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Eur Respir J. 2019 Apr 4;53(4). pii: 1801795. doi: 10.1183/13993003.01795-2018. Print 2019 Apr.

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

Author information

1
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
2
Dept of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
3
Dept of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
4
These authors contributed equally.
5
MRC Integrative Epidemiology Unit, University of Bristol, UK School of Social and Community Medicine, University of Bristol, Bristol, UK.
6
Dept of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
7
ISGLobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
8
Dept of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
9
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
10
CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
11
Dept of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
12
Obesity Prevention Program, Dept of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
13
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
14
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
15
Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
16
Dept of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
17
Dept of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
18
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
19
Netherlands Consortium for Healthy Ageing (NCHA), Erasmus MC, University Medical Center Rotterdam, The Netherlands.
20
Dept of Respiratory Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
21
Dept of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands l.duijts@erasmusmc.nl.
22
Dept of Pediatrics, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

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.

Conflict of interest statement

Conflict of interest: H.T. den Dekker has nothing to disclose. Conflict of interest: K. Burrows has nothing to disclose. Conflict of interest: J.F. Felix reports funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 633595 (DynaHEALTH). The Generation R Study received funding from the European Union's Horizon 2020 research and innovation programme (733206, LIFECYCLE). Conflict of interest: L.A. Salas has nothing to disclose. Conflict of interest: I. Nedeljkovic has nothing to disclose. Conflict of interest: J. Yao has nothing to disclose. Conflict of interest: S.L. Rifas-Shiman has nothing to disclose. Conflict of interest: V. Ruiz-Arenas has nothing to disclose. Conflict of interest: N. Amin has nothing to disclose. Conflict of interest: M. Bustamante has nothing to disclose. Conflict of interest: D.L. DeMeo reports grants from National Institutes of Health, and personal fees from Novartis, outside the submitted work. Conflict of interest: A.J. Henderson reports grants from Medical Research Council and Wellcome, during the conduct of the study. Conflict of interest: C.G. Howe has nothing to disclose. Conflict of interest: M-F. Hivert has nothing to disclose. Conflict of interest: M.A. Ikram has nothing to disclose. Conflict of interest: J.C. de Jongste has nothing to disclose. Conflict of interest: L. Lahousse has nothing to disclose. Conflict of interest: P.R. Mandaviya has nothing to disclose. Conflict of interest: J.B. van Meurs has nothing to disclose. Conflict of interest: M. Pinart has nothing to disclose. Conflict of interest: G.C. Sharp has nothing to disclose. Conflict of interest: L. Stolk has nothing to disclose. Conflict of interest: A.G. Uitterlinden has nothing to disclose. Conflict of interest: J.M. Antó has nothing to disclose. Conflict of interest: A.A. Litonjua has nothing to disclose. Conflict of interest: C.V. Breton has nothing to disclose. Conflict of interest: G.G. Brusselle has nothing to disclose. Conflict of interest: J. Sunyer has nothing to disclose. Conflict of interest: G.D. Smith has nothing to disclose. Conflict of interest: C.L. Relton has nothing to disclose. Conflict of interest: V.W.V. Jaddoe reports funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 633595 (DynaHEALTH). The Generation R Study received funding from the European Union's Horizon 2020 research and innovation programme (733206, LIFECYCLE). Conflict of interest: L. Duijts reports grants from Lung Foundation Netherlands and from the European Union's Horizon 2020 research and innovation programme under grant agreement number 733206 (LIFECYCLE), and speaker fees for the CIPP2016 conference from Abbvie, during the conduct of the study.

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