1 and FEV1 / FVC, 8 and 1 CpGs are overlapped, respectively; for females, between FVC and FEV1, between FEV1 and FEV1/ FVC, and between FVC and FEV1/ FVC, 9, 1, and 2 CpGs are overlapped, respectively, in the screening
Fig. 2
Fig. 2
Barplots of coefficients of IOW-ALSPAC and IOW-BAMSE consistent CpGs with their mapped genes in females. Note: The coefficients were shown for the association of DNA-M changes with changes in lung function (FEV1/FVC) in females adolescence. Mapped genes of the CpGs showing consistent associations between the IOW and ALSPAC cohorts (left panels) and between the IOW and BAMSE cohorts (right panels) were included. Gene names overlapped among the three cohorts were given in red font
See this image and copyright information in PMC

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