Changes of DNA methylation and their association with changes in lung function during adolescence - an epigenome-wide study

RATIONALE: Prior studies showed that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine sites (CpGs) changes over time. Lung function (LF) changes during adolescence. Little is known about the modification of LF-specific DNA-M during adolescence. We hypothesized that changes in DNA-M across adolescence is associated with changes in LF.

METHODS: DNA-M was measured in peripheral blood samples collected at ages 10 (n = 329) and 18 years (n = 476) from the Isle of Wight birth cohort (UK) using Illumina Infinium HumanMethylation450 and EPIC Beadchips. Spirometry was conducted at both ages. A training and testing method (ttScreening) was used to screen 439,635 CpGs. Linear regressions were applied to assess the association of LF (FVC, FEV₁ and FEV₁/FVC) changes with DNA-M changes, adjusted for adolescence-related and personal and family-related confounders.

RESULTS: In total 191 CpGs (84, 73, and 85 CpGs for FVC, FEV₁ and FEV₁/FVC respectively) were identified (p values <0.05), with 21 CpGs associated with change of both FVC and FEV₁ (same direction), 8 with FVC and FEV₁/ FVC (opposite direction), 20 with FEV₁ and FEV₁/FVC (same direction). DNA-M change at cg02648581 corresponding to an intergenic site was associated with changes of all three measures in different directions. Five CpGs for FVC, 3 for FEV₁/ FVC, and none for FEV₁ survived multiple testing at FDR=0.15.

CONCLUSIONS: CpGs identified from this study may serve as epigenetic markers for lung function changes during adolescence. The findings will be replicated in an independent study, the ALSPAC cohort.