Newborn blood DNA methylation and childhood asthma: findings from the ECHO program.

Abstract

Background: DNA methylation (DNAm) at birth has been linked to childhood asthma in epigenome-wide association studies (EWASs). However, existing EWASs have limited representation of non-European and extremely preterm participants and have not explored sex-specific DNAm differences. This study examined the association between DNAm in newborn blood and subsequent childhood asthma risk in a diverse population.

Methods: Data from the Environmental influences on Child Health Outcomes (ECHO) Program were used for EWAS meta-analyses in United States (US) cohorts of children born before and after 28 weeks of gestation. DNAm was measured in newborn blood using Illumina arrays. Childhood asthma was defined as provider-diagnosed asthma with persistent symptoms beyond age 5. Linear regression was used to identify differentially methylated positions (DMPs), and "comb-p" was used to identify differentially methylated regions (DMRs). Sex-stratified analyses were performed.

Results: The meta-analysis included 942 children (369 asthma cases) born after 28 weeks of gestation. We identified a novel DMP (cg24749470 in CADM1, P = 9.31 × 10-8) and 18 DMRs (Šidák P-value <.001) associated with asthma, with four DMRs in the human leukocyte antigen region. At these four DMRs, the association between DNAm and asthma differed by sex. In the extremely preterm cohort (n = 271, 106 asthma cases), we identified 20 DMRs, with two novel asthma-associated DMPs (cg03237868 in SPATA18, P = 2.71 × 10-8; cg20681219 in IRF2, P = 5.18 × 10-8) identified in males.

Conclusion: In US children born before and after 28 weeks of gestation, we discovered novel genomic loci linking newborn blood DNAm to childhood asthma, suggesting DNAm involvement in early asthma development.