BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA Methylation
BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA Methylation
Purpose: body mass index (BMI) is associated with asthma but associations of BMI temporal patterns with asthma incidence are unclear. Previous studies suggest that DNA methylation (DNAm) is associated with asthma status and variation in DNAm is a consequence of BMI changes. This study assessed the direct and indirect (via DNAm) effects of BMI trajectories in childhood on asthma incidence at young adulthood.
Methods: data from the Isle of Wight (IoW) birth cohort were included in the analyses. Group-based trajectory modelling was applied to infer latent BMI trajectories from ages 1 to 10 years. An R package, ttscreening, was applied to identify differentially methylated CpGs at age 10 years associated with BMI trajectories, stratified for sex. Logistic regressions were used to further exclude CpGs with DNAm at age 10 years not associated with asthma incidence at 18 years. CpGs discovered via path analyses that mediated the association of BMI trajectories with asthma incidence in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Children and Parents (ALSPAC).
Results: two BMI trajectories (high vs. normal) were identified. Of the 442,474 CpG sites, DNAm at 159 CpGs in males and 212 in females were potentially associated with BMI trajectories. Assessment of their association with asthma incidence identified 9 CpGs in males and 6 CpGs in females. DNAm at 4 of these 15 CpGs showed statistically significant mediation effects (p-value < 0.05). At two of the 4 CpGs (cg23632109 and cg10817500), DNAm completely mediated the association (i.e., only statistically significant indirect effects were identified). In the ALSPAC cohort, at all four CpGs, the same direction of mediating effects were observed as those found in the IoW cohort, although statistically insignificant. Conclusion: The association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm.
ALSPAC, Asthma acquisition, BMI trajectory, DNA methylation, IOWBC
Rathod, Rutu
4d0f6483-9248-4468-8d51-1e0e378b9cc4
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Perunthadambil Kadalayil, Latha
e620b801-844a-45d9-acaf-e0a58acd7cf2
Relton, Caroline L.
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Ring, Susan
79941daa-7ae8-47f1-beb4-e8560ce12fd8
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
23 July 2021
Rathod, Rutu
4d0f6483-9248-4468-8d51-1e0e378b9cc4
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Perunthadambil Kadalayil, Latha
e620b801-844a-45d9-acaf-e0a58acd7cf2
Relton, Caroline L.
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Ring, Susan
79941daa-7ae8-47f1-beb4-e8560ce12fd8
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Rathod, Rutu, Zhang, Hongmei, Karmaus, Wilfried, Ewart, Susan, Perunthadambil Kadalayil, Latha, Relton, Caroline L., Ring, Susan, Arshad, Syed and Holloway, John
(2021)
BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA Methylation.
Allergy, Asthma & Clinical Immunology, 17 (1), [77].
(doi:10.1186/s13223-021-00575-w).
Abstract
Purpose: body mass index (BMI) is associated with asthma but associations of BMI temporal patterns with asthma incidence are unclear. Previous studies suggest that DNA methylation (DNAm) is associated with asthma status and variation in DNAm is a consequence of BMI changes. This study assessed the direct and indirect (via DNAm) effects of BMI trajectories in childhood on asthma incidence at young adulthood.
Methods: data from the Isle of Wight (IoW) birth cohort were included in the analyses. Group-based trajectory modelling was applied to infer latent BMI trajectories from ages 1 to 10 years. An R package, ttscreening, was applied to identify differentially methylated CpGs at age 10 years associated with BMI trajectories, stratified for sex. Logistic regressions were used to further exclude CpGs with DNAm at age 10 years not associated with asthma incidence at 18 years. CpGs discovered via path analyses that mediated the association of BMI trajectories with asthma incidence in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Children and Parents (ALSPAC).
Results: two BMI trajectories (high vs. normal) were identified. Of the 442,474 CpG sites, DNAm at 159 CpGs in males and 212 in females were potentially associated with BMI trajectories. Assessment of their association with asthma incidence identified 9 CpGs in males and 6 CpGs in females. DNAm at 4 of these 15 CpGs showed statistically significant mediation effects (p-value < 0.05). At two of the 4 CpGs (cg23632109 and cg10817500), DNAm completely mediated the association (i.e., only statistically significant indirect effects were identified). In the ALSPAC cohort, at all four CpGs, the same direction of mediating effects were observed as those found in the IoW cohort, although statistically insignificant. Conclusion: The association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm.
Text
Main text file bmi asthma_revised final
- Accepted Manuscript
Text
Figures2
- Accepted Manuscript
Text
Supplemental tables and figures
- Accepted Manuscript
Text
s13223-021-00575-w
- Version of Record
More information
Accepted/In Press date: 2 July 2021
Published date: 23 July 2021
Additional Information:
Funding Information:
The authors are thankful to the nurses and staff at the David Hide Asthma & Allergy Research Centre, Isle of Wight, UK, for their help in recruitment and sample collections, and are thankful to all the IOWBC participants. Our special thanks also go to the High-Performance Computing facility provided by the University of Memphis. For ALSPAC, DNA extraction and generation of Illumina array data was carried out in the Bristol Bioresource Laboratories at the University of Bristol, UK. We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.
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. 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:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
Keywords:
ALSPAC, Asthma acquisition, BMI trajectory, DNA methylation, IOWBC
Identifiers
Local EPrints ID: 452141
URI: http://eprints.soton.ac.uk/id/eprint/452141
ISSN: 1710-1492
PURE UUID: c048a4ad-ab0d-43bc-941e-afa2f1a9449a
Catalogue record
Date deposited: 25 Nov 2021 18:44
Last modified: 17 Mar 2024 02:45
Export record
Altmetrics
Contributors
Author:
Rutu Rathod
Author:
Hongmei Zhang
Author:
Wilfried Karmaus
Author:
Susan Ewart
Author:
Caroline L. Relton
Author:
Susan Ring
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
