Changes of DNA methylation are associated with changes in lung function during adolescence.
ALSPAC
Adolescence
BAMSE
DNA methylation
Genome-wide
IOW cohort
Lung function
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
07 Apr 2020
07 Apr 2020
Historique:
received:
03
12
2019
accepted:
25
03
2020
entrez:
9
4
2020
pubmed:
9
4
2020
medline:
30
1
2021
Statut:
epublish
Résumé
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. 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. For females, 42 CpGs showed statistically significant associations with change in FEV 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
For females, 42 CpGs showed statistically significant associations with change in FEV
CONCLUSIONS
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.
Identifiants
pubmed: 32264874
doi: 10.1186/s12931-020-01342-y
pii: 10.1186/s12931-020-01342-y
pmc: PMC7140357
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
80Subventions
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : UK Medical Research Council (MRC) and Wellcome
ID : 102215/2/13/2
Organisme : NIAID NIH HHS
ID : R01 AI121226
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12013/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/5
Pays : United Kingdom
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