Emma E. Thompson, Xiaoyuan Zhong, Peter Carbonetto et al. doi: https://doi.org/10.1101/2024.10.03.24314618
Abstract
Background
Asthma is the most common chronic respiratory disease in children, but little is known about genetic contributions to its underlying endotypes. To address this gap, we studied the methylome, transcriptome, and genome from children with extensive phenotyping from birth.
Methods We performed DNA methylation (DNAm) studies using the Asthma&Allergy array and RNA-sequencing in nasal mucosal cells from 284 children (age 11 years) in the Urban Environment and Childhood Asthma (URECA) birth cohort with genotypes from whole-genome sequencing. Using empirical Bayes matrix factorization on all CpGs on the array, we derived 16 DNAm signatures and tested for associations between phenotypes and gene expression. We then replicated results in two additional cohorts and estimated the heritability of phenotype-associated signatures using single-nucleotide polymorphisms (SNPs) associated with an allergic disease, and with CpGs and genes associated with the signatures.
|
Overlap and number of CpGs and genes associated with DNAm signatures 5, 8, and 16. |