%0 Journal Article %A Nandini Mukherjee %A Ryan Arathimos %A Su Chen %A Parnian Kheirkhah Rahimabad %A Luhang Han %A Hongmei Zhang %A John W. Holloway %A Caroline Relton %A A. John Henderson %A Syed Hasan Arshad %A Susan Ewart %A Wilfried Karmaus %T DNA methylation at birth is associated with lung function development till age 26 years %D 2020 %R 10.1183/13993003.03505-2020 %J European Respiratory Journal %P 2003505 %X 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Yan reports grants from National Institutes of Health, during the conduct of the study;.Conflict of interest: Dr. Mukherjee has nothing to disclose.Conflict of interest: Dr. Arathimos has nothing to disclose.Conflict of interest: Dr. Chen has nothing to disclose.Conflict of interest: Dr. Kheirkhah Rahimabad has nothing to disclose.Conflict of interest: Ms. Han has nothing to disclose.Conflict of interest: Dr. Zhang has nothing to disclose.Conflict of interest: Dr. Holloway reports grants from the National institutes of Health (USA), during the conduct of the study;.Conflict of interest: Dr. Relton has nothing to disclose.Conflict of interest: Dr. Arshad has nothing to disclose.Conflict of interest: Dr. Ewart has nothing to disclose.Conflict of interest: Dr. Karmaus has nothing to disclose. %U https://erj.ersjournals.com/content/erj/early/2020/10/15/13993003.03505-2020.full.pdf