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

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.