Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

Herman T den Dekker, Kimberley Burrows, Janine F Felix, Lucas A Salas, Ivana Nedeljkovic, Jin Yao, Sheryl L Rifas-Shiman, Carlos Ruiz-Arenas, N Amin, Mariona Bustamante, Dawn L DeMeo, A John Henderson, Caitlin G Howe, Marie-France Hivert, M Arfan Ikram, Johan C de Jongste, Lies Lahousse, Pooja R Mandaviya, Joyce B van Meurs, Mariona PinartGemma C Sharp, Lisette Stolk, André G Uitterlinden, Josep M Anto, Augusto A Litonjua, Carrie V Breton, Guy G Brusselle, Jordi Sunyer, George Davey Smith, Caroline L Relton, Vincent W V Jaddoe, Liesbeth Duijts

Research output: Contribution to journalArticleAcademicpeer-review

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-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.

Original languageEnglish
Article number1801795
Number of pages12
JournalEuropean Respiratory Journal
Volume53
Issue number4
DOIs
Publication statusPublished - 4 Apr 2019

Keywords

  • CORD BLOOD
  • OBSTRUCTIVE PULMONARY-DISEASE
  • ORIGINS
  • PATTERNS
  • PREDICTORS

Cite this

den Dekker, H. T., Burrows, K., Felix, J. F., Salas, L. A., Nedeljkovic, I., Yao, J., Rifas-Shiman, S. L., Ruiz-Arenas, C., Amin, N., Bustamante, M., DeMeo, D. L., Henderson, A. J., Howe, C. G., Hivert, M-F., Ikram, M. A., de Jongste, J. C., Lahousse, L., Mandaviya, P. R., van Meurs, J. B., ... Duijts, L. (2019). Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course. European Respiratory Journal, 53(4), [1801795]. https://doi.org/10.1183/13993003.01795-2018