Epigenome-Wide Association Study of Asthma Exacerbations in Europeans.

IF 12.6 1区医学 Q1 ALLERGY

Allergy Pub Date : 2025-02-05 DOI:10.1111/all.16490

Elena Martin-Gonzalez, Javier Perez-Garcia, Esther Herrera-Luis, Mario Martin-Almeida, Simon Kebede-Merid, Natalia Hernandez-Pacheco, Fabian Lorenzo-Diaz, Ruperto González-Pérez, Olaia Sardón, José M Hernández-Pérez, Paloma Poza-Guedes, Inmaculada Sánchez-Machín, Elena Mederos-Luis, Paula Corcuera, Leyre López-Fernández, Berta Román-Bernal, Antoaneta A Toncheva, Susanne Harner, Christine Wolff, Susanne Brandstetter, Mahmoud Ibrahim Abdel-Aziz, Simone Hashimoto, Susanne J H Vijverberg, Aletta D Kraneveld, Uroš Potočnik, Michael Kabesch, Anke H Maitland-van der Zee, Jesús Villar, Erik Melén, Maria Pino-Yanes

{"title":"Epigenome-Wide Association Study of Asthma Exacerbations in Europeans.","authors":"Elena Martin-Gonzalez, Javier Perez-Garcia, Esther Herrera-Luis, Mario Martin-Almeida, Simon Kebede-Merid, Natalia Hernandez-Pacheco, Fabian Lorenzo-Diaz, Ruperto González-Pérez, Olaia Sardón, José M Hernández-Pérez, Paloma Poza-Guedes, Inmaculada Sánchez-Machín, Elena Mederos-Luis, Paula Corcuera, Leyre López-Fernández, Berta Román-Bernal, Antoaneta A Toncheva, Susanne Harner, Christine Wolff, Susanne Brandstetter, Mahmoud Ibrahim Abdel-Aziz, Simone Hashimoto, Susanne J H Vijverberg, Aletta D Kraneveld, Uroš Potočnik, Michael Kabesch, Anke H Maitland-van der Zee, Jesús Villar, Erik Melén, Maria Pino-Yanes","doi":"10.1111/all.16490","DOIUrl":null,"url":null,"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 × 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.","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6000,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Allergy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/all.16490","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}

引用次数: 0

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 × 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.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Allergy 医学-过敏

CiteScore

26.10

自引率

9.70%

发文量

393

审稿时长

2 months

期刊介绍： Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.