Martin-Gonzalez, Elena and Perez-Garcia, Javier and Herrera-Luis, Esther and Martin-Almeida, Mario and Kebede-Merid, Simon and Hernandez-Pacheco, Natalia and Lorenzo-Diaz, Fabian and Gonzalez-Perez, Ruperto and Sardon, Olaia and Hernandez-Perez, Jose M. and Poza-Guedes, Paloma and Sanchez-Machin, Inmaculada and Mederos-Luis, Elena and Corcuera, Paula and Lopez-Fernandez, Leyre and Roman-Bernal, Berta and Toncheva, Antoaneta A. and Harner, Susanne and Wolff, Christine and Brandstetter, Susanne and Abdel-Aziz, Mahmoud Ibrahim and Hashimoto, Simone and Vijverberg, Susanne J. H. and Kraneveld, Aletta D. and Potocnik, Uros and Kabesch, Michael and Maitland-van der Zee, Anke H. and Villar, Jesus and Melen, Erik and Pino-Yanes, Maria (2025) Epigenome-Wide Association Study of Asthma Exacerbations in Europeans. ALLERGY, 80 (4). pp. 1086-1099. ISSN 0105-4538, 1398-9995
Full text not available from this repository. (Request a copy)Abstract
Background Asthma exacerbations (AEs) represent the major contributor to the global asthma burden. Although genetic and environmental factors have been associated with AEs, the role of epigenetics remains uncovered. Objective This study aimed to identify whole blood DNA methylation (DNAm) markers associated with AEs in Europeans. Methods DNAm was assessed in 406 blood samples from Spanish individuals using the Infinium MethylationEPIC microarray (Illumina). An epigenome-wide association study was conducted to test the association of DNAm with AEs at differentially methylated positions, regions, and epigenetic modules. CpGs suggestively associated with AEs (false discovery rate [FDR] < 0.1) were followed up for replication in 222 European individuals, and the genome-wide significance (p < 9 x 10-8) was declared after meta-analyzing the discovery and replication samples. Additional assessment was performed using nasal tissue DNAm data from 155 Spanish individuals. The effects of genetic variation on DNAm were assessed through cis-methylation quantitative trait loci (meQTL) analysis. Enrichment analyses of previous EWAS signals were conducted. Results Four CpGs were associated with AEs, and two were replicated and reached genomic significance in the meta-analysis (annotated to ZBTB16 and BAIAP2). Of those, CpG cg25345365 (ZBTB16) was cross-tissue validated in nasal epithelium (p= 0.003) and associated with five independent meQTLs (FDR < 0.05). Additionally, four differentially methylated regions and one module were significantly associated with AEs. Enrichment analyses revealed an overrepresentation of prior epigenetic associations with prenatal and environmental exposures, immune-mediated diseases, and mortality. Conclusions DNAm in whole blood and nasal samples may contribute to AEs in Europeans, capturing genetic and environmental risk factors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DNA METHYLATION; RISK; Asthma; epigenome-wide association study; epigenomics; Europeans; exacerbations |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Jun 2026 12:40 |
| Last Modified: | 02 Jun 2026 12:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67375 |
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