DNA methylation at birth is associated with lung function development until age 26 years

Abstract

Little is known about whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites at birth predicts patterns of lung function development. We used heel prick DNAm from the F1-generation of Isle of Wight birth cohort (IOWBC-F1) for discovery of CpGs associated with lung function trajectories (Forced Expiratory Volume, Forced Vital Capacity, their ratio, and Forced Expiratory Flow at 25–75%) over the first 26 years, stratified by sex. We replicated the findings in the Avon Longitudinal Study of Parents and Children (ALSPAC) using cord blood DNAm.Epigenome-wide screening was applied to identify CpGs associated with lung function trajectories in 396 boys, and 390 girls of IOWBC-F1. Replication in ALSPAC focused on lung function at ages 8, 15 and 24 years. Statistically significantly replicated CpGs were investigated for consistency in direction of association between cohorts, stability of DNAm over time in IOWBC-F1, relevant biological processes, and for association with gene expression (n=161) in IOWBC F2-generation (IOWBC-F2).Differential DNAm of 8 CpGs on genes GLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6, and WNT11 involved in developmental processes, were significantly associated with lung function in the same direction in IOWBC-F1 and ALSPAC, and showed stable patterns at birth, age 10 and 18 years between high and low lung function trajectories in IOWBC-F1. CpGs on LHX1 and COL18A1 were linked to gene expression in IOWBC-F2.In two large cohorts, novel DNAm at birth were associated with patterns of lung function in adolescence and early adulthood providing possible targets for preventative interventions against adverse pulmonary function development.

Predictors of lung function trajectories in population‐based studies: A systematic review

“…Spirometry was the primary lung function measurement used in all studies included. Eight studies conducted spirometry according to the American Thoracic Society/European Respiratory Society guidelines 3,18–24 . Eight studies reported pre‐bronchodilator measures 3,17–21,24 while one reported both pre‐ and post‐bronchodilator measures 18 .…”

“…18 Epigenome-wide associations of DNA-methylation (DNA-M) at specific cytosine phosphate-guanine dinucleotide sites (CpGs) at birth and at age 7 years were observed to be associated with lung function trajectories in two studies. IOW 22,23 and ALSPAC 23 observed DNA-M of eight CpGs on genes GLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6 and WNT11 at birth and DNA-M at 44 distinct CpGs mapped with 42 genes to be associated with FEV 1 , FVC and FEV 1 /FVC trajectories between ages 10 and 26 years, 22,23 respectively. (Tables 2 and S6 in the Supporting Information).…”

Promotor Hypomethylation Mediated Upregulation of miR-23b-3p Targets PTEN to Promote Bronchial Epithelial-Mesenchymal Transition in Chronic Asthma

“…However, research on non-coding RNA regulated by DNA methylation in asthma is scarce. The regulation of miRNA expression by DNA methylation has been reported in many diseases of cancer, but not in asthma (18,19). For example, Tao et al have demonstrated that methylation-mediated inhibition of miR-497 promoted the progression of breast cancer (20).…”

“…However, research on non-coding RNA regulated by DNA methylation in asthma is scarce. The regulation of miRNA expression by DNA methylation has been reported in many diseases of cancer, but not in asthma ( 18 , 19 ). For example, Tao et al.…”

Exposure to Stress and Air Pollution from Bushfires during Pregnancy: Could Epigenetic Changes Explain Effects on the Offspring?

“…A recent study of two population-based cohorts showed differential blood DNAm of 8 CpG sites in 8 genes related to development and lung morphogenesis at birth, which were associated with lung function trajectories over the first 26 years of life [ 60 ]. This was the first study to examine health trajectories across a significant period of time, specifically at ages 10, 18, and 26 years in the Isle of Wight birth cohort, and ages 8, 15, and 24 years in the ALSPAC cohort.…”