TY - JOUR
T1 - Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course
AU - den Dekker, Herman T.
AU - Burrows, Kimberley
AU - Felix, Janine F.
AU - Salas, Lucas A.
AU - Nedeljkovic, Ivana
AU - Yao, Jin
AU - Rifas-Shiman, Sheryl L.
AU - Ruiz-Arenas, Carlos
AU - Amin, N.
AU - Bustamante, Mariona
AU - DeMeo, Dawn L.
AU - John Henderson, A.
AU - Howe, Caitlin G.
AU - Hivert, Marie France
AU - Arfan Ikram, M.
AU - de Jongste, Johan C.
AU - Lahousse, Lies
AU - Mandaviya, Pooja R.
AU - van Meurs, Joyce B.
AU - Pinart, Mariona
AU - Sharp, Gemma C.
AU - Stolk, Lisette
AU - Uitterlinden, André G.
AU - Anto, Josep M.
AU - Litonjua, Augusto A.
AU - Breton, Carrie V.
AU - Brusselle, Guy G.
AU - Sunyer, Jordi
AU - Smith, George Davey
AU - Relton, Caroline L.
AU - Jaddoe, Vincent W.V.
AU - Duijts, Liesbeth
N1 - Publisher Copyright:
Copyright ©ERS 2019
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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-analysed 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) ratio and forced expiratory flow at 75% of FVC 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 nine with COPD in adulthood. Genes annotated to the top 10 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.
AB - 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-analysed 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) ratio and forced expiratory flow at 75% of FVC 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 nine with COPD in adulthood. Genes annotated to the top 10 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.
UR - https://www.scopus.com/pages/publications/85061964595
U2 - 10.1183/13993003.01795-2018
DO - 10.1183/13993003.01795-2018
M3 - Article
C2 - 30765504
AN - SCOPUS:85061964595
SN - 0903-1936
VL - 53
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 4
M1 - 1801795
ER -