Ara h 1 Peptide Immunotherapy Ameliorates Peanut-Induced Anaphylaxis

Abstract

S U N D A Y 515 Identifying CpG Sites Associated with Eczema Via Random Forest Screening of Epigenome-Wide DNA Methylation Bilal M. Quraishi, Hongmei Zhang, PhD, Todd M. Everson, Gabrielle A. Lockett, PhD, Meredith Ray, John W. Holloway, PhD, Syed H. Arshad, DM, FRCP, Wilfried Karmaus, MD, DrMed, MPH; University of Memphis, Memphis, TN, University of South Carolina, Columbia, SC, University of Southampton, Southampton, United Kingdom, University of Southampton, United Kingdom, The David Hide Asthma and Allergy Research Centre, United Kingdom. RATIONALE: The prevalence of eczema among children of industrialized countries is increasing. There is some evidence that DNAmethylation plays a role in eczema, however, there is lack of epi-genome-wide study on their association. METHODS: Association between eczema and DNA methylation was studied in 18year-old subjects (n5366) from the Isle of Wight (IOW) birth Cohort. To efficiently screen cytosine-phospate-guanine (CpG) sites in epi-genome-wide, we applied the approach of random forest (RF) ensemble. A total of 307,357 CpGs were subjected to random forest data reduction, repeatedly dropping 50% of variables with lowest variable importance measures until the misclassification rate showed a significant increase. Functional annotation and pathway analyses along with logistic regressions were performed to further evaluate the selected RF-CpG sites. RESULTS: The RF method yielded 75 CpGs, 72 of which are linked to eczema corroborated by logistic regression. Eczema-associated CpGs, e.g., in genes PARD3 and GUCY1A3, were significantly enriched within the pathways ‘Tight junction’ and ‘Gap junction’ (P values 0.0008 and 0.002 respectively, after correcting for multiple testing with false discovery rate of 0.05). It has been shown that genes in these pathways are correlated to allergic and immune related diseases. CONCLUSIONS: TheRFEnsemblemethodwas successfully utilized for epigenome-wide scanning to identify epigenetic loci associated with eczema, detecting both previously known and novel CpG sites. The significant enrichment of differentially methylated CpGs within tight and gap junction pathway genes implicates epigenetic regulation in epidermal barrier dysfunction in eczema.