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DNA methylation at birth is associated with lung function development until age 26 years

DNA methylation at birth is associated with lung function development until age 26 years
DNA methylation at birth is associated with lung function development until age 26 years

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 in 1 s, forced vital capacity, their ratio, and forced expiratory flow at 25-75% of forced vital capacity) 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 focussed 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 eight 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, aged 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.

0903-1936
2003505
Mukherjee, Nandini
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Arathimos, Ryan
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Chen, Su
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Rahimabad, Parnian Kheirkhah
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Han, Luhang
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Zhang, Hongmei
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Holloway, John
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Relton, Caroline L.
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Henderson, A. John
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Arshad, Syed
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Ewart, Susan
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Karmaus, Wilifried
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Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Arathimos, Ryan
dd9cf1d5-d4d0-4338-a660-5aaf6f44b333
Chen, Su
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Rahimabad, Parnian Kheirkhah
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Han, Luhang
cfeafb0c-3b49-41ab-b05f-9cccf7573036
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Relton, Caroline L.
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Henderson, A. John
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Arshad, Syed
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Ewart, Susan
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Karmaus, Wilifried
057cf72f-addb-4911-ae51-3ee6f98a93ac

Mukherjee, Nandini, Arathimos, Ryan, Chen, Su, Rahimabad, Parnian Kheirkhah, Han, Luhang, Zhang, Hongmei, Holloway, John, Relton, Caroline L., Henderson, A. John, Arshad, Syed, Ewart, Susan and Karmaus, Wilifried (2021) DNA methylation at birth is associated with lung function development until age 26 years. European Respiratory Journal, 57 (4), 2003505, [2003505]. (doi:10.1183/13993003.03505-2020).

Record type: Article

Abstract

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 in 1 s, forced vital capacity, their ratio, and forced expiratory flow at 25-75% of forced vital capacity) 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 focussed 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 eight 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, aged 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.

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DNA methylation at birth is associated with lung function development till age 26 years ERJ-03505-2020 - Accepted Manuscript
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More information

Accepted/In Press date: 14 October 2020
e-pub ahead of print date: 19 November 2020
Published date: 15 April 2021

Identifiers

Local EPrints ID: 444662
URI: http://eprints.soton.ac.uk/id/eprint/444662
ISSN: 0903-1936
PURE UUID: eb061d02-11f9-4c21-8a1c-a051fe5173a0
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 28 Oct 2020 18:05
Last modified: 22 Nov 2021 08:16

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Contributors

Author: Nandini Mukherjee
Author: Ryan Arathimos
Author: Su Chen
Author: Parnian Kheirkhah Rahimabad
Author: Luhang Han
Author: Hongmei Zhang
Author: John Holloway ORCID iD
Author: Caroline L. Relton
Author: A. John Henderson
Author: Syed Arshad
Author: Susan Ewart
Author: Wilifried Karmaus

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