The impact of the cord blood methylome on early-onset atopic dermatitis

Document Type

Conference Proceeding

Publication Date

2-1-2025

Publication Title

J Allergy Clin Immunol

Abstract

Rationale: Atopic dermatitis (AD) affects 30% of children worldwide, contributing to significant health and social burdens, particularly those with early-onset disease. DNA methylation (DNAm) is associated with AD, but little is known of its role at birth in predicting early-onset AD. We aimed to characterize cord-blood DNAm in those with and without early-onset AD by age 2 years. Methods: The custom Asthma&Allergy array was applied to 302 cord DNA samples in the Wayne County, Health, Environment, Allergy, and Asthma Longitudinal Study(WHEALS). A single-site epigenome wide association study(EWAS) was performed to identify CpG sites associated with early-onset AD(q-value < 0.01). Combp was used to identify differentially methylated regions(DMR) within 1 kb range (false discovery rate(FDR) < 0.001). An early-onset AD poly-CpG score was created by performing CpG site feature selection (p < 0.01) using an elastic net penalized logistic regression model for CpG sites associated with early-onset AD. Results: There were 75 early-onset AD cases and 227 no-AD controls. 16 DMRs (FDR adjusted p-value < 0.001) were significantly associated with early-onset AD. Pathway analyses identified enrichment for T-cell receptor signaling, MHC class II antigen presentation, and IFNg signaling pathways. For our poly-CpG score, 1,275 met the nominal feature selection p-value < 0.01, with 180 CpG sites in the final model. Our poly-CpG score was highly predictive of early-onset AD with an area under the receiver operator characteristic curve of 93.7% (sensitivity=84.9%, specificity=86.3%). Conclusions: Differential cord-blood DNAm is associated with risk of early-onset AD by age 2. Future studies would include larger, diverse cohorts to assess the validity of our findings.

Volume

155

Issue

2

First Page

AB433

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