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

Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology
Todd M EversonWilfried Karmaus

Abstract

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. 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. 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). 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 potenti...Continue Reading

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Citations

Jul 9, 2020·International Journal of Epidemiology·S Hasan ArshadWilfried J Karmaus
Sep 10, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Hanna DanielewiczAndrzej Boznański
Mar 31, 2021·Clinical Epigenetics·Mojgan SheikhpourVahid Amiri

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Software Mentioned

Agilent GeneSpring
Ensembl
randomForest
ALSPAC
R

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