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Changes of DNA methylation are associated with changes in lung function during adolescence

Changes of DNA methylation are associated with changes in lung function during adolescence
Changes of DNA methylation are associated with changes in lung function during adolescence
Background
Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs.

Methods
Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped.

Results
For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development.

Conclusions
The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

1465-9921
Sunny, Shadia Khan
a77127e5-1281-445d-b8cb-dd58fab1b63e
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Relton, Caroline L.
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Henderson, A. John
03d06941-3f2c-4a2e-998b-8d18124049d1
Merid, Simon Kebede
97470f65-a3fd-4aaf-8637-e0dea6f1114e
Melén, Erik
c7ee5423-aed5-4905-80b3-65bc07192e0c
Hallberg, Jenny
36773a89-81a0-4d5d-bea3-bfac09831d04
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Holloway, John W.
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Sunny, Shadia Khan
a77127e5-1281-445d-b8cb-dd58fab1b63e
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Relton, Caroline L.
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Henderson, A. John
03d06941-3f2c-4a2e-998b-8d18124049d1
Merid, Simon Kebede
97470f65-a3fd-4aaf-8637-e0dea6f1114e
Melén, Erik
c7ee5423-aed5-4905-80b3-65bc07192e0c
Hallberg, Jenny
36773a89-81a0-4d5d-bea3-bfac09831d04
Arshad, S. Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a

Sunny, Shadia Khan, Zhang, Hongmei, Rezwan, Faisal I., Relton, Caroline L., Henderson, A. John, Merid, Simon Kebede, Melén, Erik, Hallberg, Jenny, Arshad, S. Hasan, Ewart, Susan and Holloway, John W. (2020) Changes of DNA methylation are associated with changes in lung function during adolescence. Respiratory Research, 21 (1), [80]. (doi:10.1186/s12931-020-01342-y).

Record type: Article

Abstract

Background
Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs.

Methods
Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped.

Results
For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development.

Conclusions
The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

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More information

Accepted/In Press date: 25 March 2020
e-pub ahead of print date: 7 April 2020

Identifiers

Local EPrints ID: 446632
URI: http://eprints.soton.ac.uk/id/eprint/446632
ISSN: 1465-9921
PURE UUID: 68e2ab30-719e-4040-a614-fe8ccf44e14d
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 16 Feb 2021 17:35
Last modified: 15 Sep 2021 02:00

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Contributors

Author: Shadia Khan Sunny
Author: Hongmei Zhang
Author: Faisal I. Rezwan ORCID iD
Author: Caroline L. Relton
Author: A. John Henderson
Author: Simon Kebede Merid
Author: Erik Melén
Author: Jenny Hallberg
Author: S. Hasan Arshad
Author: Susan Ewart

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