Epigenome‐Wide Association Study of Asthma Exacerbations in Europeans

• DOI: 10.1111/all.16490
• Publication Date: 2025-02-05T11:45:08Z
• Authors: Elena Martin‐Gonz...; Javier Perez‐Garcia; Esther Herrera‐Luis; Mario Martin‐Almeida; Simon Kebede‐Merid; Natalia Hernandez...; Fabian Lorenzo‐Diaz; Ruperto González‐...; Olaia Sardón; José M. Hernández...; Paloma Poza‐Guedes; Inmaculada Sánche...; Elena Mederos‐Luis; Paula Corcuera; Leyre López‐Ferná...; Berta Román‐Bernal; Antoaneta A. Tonc...; Susanne Harner; Christine Wolff; Susanne Brandstetter; Mahmoud Ibrahim A...; Simone Hashimoto; Susanne J. H. Vij...; Aletta D. Kraneveld; Uroš Potočnik; Michael Kabesch; Anke H. Maitland‐...; Jesús Villar; Erik Melén; Maria Pino‐Yanes
• Keywords: dNaM; Epigenome; Genome-wide Association Study; CpG site; Genetic Association

ABSTRACT Background Asthma exacerbations (AEs) represent the major contributor to global asthma burden. Although genetic and environmental factors have been associated with AEs, role of epigenetics remains uncovered. Objective This study aimed identify whole blood DNA methylation (DNAm) markers AEs in Europeans. Methods DNAm was assessed 406 samples from Spanish individuals using Infinium MethylationEPIC microarray (Illumina). An epigenome‐wide association conducted test at differentially methylated positions, regions, epigenetic modules. CpGs suggestively (false discovery rate [FDR] < 0.1) were followed up for replication 222 European individuals, genome‐wide significance ( p 9 × 10 −8 ) declared after meta‐analyzing samples. Additional assessment performed nasal tissue data 155 individuals. The effects variation on through cis‐methylation quantitative trait loci (meQTL) analysis. Enrichment analyses previous EWAS signals conducted. Results Four two replicated reached genomic meta‐analysis (annotated ZBTB16 BAIAP2 ). Of those, CpG cg25345365 cross‐tissue validated epithelium = 0.003) five independent meQTLs (FDR 0.05). Additionally, four regions one module significantly AEs. revealed an overrepresentation prior associations prenatal exposures, immune‐mediated diseases, mortality. Conclusions may contribute Europeans, capturing risk factors.