Epigenome-wide association study of asthma in the Canary Islands

<bold>Background:</bold> The Canary Islands have a high asthma prevalence due to specific environmental factors, such as Saharan dust, high environmental humidity, and the presence of dust mites, as well as their unique genetic composition, both European and North African. DNA methylation (DNAm) reflects the interaction between environmental and genetic factors. <bold>Aim:</bold> To investigate DNAm markers associated with asthma in the Canarian population and validate these findings in high-risk asthma populations. <bold>Methods:</bold> DNAm was measured in blood samples from 689 Canarian individuals (GEMAS study) using the EPIC array (Illumina). EWAS of asthma was performed adjusting for age, sex, ancestry, and cellular heterogeneity. Genome-wide significance was declared at <italic>p</italic><9x10^-8. Differentially methylated regions (DMRs) and enrichment analysis were performed. Multiple comparisons were adjusted using a false discovery rate (FDR)<0.05. Replication was evaluated in 1,015 Latinos and 756 African Americans. <bold>Results:</bold> 67 CpGs and 36 DMRs were associated with asthma (FDR<0.05). The CpGs cg19764973 (<italic>STX3</italic>) and cg27245539 (<italic>GYPC</italic>) surpassed the genome-wide significant threshold. Most genes where these CpGs are located have been associated with asthma and related phenotypes. Enrichment analysis revealed associations with asthma phenotypes, IL-5 production, and birth weight. Two CpGs replicated in Latinos, with one also replicating in African Americans. <bold>Conclusions:</bold> This study, the first EWAS of asthma in the Canary Islands population, revealed novel DNA markers of asthma susceptibility, some of which are shared with other high-risk asthma populations. <bold>Funding:</bold> MICIU/AEI/10.13039/501100011033 (PID2020-116274RB-I00), PIFIISC22/24, FPU23/02667, FPI2024010123.