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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | Allergy, Asthma & Clinical Immunology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13223-019-0356-z |
| _version_ | 1818296078834860032 |
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| author | Todd M. Everson Hongmei Zhang Gabrielle A. Lockett Akhilesh Kaushal Melinda Forthofer Susan L. Ewart Kimberley Burrows Caroline L. Relton Gemma C. Sharp A. John Henderson Veeresh K. Patil Faisal I. Rezwan S. Hasan Arshad John W. Holloway Wilfried Karmaus |
| author_facet | Todd M. Everson Hongmei Zhang Gabrielle A. Lockett Akhilesh Kaushal Melinda Forthofer Susan L. Ewart Kimberley Burrows Caroline L. Relton Gemma C. Sharp A. John Henderson Veeresh K. Patil Faisal I. Rezwan S. Hasan Arshad John W. Holloway Wilfried Karmaus |
| author_sort | Todd M. Everson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T03:57:49Z |
| format | Article |
| id | doaj.art-cb8fd19935404f6c9593db29191ef4bb |
| institution | Directory Open Access Journal |
| issn | 1710-1492 |
| language | English |
| last_indexed | 2024-12-13T03:57:49Z |
| publishDate | 2019-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Allergy, Asthma & Clinical Immunology |
| spelling | doaj.art-cb8fd19935404f6c9593db29191ef4bb2022-12-22T00:00:35ZengBMCAllergy, Asthma & Clinical Immunology1710-14922019-07-0115111210.1186/s13223-019-0356-zEpigenome-wide association study of asthma and wheeze characterizes loci within HK1Todd M. Everson0Hongmei Zhang1Gabrielle A. Lockett2Akhilesh Kaushal3Melinda Forthofer4Susan L. Ewart5Kimberley Burrows6Caroline L. Relton7Gemma C. Sharp8A. John Henderson9Veeresh K. Patil10Faisal I. Rezwan11S. Hasan Arshad12John W. Holloway13Wilfried Karmaus14Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South CarolinaDivision of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of MemphisHuman Development and Health, Faculty of Medicine, University of Southampton, Southampton General HospitalCenter for Precision and Environmental Health, Baylor College of MedicineDepartment of Epidemiology and Biostatistics, Arnold School of Public Health, University of South CarolinaDepartment of Large Animal Clinical Sciences, Michigan State UniversityMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of BristolMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of BristolMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of BristolAvon Longitudinal Study of Parents and Children, Population Health Sciences, Bristol Medical School, University of BristolThe David Hide Asthma and Allergy Research Centre, St Mary’s HospitalHuman Development and Health, Faculty of Medicine, University of Southampton, Southampton General HospitalClinical and Experimental Sciences Faculty of Medicine, University of Southampton, Southampton General HospitalHuman Development and Health, Faculty of Medicine, University of Southampton, Southampton General HospitalDivision of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of MemphisAbstract 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.http://link.springer.com/article/10.1186/s13223-019-0356-zALSPACARIESAsthmaExpressionHexokinase-1HK1 |
| spellingShingle | Todd M. Everson Hongmei Zhang Gabrielle A. Lockett Akhilesh Kaushal Melinda Forthofer Susan L. Ewart Kimberley Burrows Caroline L. Relton Gemma C. Sharp A. John Henderson Veeresh K. Patil Faisal I. Rezwan S. Hasan Arshad John W. Holloway Wilfried Karmaus Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 Allergy, Asthma & Clinical Immunology ALSPAC ARIES Asthma Expression Hexokinase-1 HK1 |
| title | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
| title_full | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
| title_fullStr | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
| title_full_unstemmed | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
| title_short | Epigenome-wide association study of asthma and wheeze characterizes loci within HK1 |
| title_sort | epigenome wide association study of asthma and wheeze characterizes loci within hk1 |
| topic | ALSPAC ARIES Asthma Expression Hexokinase-1 HK1 |
| url | http://link.springer.com/article/10.1186/s13223-019-0356-z |
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