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Epigenome-wide association study of asthma- and wheeze characterizes loci within HK1

Epigenome-wide association study of asthma- and wheeze characterizes loci within HK1
Epigenome-wide association study of asthma- and wheeze characterizes loci within HK1
Background:
To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood.

Methods:
We performed epigenome-wide screening with recursive random forest feature selection and internal validation in the IOW birth cohort. We then tested whether we could replicate these findings in the independent cohort ALSPAC and followed-up our top finding with children of the IOW cohort.

Results:
We identified 10 CpG sites associated with adolescent asthma at a 5% false discovery rate (IOW, n = 370), five of which exhibited evidence of associations in the replication study (ALSPAC, n = 720). One site, cg16658191, within HK1 displayed particularly strong associations after cellular heterogeneity adjustments in both cohorts (ORIOW = 0.17, 95% CI 0.04–0.57) (ORALSPAC = 0.57, 95% CI 0.38–0.87). Additionally, higher expression of HK1 (OR = 3.81, 95% CI 1.41–11.77) in cord blood was predictive of wheezing in infancy (n = 82).

Conclusion:
We identified novel associations between asthma and wheeze with methylation at cg16658191 and the expression of HK1, which may serve as markers of, predictors of, and potentially etiologic factors involved in asthma and early life wheeze.
1710-1492
Everson, Todd M.
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Zhang, Hongmei
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Lockett, Gabrielle A.
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Kaushal, Akhilesh
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Forthofer, Melinda
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Ewart, Susan L.
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Burrows, Kimberley
3ad59faa-852a-4936-a512-0843073f8212
Relton, Caroline L.
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Sharp, Gemma C.
1ca7cdb0-ff2c-4679-b625-d00e347fd140
Henderson, A. John
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Patil, Veeresh K.
ca29bab3-2a4d-49e0-8f15-9f2109ecdd64
Rezwan, Faisal I.
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Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John
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Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Everson, Todd M.
0639cdab-214c-4fd3-8181-bfca14ad58ef
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Kaushal, Akhilesh
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Forthofer, Melinda
d0ee39ed-eadd-4f7c-8cf0-07e3bdeeeb7b
Ewart, Susan L.
48158071-d7b8-46b5-8aef-26ffb37eec3b
Burrows, Kimberley
3ad59faa-852a-4936-a512-0843073f8212
Relton, Caroline L.
7a9fe7f7-d14b-4bb7-be71-a3afa6ff8538
Sharp, Gemma C.
1ca7cdb0-ff2c-4679-b625-d00e347fd140
Henderson, A. John
037b2c75-1389-443f-9cdd-c8082f56c3f5
Patil, Veeresh K.
ca29bab3-2a4d-49e0-8f15-9f2109ecdd64
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Holloway, John
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Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853

Everson, Todd M., Zhang, Hongmei, Lockett, Gabrielle A., Kaushal, Akhilesh, Forthofer, Melinda, Ewart, Susan L., Burrows, Kimberley, Relton, Caroline L., Sharp, Gemma C., Henderson, A. John, Patil, Veeresh K., Rezwan, Faisal I., Arshad, Syed, Holloway, John and Karmaus, Wilfried (2019) Epigenome-wide association study of asthma- and wheeze characterizes loci within HK1. Allergy, Asthma & Clinical Immunology, 15, [43]. (doi:10.1186/s13223-019-0356-z).

Record type: Article

Abstract

Background:
To identify novel epigenetic markers of adolescent asthma and replicate findings in an independent cohort, then explore whether such markers are detectable at birth, predictive of early-life wheeze, and associated with gene expression in cord blood.

Methods:
We performed epigenome-wide screening with recursive random forest feature selection and internal validation in the IOW birth cohort. We then tested whether we could replicate these findings in the independent cohort ALSPAC and followed-up our top finding with children of the IOW cohort.

Results:
We identified 10 CpG sites associated with adolescent asthma at a 5% false discovery rate (IOW, n = 370), five of which exhibited evidence of associations in the replication study (ALSPAC, n = 720). One site, cg16658191, within HK1 displayed particularly strong associations after cellular heterogeneity adjustments in both cohorts (ORIOW = 0.17, 95% CI 0.04–0.57) (ORALSPAC = 0.57, 95% CI 0.38–0.87). Additionally, higher expression of HK1 (OR = 3.81, 95% CI 1.41–11.77) in cord blood was predictive of wheezing in infancy (n = 82).

Conclusion:
We identified novel associations between asthma and wheeze with methylation at cg16658191 and the expression of HK1, which may serve as markers of, predictors of, and potentially etiologic factors involved in asthma and early life wheeze.

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Accepted/In Press date: 11 July 2019
Published date: 24 July 2019

Identifiers

Local EPrints ID: 433167
URI: http://eprints.soton.ac.uk/id/eprint/433167
ISSN: 1710-1492
PURE UUID: 7502f7e2-f380-4f7c-937f-86164f213867
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 09 Aug 2019 16:30
Last modified: 18 Feb 2021 16:49

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Contributors

Author: Todd M. Everson
Author: Hongmei Zhang
Author: Gabrielle A. Lockett
Author: Akhilesh Kaushal
Author: Melinda Forthofer
Author: Susan L. Ewart
Author: Kimberley Burrows
Author: Caroline L. Relton
Author: Gemma C. Sharp
Author: A. John Henderson
Author: Veeresh K. Patil
Author: Syed Arshad
Author: John Holloway ORCID iD
Author: Wilfried Karmaus

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