Newborn DNA methylation and asthma acquisition across adolescence and early adulthood
Newborn DNA methylation and asthma acquisition across adolescence and early adulthood
Background: Little is known about the association of newborn DNA methylation (DNAm) with asthma acquisition across adolescence and early adult life. Objective: We aim to identify epigenetic biomarkers in newborns for asthma acquisition during adolescence or young adulthood.
Methods: The Isle of Wight Birth Cohort (IOWBC) (n = 1456) data at ages 10, 18 and 26 years were assessed. To screen cytosine-phosphate-guanine site (CpGs) potentially associated with asthma acquisition, at the genome scale, we examined differentially methylated regions (DMR) using dmrff R package and individual CpG sites using linear regression on such associations. For CpGs that passed screening, we examined their enrichment in biological pathways using their mapping genes and tested their associations with asthma acquisitions using logistic regressions. Findings in IOWBC were tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.
Results: In total, 2636 unique CpGs passed screening, based on which we identified one biological pathway linked to asthma acquisition during adolescence in females (FDR adjusted p-value =.003 in IOWBC). Via logistic regressions, for females, four CpGs were shown to be associated with asthma acquisition during adolescence, and another four CpGs with asthma acquisition in young adulthood (FDR adjusted p-value <.05 in IOWBC) and these eight CpGs were replicated in ALSPAC (all p-values <.05). DNAm at all the identified CpGs was shown to be temporally consistent, and at six of the CpGs was associated with expressions of adjacent or mapping genes in females (all p-values <.05). For males, 622 CpGs were identified in IOWBC (FDR = 0.01), but these were not tested in ALSPAC due to small sample sizes.
Conclusion and clinical relevance: Eight CpGs on LHX5, IL22RA2, SOX11, CBX4, ACPT, CFAP46, MUC4, and ATP1B2 genes have the potential to serve as candidate epigenetic biomarkers in newborns for asthma acquisition in females during adolescence or young adulthood.
ALSPAC, Asthma acquisition, DNA methylation, Epigenome-wide, IOWBC
658-669
Li, Liang
419f8b8e-30ac-44e2-ad1f-c107ed2bb11e
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Syed Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Relton, Caroline L.
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
May 2022
Li, Liang
419f8b8e-30ac-44e2-ad1f-c107ed2bb11e
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Syed Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Relton, Caroline L.
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Li, Liang, Holloway, John W., Ewart, Susan, Arshad, Syed Hasan, Relton, Caroline L., Karmaus, Wilfried and Zhang, Hongmei
(2022)
Newborn DNA methylation and asthma acquisition across adolescence and early adulthood.
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 52 (5), .
(doi:10.1111/cea.14091).
Abstract
Background: Little is known about the association of newborn DNA methylation (DNAm) with asthma acquisition across adolescence and early adult life. Objective: We aim to identify epigenetic biomarkers in newborns for asthma acquisition during adolescence or young adulthood.
Methods: The Isle of Wight Birth Cohort (IOWBC) (n = 1456) data at ages 10, 18 and 26 years were assessed. To screen cytosine-phosphate-guanine site (CpGs) potentially associated with asthma acquisition, at the genome scale, we examined differentially methylated regions (DMR) using dmrff R package and individual CpG sites using linear regression on such associations. For CpGs that passed screening, we examined their enrichment in biological pathways using their mapping genes and tested their associations with asthma acquisitions using logistic regressions. Findings in IOWBC were tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.
Results: In total, 2636 unique CpGs passed screening, based on which we identified one biological pathway linked to asthma acquisition during adolescence in females (FDR adjusted p-value =.003 in IOWBC). Via logistic regressions, for females, four CpGs were shown to be associated with asthma acquisition during adolescence, and another four CpGs with asthma acquisition in young adulthood (FDR adjusted p-value <.05 in IOWBC) and these eight CpGs were replicated in ALSPAC (all p-values <.05). DNAm at all the identified CpGs was shown to be temporally consistent, and at six of the CpGs was associated with expressions of adjacent or mapping genes in females (all p-values <.05). For males, 622 CpGs were identified in IOWBC (FDR = 0.01), but these were not tested in ALSPAC due to small sample sizes.
Conclusion and clinical relevance: Eight CpGs on LHX5, IL22RA2, SOX11, CBX4, ACPT, CFAP46, MUC4, and ATP1B2 genes have the potential to serve as candidate epigenetic biomarkers in newborns for asthma acquisition in females during adolescence or young adulthood.
Text
3CEA_DNAm at birth and asthma acquistion_main_rev_12112021 HZ Resubmitted[43][57]
- Accepted Manuscript
More information
Accepted/In Press date: 3 January 2022
e-pub ahead of print date: 7 January 2022
Published date: May 2022
Additional Information:
Funding Information:
This work was supported by the National Institutes of Health research funds R01AI121226 (MPI: H Zhang and JW Holloway). DNAm analyses of F1 newborns and gene expression analyses of F2 newborns were funded by National Institute of Allergy and Infectious Diseases [R01 AI091905] and National Heart, Lung, and Blood Institute [R01 HL132321] (PI: W Karmaus). The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant‐acknowledgements.pdf ). CR is supported by the Medical Research Council and University of Bristol Integrative Epidemiology Unit (MC_UU_00011/5/MRC). The sponsor had no role in study design, data collection and analysis, or the preparation of the manuscript. This publication is the work of the authors, and Hongmei Zhang will serve as guarantor for the contents of this paper.
Publisher Copyright:
© 2022 John Wiley & Sons Ltd
Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.
Keywords:
ALSPAC, Asthma acquisition, DNA methylation, Epigenome-wide, IOWBC
Identifiers
Local EPrints ID: 456044
URI: http://eprints.soton.ac.uk/id/eprint/456044
ISSN: 0954-7894
PURE UUID: 1f348d65-9583-48c4-9f7f-86812b1cd8b7
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Date deposited: 12 Apr 2022 16:58
Last modified: 17 Mar 2024 07:12
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Contributors
Author:
Liang Li
Author:
Susan Ewart
Author:
Caroline L. Relton
Author:
Wilfried Karmaus
Author:
Hongmei Zhang
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