Abstract
Rationale We aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.
Methods We meta-analyzed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to Forced Expiratory Volume in 1 s (FEV1), FEV1/Forced Vital Capacity (FVC), and Forced Expiratory Flow at 75% of FVC (FEF75) at ages 7–13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.
Results We identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and 9 with COPD in adulthood. Genes annotated to the top ten identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.
Interpretation Our findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.
Footnotes
This 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. den Dekker has nothing to disclose.
Conflict of interest: Dr. Burrows has nothing to disclose.
Conflict of interest: Dr. Felix reports grants from European Union's Horizon 2020 research and innovation programme, during the conduct of the study.
Conflict of interest: Dr. Salas has nothing to disclose.
Conflict of interest: Dr. Nedeljkovic has nothing to disclose.
Conflict of interest: Dr. Yao has nothing to disclose.
Conflict of interest: Dr. Rifas-Shiman has nothing to disclose.
Conflict of interest: Dr. Amin has nothing to disclose.
Conflict of interest: Dr. Bustamante has nothing to disclose.
Conflict of interest: Dr. DeMeo reports grants from National Institutes of Health, and personal fees from Novartis for efforts outside the submitted work .
Conflict of interest: Dr. Howe has nothing to disclose.
Conflict of interest: Dr. Hivert has nothing to disclose.
Conflict of interest: Dr. de Jongste has nothing to disclose.
Conflict of interest: Dr. Lahousse has nothing to disclose.
Conflict of interest: Dr. Mandaviya has nothing to disclose.
Conflict of interest: Dr. van Meurs has nothing to disclose.
Conflict of interest: Dr. Pinart has nothing to disclose.
Conflict of interest: Dr. Sharp has nothing to disclose.
Conflict of interest: Dr. stolk has nothing to disclose.
Conflict of interest: Dr. Uitterlinden has nothing to disclose.
Conflict of interest: Dr. Antó has nothing to disclose.
Conflict of interest: Dr. Litonjua has nothing to disclose.
Conflict of interest: Dr. Breton has nothing to disclose.
Conflict of interest: Dr. Brusselle has nothing to disclose.
Conflict of interest: Dr. Sunyer has nothing to disclose.
Conflict of interest: Dr. Relton has nothing to disclose.
Conflict of interest: Dr. Jaddoe reports grants from European Union's Horizon 2020 research and innovation programme, during the conduct of the study.
Conflict of interest: Dr. Duijts reports grants from Lung Foundation, grants from Horizon 2020, personal fees from Abbvie, during the conduct of the study.
Conflict of interest: Dr. Ikram has nothing to disclose.
Conflict of interest: Dr. Ruiz Arenas has nothing to disclose.
Conflict of interest: Dr. Davey-Smith has nothing to disclose.
Conflict of interest: Dr. Henderson reports grants from Medical Research Council, grants from Wellcome, during the conduct of the study.
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