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

Allergy, Asthma & Clinical Immunology

A. John Henderson¹  Akhilesh Kaushal²  S. Hasan Arshad³  Melinda Forthofer⁴  Todd M. Everson⁴  Susan L. Ewart⁵  Wilfried Karmaus⁶  Hongmei Zhang⁶  John W. Holloway⁷  Faisal I. Rezwan⁷  Gabrielle A. Lockett⁷  Caroline L. Relton⁸  Gemma C. Sharp⁸  Kimberley Burrows⁸  Veeresh K. Patil⁹ 

[1] Avon Longitudinal Study of Parents and Children, Population Health Sciences, Bristol Medical School, University of Bristol;Center for Precision and Environmental Health, Baylor College of Medicine;Clinical and Experimental Sciences Faculty of Medicine, University of Southampton, Southampton General Hospital;Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina;Department of Large Animal Clinical Sciences, Michigan State University;Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis;Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital;MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol;The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital;

关键词: ALSPAC;    ARIES;    Asthma;    Expression;    Hexokinase-1;    HK1;   

DOI  :  10.1186/s13223-019-0356-z

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown