Dataset Information

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

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.

SUBMITTER: Everson TM

PROVIDER: S-EPMC6657035 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Epigenome-wide association study of asthma and wheeze characterizes loci within <i>HK1</i>.

Everson Todd M TM Zhang Hongmei H Lockett Gabrielle A GA Kaushal Akhilesh A Forthofer Melinda M Ewart Susan L SL Burrows Kimberley K Relton Caroline L CL Sharp Gemma C GC Henderson A John AJ Patil Veeresh K VK Rezwan Faisal I FI Arshad S Hasan SH Holloway John W JW Karmaus Wilfried W

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 20190724

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 31367216

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Project description:IntroductionDNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association study (EWAS) of lung function has been performed in this population. Here, we aimed to identify DNA methylation patterns associated with lung function in pediatric asthma among Latinos.ResultsWe conducted an EWAS in whole blood from 250 Puerto Rican and 148 Mexican American children and young adults with asthma. A total of five CpGs exceeded the genome-wide significance threshold of p = 1.17 × 10-7 in the combined analyses from Puerto Ricans and Mexican Americans: cg06035600 (MAP3K6, p = 6.13 × 10-8) showed significant association with pre-bronchodilator Tiffeneau-Pinelli index, the probes cg00914963 (TBC1D16, p = 1.04 × 10-7), cg16405908 (MRGPRE, p = 2.05 × 10-8), and cg07428101 (MUC2, p = 5.02 × 10-9) were associated with post-bronchodilator forced vital capacity (FVC), and cg20515679 (KCNJ6) with post-bronchodilator Tiffeneau-Pinelli index (p = 1.13 × 10-8). However, these markers did not show significant associations in publicly available data from Europeans (p > 0.05). A methylation quantitative trait loci analysis revealed that methylation levels at these CpG sites were regulated by genetic variation in Latinos and the Biobank-based Integrative Omics Studies (BIOS) consortium. Additionally, two differentially methylated regions in REXOC and AURKC were associated with pre-bronchodilator Tiffeneau-Pinelli index (adjusted p < 0.05) in Puerto Ricans and Mexican Americans. Moreover, we replicated some of the previous differentially methylated signals associated with lung function in non-Latino populations.ConclusionsWe replicated previous associations of epigenetic markers with lung function in whole blood and identified novel population-specific associations shared among Latino subgroups.