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

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dc.contributor.authorSunny, Shadia Khan
dc.contributor.authorZhang, Hongmei
dc.contributor.authorRezwan, Faisal I.
dc.contributor.authorRelton, Caroline L.
dc.contributor.authorHenderson, A. John
dc.contributor.authorMerid, Simon Kebede
dc.contributor.authorMelén, Erik
dc.contributor.authorHallberg, Jenny
dc.contributor.authorArshad, Syed Hasan
dc.contributor.authorEwart, Susan
dc.contributor.authorHolloway, John W.
dc.date.accessioned2020-08-05T10:35:19Z
dc.date.available2020-08-05T10:35:19Z
dc.date.issued2020-04-07
dc.description.abstractBackground 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 femalesen_UK
dc.identifier.citationSunny SK, Zhang H, Rezwan FI, et al., (2020) Changes of DNA methylation are associated with changes in lung function during adolescence. Respiratory Research, Volume 21, 2020, Article number 80en_UK
dc.identifier.issn1465-9921
dc.identifier.urihttps://doi.org/10.1186/s12931-020-01342-y
dc.identifier.urihttp://dspace.lib.cranfield.ac.uk/handle/1826/15638
dc.language.isoenen_UK
dc.publisherBioMed Centralen_UK
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectLung functionen_UK
dc.subjectIOW cohorten_UK
dc.subjectGenome-wideen_UK
dc.subjectDNA methylationen_UK
dc.subjectBAMSEen_UK
dc.subjectAdolescenceen_UK
dc.subjectALSPACen_UK
dc.titleChanges of DNA methylation are associated with changes in lung function during adolescenceen_UK
dc.typeArticleen_UK

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