Sex‐specific associations of asthma acquisition with changes in DNA methylation during adolescence
Sex‐specific associations of asthma acquisition with changes in DNA methylation during adolescence
Background: Underlying biological mechanisms involved in sex differences in asthma status changes from pre- to post-adolescence are unclear. DNA methylation (DNAm) has been shown to be associated with the risk of asthma. Objective: We hypothesized that asthma acquisition from pre- to post-adolescence was associated with changes in DNAm during this period at asthma-associated cytosine-phosphate-guanine (CpG) sites and such an association was sex-specific. Methods: Subjects from the Isle of Wight birth cohort (IOWBC) with DNAm in blood at ages 10 and 18 years (n = 124 females, 151 males) were studied. Using a training-testing approach, epigenome-wide CpGs associated with asthma were identified. Logistic regression was used to examine sex-specific associations of DNAm changes with asthma acquisition between ages 10 and 18 at asthma-associated CpGs. The ALSPAC birth cohort was used for independent replication. To assess functional relevance of identified CpGs, association of DNAm with gene expression in blood was assessed. Results: We identified 535 CpGs potentially associated with asthma. Significant interaction effects of DNAm changes and sex on asthma acquisition in adolescence were found at 13 of the 535 CpGs in IOWBC (P-values <1.0 × 10
−3). In the replication cohort, consistent interaction effects were observed at 10 of the 13 CpGs. At 7 of these 10 CpGs, opposite DNAm changes across adolescence were observed between sexes in both cohorts. In both cohorts, cg20891917, located on IFRD1 linked to asthma, shows strong sex-specific effects on asthma transition (P-values <.01 in both cohorts). Conclusion and clinical relevance: Gender reversal in asthma acquisition is associated with opposite changes in DNAm (males vs females) from pre- to post-adolescence at asthma-associated CpGs. These CpGs are potential biomarkers of sex-specific asthma acquisition in adolescence.
ALSPAC, DNA methylation, IOWBC, asthma acquisition, sex-specificity
318-328
Patel, Rutu
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Solatikia, Farnaz
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Zhang, Hongmei
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Wolde, Alemayehu
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Perunthadambil Kadalayil, Latha
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Karmaus, Wilfried
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Ewart, Susan
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Arathimos, Ryan
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Relton, Caroline
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Ring, Susan
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Henderson, A. John
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Arshad, Syed
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Holloway, John W
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4 November 2020
Patel, Rutu
291b880a-bd26-4649-9124-f1577d4f5002
Solatikia, Farnaz
3f9a7471-8c3c-4da2-b3ba-7dd2c81695cc
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Wolde, Alemayehu
d62938ab-efb6-4967-a74e-13f663147ade
Perunthadambil Kadalayil, Latha
e620b801-844a-45d9-acaf-e0a58acd7cf2
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arathimos, Ryan
dd9cf1d5-d4d0-4338-a660-5aaf6f44b333
Relton, Caroline
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Ring, Susan
79941daa-7ae8-47f1-beb4-e8560ce12fd8
Henderson, A. John
03d06941-3f2c-4a2e-998b-8d18124049d1
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Patel, Rutu, Solatikia, Farnaz, Zhang, Hongmei, Wolde, Alemayehu, Perunthadambil Kadalayil, Latha, Karmaus, Wilfried, Ewart, Susan, Arathimos, Ryan, Relton, Caroline, Ring, Susan, Henderson, A. John, Arshad, Syed and Holloway, John W
(2020)
Sex‐specific associations of asthma acquisition with changes in DNA methylation during adolescence.
Clinical & Experimental Allergy, 51 (2), .
(doi:10.1111/cea.13776).
Abstract
Background: Underlying biological mechanisms involved in sex differences in asthma status changes from pre- to post-adolescence are unclear. DNA methylation (DNAm) has been shown to be associated with the risk of asthma. Objective: We hypothesized that asthma acquisition from pre- to post-adolescence was associated with changes in DNAm during this period at asthma-associated cytosine-phosphate-guanine (CpG) sites and such an association was sex-specific. Methods: Subjects from the Isle of Wight birth cohort (IOWBC) with DNAm in blood at ages 10 and 18 years (n = 124 females, 151 males) were studied. Using a training-testing approach, epigenome-wide CpGs associated with asthma were identified. Logistic regression was used to examine sex-specific associations of DNAm changes with asthma acquisition between ages 10 and 18 at asthma-associated CpGs. The ALSPAC birth cohort was used for independent replication. To assess functional relevance of identified CpGs, association of DNAm with gene expression in blood was assessed. Results: We identified 535 CpGs potentially associated with asthma. Significant interaction effects of DNAm changes and sex on asthma acquisition in adolescence were found at 13 of the 535 CpGs in IOWBC (P-values <1.0 × 10
−3). In the replication cohort, consistent interaction effects were observed at 10 of the 13 CpGs. At 7 of these 10 CpGs, opposite DNAm changes across adolescence were observed between sexes in both cohorts. In both cohorts, cg20891917, located on IFRD1 linked to asthma, shows strong sex-specific effects on asthma transition (P-values <.01 in both cohorts). Conclusion and clinical relevance: Gender reversal in asthma acquisition is associated with opposite changes in DNAm (males vs females) from pre- to post-adolescence at asthma-associated CpGs. These CpGs are potential biomarkers of sex-specific asthma acquisition in adolescence.
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More information
Accepted/In Press date: 8 October 2020
e-pub ahead of print date: 4 November 2020
Published date: 4 November 2020
Additional Information:
Funding Information:
This study was supported by the National Institutes of Health research fund R01AI121226 (MPI: H Zhang and JW Holloway). Part of the methylation data generation was supported by R01AI091905 (PI: W Karmaus). The Isle of Wight Birth Cohort assessments have been supported by the National Institutes of Health USA (Grant no. R01HL082925, H. Arshad), Asthma UK (Grant no. 364. SH Arshad) and the David Hide Asthma and Allergy Research Trust.
Funding Information:
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 ). Generation of methylation array data was specifically funded by NIH R01AI121226, R01AI091905, BBSRC BBI025751/1 and BB/I025263/1, MRC MC_UU_12013/1, MC_UU_12013/2, MC_UU_12013/8.
Publisher Copyright:
© 2020 John Wiley & Sons Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
Keywords:
ALSPAC, DNA methylation, IOWBC, asthma acquisition, sex-specificity
Identifiers
Local EPrints ID: 445095
URI: http://eprints.soton.ac.uk/id/eprint/445095
ISSN: 0954-7894
PURE UUID: 3f1e20b5-89ca-489f-b378-c736a235d1da
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Date deposited: 19 Nov 2020 17:32
Last modified: 17 Mar 2024 06:04
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Contributors
Author:
Rutu Patel
Author:
Farnaz Solatikia
Author:
Hongmei Zhang
Author:
Alemayehu Wolde
Author:
Wilfried Karmaus
Author:
Susan Ewart
Author:
Ryan Arathimos
Author:
Caroline Relton
Author:
Susan Ring
Author:
A. John Henderson
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