EQTM (expression quantitative trait methylation) analyses uncover associations between DNA methylation markers and gene expression. Most eQTM analyses of complex diseases have focused on cis-eQTM pairs (within 1 Mb).
To identify cis- and trans- methylation markers associated with gene expression in airway epithelium from youth with and without atopic asthma.
We conducted both cis- and trans-eQTM analyses in nasal (airway) epithelial samples from 158 Puerto Rican youth with atopic asthma and 100 control subjects without atopy or asthma. We then attempted to replicate our findings in nasal epithelial samples from two studies of children, while also examining whether our results in nasal epithelium overlap with those from an eQTM analysis in white blood cells from the Puerto Rican subjects.
We identified 9,108 cis-eQTM pairs and 2,131,500 trans-eQTM pairs. Trans-associations were significantly enriched for transcription factor- and miRNA-target genes. Further, significant CpGs were differentially methylated in atopic asthma and significant genes were enriched for genes differentially expressed in atopic asthma. 50.7% to 62.6% of cis- and trans-eQTM pairs identified in Puerto Rican youth were replicated in two smaller cohorts at FDR-P <0.1. Replicated genes in the trans-eQTM analysis included biologically plausible asthma-susceptibility genes (e.g., HDC, NLRP3, ITGAE, CDH26, and CST1) and are enriched in immune pathways.
Studying both cis- and trans-epigenetic regulation of airway epithelial gene expression can identify potential causal and regulatory pathways or networks for childhood asthma. Trans-eQTM CpGs may regulate gene expression in airway epithelium through effects on transcription factor- and miRNA-target genes.
Copyright © 2023. Published by Elsevier Inc.
