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

Research output: Contribution to journalArticle

Original languageEnglish
Article number43 (2019)
Number of pages12
JournalAllergy, Asthma and Clinical Immunology
Volume15
DOIs
DateAccepted/In press - 12 Jul 2019
DatePublished (current) - 24 Jul 2019

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 (OR-IOW = 0.17, 95% CI = 0.04-0.57) (OR-ALSPAC = 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.

    Research areas

  • methylation, Isle of Wight, infant wheeze, HK1, hexokinase-1, expression, asthma, ARIES, ALSPAC

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  • Full-text PDF (final published version)

    Rights statement: This is the final published version of the article (version of record). It first appeared online via Springer Nature at https://aacijournal.biomedcentral.com/articles/10.1186/s13223-019-0356-z#article-info. Please refer to any applicable terms of use of the publisher.

    Final published version, 1023 KB, PDF document

    Licence: CC BY

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