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

Todd M Everson, Hongmei Zhang, Gabrielle A Lockett, Akhilesh Kaushal, Melinda Forthofer, Susan Ewart, Kimberley Burrows, Caroline Relton, Gemma Sharp, John Henderson, Veeresh Patil, Faisal I Rezwan, Hasan Arshad, John W Holloway, Wilfried Karmaus

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)
68 Downloads (Pure)

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.
Original languageEnglish
Article number43 (2019)
Number of pages12
JournalAllergy, Asthma and Clinical Immunology
Volume15
DOIs
Publication statusPublished - 24 Jul 2019

Keywords

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

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