DNA methylation and asthma acquisition during adolescence and post-adolescence, an epigenome-wide longitudinal study
DNA methylation and asthma acquisition during adolescence and post-adolescence, an epigenome-wide longitudinal study
The role of epigenetics in the pathogenesis of asthma acquisition in adolescence and post-adolescence has been unknown. We carried out a longitudinal epigenome-wide association study, using data from the Isle of Wight Birth Cohort (IOWBC). To improve statistical power, we first screened CpGs based on associations of DNA methylation (DNAm) at an age of 10 years (pre-ado-lescence) with asthma acquisition at 10–18 years (during adolescence). A logistic regression with repeated measures was applied to CpGs that passed screening to examine the associations of pre-adolescence DNAm with asthma acquisition from 10–18 years and 18–26 years, with an interaction term to evaluate transition period specificity. Findings were further tested in an independent birth cohort, ALSPAC. In total, 205 CpGs (with 150 being females) showed associations with asthma acquisition (main or interaction effects) at FDR = 0.05 in IOWBC, of which 112 (90 being females) showed consistent associations in the ALSPAC. Genes that the identified CpGs were mapped to, e.g., AKAP1 and ENO1, have been shown to be associated with the risk of asthma. Our findings indicated that DNAm at specific CpGs was associated with asthma acquisition. CpGs showing such associations were likely to be different between males and females and, at certain CpGs, were unique to a specific transition period.
ALSPAC, Asthma transition, DNA methylation, IOWBC, Sex-specificity
202
Rathod, Aniruddha
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Zhang, Hongmei
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Arshad, Syed Hasan
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Ewart, Susan
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Relton, Caroline L.
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Karmaus, Wilfried
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Holloway, John W.
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2 February 2022
Rathod, Aniruddha
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Zhang, Hongmei
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Arshad, Syed Hasan
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Ewart, Susan
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Relton, Caroline L.
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Karmaus, Wilfried
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Holloway, John W.
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Rathod, Aniruddha, Zhang, Hongmei, Arshad, Syed Hasan, Ewart, Susan, Relton, Caroline L., Karmaus, Wilfried and Holloway, John W.
(2022)
DNA methylation and asthma acquisition during adolescence and post-adolescence, an epigenome-wide longitudinal study.
Journal of Personalized Medicine, 12 (2), , [202].
(doi:10.3390/jpm12020202).
Abstract
The role of epigenetics in the pathogenesis of asthma acquisition in adolescence and post-adolescence has been unknown. We carried out a longitudinal epigenome-wide association study, using data from the Isle of Wight Birth Cohort (IOWBC). To improve statistical power, we first screened CpGs based on associations of DNA methylation (DNAm) at an age of 10 years (pre-ado-lescence) with asthma acquisition at 10–18 years (during adolescence). A logistic regression with repeated measures was applied to CpGs that passed screening to examine the associations of pre-adolescence DNAm with asthma acquisition from 10–18 years and 18–26 years, with an interaction term to evaluate transition period specificity. Findings were further tested in an independent birth cohort, ALSPAC. In total, 205 CpGs (with 150 being females) showed associations with asthma acquisition (main or interaction effects) at FDR = 0.05 in IOWBC, of which 112 (90 being females) showed consistent associations in the ALSPAC. Genes that the identified CpGs were mapped to, e.g., AKAP1 and ENO1, have been shown to be associated with the risk of asthma. Our findings indicated that DNAm at specific CpGs was associated with asthma acquisition. CpGs showing such associations were likely to be different between males and females and, at certain CpGs, were unique to a specific transition period.
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jpm-12-00202-v2
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Accepted/In Press date: 19 January 2022
Published date: 2 February 2022
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. R01 HL082925, H. Arshad), Asthma UK (Grant no. 364. S.H. Arshad), and the David Hide Asthma and Allergy Research Trust. None of the sponsors were involved in study design; collection, analysis, and interpretation of data; the writing of the manuscript; and the decision to submit the manuscript for publication. The authors are thankful to all the IOWBC participants and greatly appreciate the support of High-Performance Computing facility at the University of Memphis. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provided core support for ALSPAC. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/exter-nal/documents/grant-acknowledgements.pdf (accessed on 12 August 2019)). The 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, and MC_UU_12013/8.
Funding Information:
Funding: 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. R01 HL082925, H. Arshad), Asthma UK (Grant no. 364. S.H. Arshad), and the David Hide Asthma and Allergy Research Trust. None of the sponsors were involved in study design; collection, analysis, and interpretation of data; the writing of the manuscript; and the decision to submit the manuscript for publication. The authors are thankful to all the IOWBC participants and greatly appreciate the support of High-Performance Computing facility at the University of Memphis. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provided core support for ALSPAC. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf (accessed on 12 August 2019)). The 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, and MC_UU_12013/8.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.
Keywords:
ALSPAC, Asthma transition, DNA methylation, IOWBC, Sex-specificity
Identifiers
Local EPrints ID: 455700
URI: http://eprints.soton.ac.uk/id/eprint/455700
ISSN: 2075-4426
PURE UUID: a444e506-0134-46f8-a497-f9a4a47a7992
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Date deposited: 30 Mar 2022 17:04
Last modified: 17 Mar 2024 02:45
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Contributors
Author:
Aniruddha Rathod
Author:
Hongmei Zhang
Author:
Susan Ewart
Author:
Caroline L. Relton
Author:
Wilfried Karmaus
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