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

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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.

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欧洲人哮喘加重的全表观基因组关联研究

背景：哮喘加重（ae）是全球哮喘负担的主要贡献者。虽然遗传和环境因素与ae有关，但表观遗传学的作用仍未发现。目的：本研究旨在鉴定欧洲人与ae相关的全血DNA甲基化（DNAm）标记。方法：使用Infinium MethylationEPIC微阵列（Illumina）对406份西班牙人的血液样本进行DNAm评估。进行了一项全表观基因组关联研究，以测试dna与ae在不同甲基化位置、区域和表观遗传模块上的关联。在对发现和复制样本进行荟萃分析后，我们宣布CpGs与ae（错误发现率[FDR] -8）呈正相关。使用155名西班牙人的鼻腔组织dna数据进行了额外的评估。通过顺式甲基化数量性状位点（meQTL）分析，评估遗传变异对dna的影响。对之前的EWAS信号进行富集分析。结果：4个CpGs与ae相关，其中2个在meta分析中被复制并达到基因组意义（注释为ZBTB16和BAIAP2）。其中，CpG cg25345365 （ZBTB16）在鼻上皮中被跨组织验证（p= 0.003），并与5个独立的meqtl相关(FDR结论：全血和鼻样本中的DNAm可能与欧洲人的ae有关，捕获遗传和环境风险因素。

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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.