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

Allergy Asthma Clin Immunol 2019 24;15:43. Epub 2019 Jul 24.

3Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, 236A Robison Hall, Memphis, TN 38152 USA.

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 displayed particularly strong associations after cellular heterogeneity adjustments in both cohorts (OR = 0.17, 95% CI 0.04-0.57) (OR = 0.57, 95% CI 0.38-0.87). Additionally, higher expression of (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 , which may serve as markers of, predictors of, and potentially etiologic factors involved in asthma and early life wheeze.

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https://aacijournal.biomedcentral.com/articles/10.1186/s1322
Publisher Site
http://dx.doi.org/10.1186/s13223-019-0356-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657035PMC
July 2019
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References

(Supplied by CrossRef)

FD Martinez et al.
Lancet. 2013

J Lötvall et al.
J Allergy Clin Immunol. 2011

A DeVries et al.
Curr Opin Allergy Clin Immunol 2015

AL Durham et al.
Biochim Biophys Acta 2011

PA Jones et al.
Nat Rev Genet 2012

S Ho et al.
J Allergy Clin Immunol 2010

IV Yang et al.
Am J Respir Crit Care Med 2012

IV Yang et al.
J Allergy Clin Immunol 2015

R Arathimos et al.
Clin Epigenetics. 2017

SJ Barton et al.
Clin Exp Allergy 2017

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