The following is a summary of “A functional genomics pipeline to identify high-value asthma and allergy CpGs in the human methylome,” published in the JUNE 2023 issue of Allergy & Immunology by Morin, et al.
DNA methylation is an essential epigenetic modification at cytosine-phosphate-guanine (CpG) dinucleotides. However, genome-wide variation in DNA methylation has yet to be studied due to limitations in commercial high-throughput arrays that only cover a limited number of variable CpGs. For a study, researchers sought to explore the hidden portion of the epigenome by combining whole-genome bisulfite sequencing with in silico evidence of gene regulatory regions to design a custom array targeting high-value CpGs. The focus was on airway epithelial cells from children with and without allergic asthma, as these cells play a crucial role in mediating the effects of inhaled substances on asthma and allergic disease risk.
Differentially methylated regions were identified using whole-genome bisulfite sequencing of nasal epithelial cell DNA from 39 children of European and African ancestries with and without allergic asthma. CpGs from these regions and previous epigenome-wide association studies (EWAS) of allergy or asthma and genome-wide association study loci were selected and overlapped with functional annotations to create a custom Asthma & Allergy array. Both the custom array and the EPIC array were used to perform EWAS of allergic sensitization (AS) in nasal epithelial cell DNA from children in the URECA (Urban Environment and Childhood Asthma) and INSPIRE [Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure] birth cohorts. Each CpG on the arrays was associated with its nearest gene, and its promotor capture Hi-C interacting gene, and expression quantitative trait methylation (eQTM) studies were conducted for both sets of genes.
The custom array CpGs showed enrichment for intermediate methylation levels compared to the EPIC array CpGs. Intermediate methylation CpGs were also enriched among those associated with AS and for eQTMs on both arrays.
The study identified signature features of high-value CpGs. It provided evidence for epigenetic regulation of genes at AS EWAS loci consistent across different races/ethnicities, age groups, and geographical locations.
Source: jacionline.org/article/S0091-6749(23)00149-5/fulltext