المؤلفون: Manuel E. Soto-Quiros, Donglei Hu, Soyeon Kim, Yueh-Ying Han, Edna Acosta-Pérez, Esther Herrera-Luis, Celeste Eng, Raimon Rios, Mauricio Lima Barreto, Esteban G. Burchard, Nadia Boutaoui, Sam S. Oh, Qi Yan, Cancan Qi, Juan C. Celedón, Scott T. Weiss, Lydiana Avila, Gerard H. Koppelman, Cheng-Jian Xu, Jessica Lasky-Su, Megan R. Kiedrowski, Jennifer M. Bomberger, Wei Chen, Maria Pino-Yanes, Glorisa Canino, Scott Huntsman, Camila Alexandrina Figueiredo, Erick Forno, Michelle M. Cloutier, Rong Zhang

المساهمون: Groningen Research Institute for Asthma and COPD (GRIAC)

المصدر: European Respiratory Journal, 57, 4
European Respiratory Journal, 57(4):2002693. EUROPEAN RESPIRATORY SOC JOURNALS LTD
Eur Respir J
European Respiratory Journal, 57

مصطلحات موضوعية: 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Genome-wide association study, Locus (genetics), Single-nucleotide polymorphism, Quantitative trait locus, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Internal medicine, medicine, Humans, SNP, Child, Asthma, business.industry, Puerto Rico, Hispanic or Latino, medicine.disease, 030104 developmental biology, 030228 respiratory system, Expression quantitative trait loci, DNA methylation, business, Brazil, Genome-Wide Association Study

الوصف: Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups.To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative trait methylation analyses to assess whether the top single nucleotide polymorphism (SNP) in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents.In the meta-analysis of GWAS, an SNP inFLJ22447(rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbation (95% CI 1.34–1.79, p=6.3×10−9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at theFLJ22447locus, which was in turn associated with increased expression ofKCNJ2-AS1in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10−7).SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG inFLJ22447and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (KCNJ2-AS1).

وصف الملف: application/pdf

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5627d794727674f8bdbf5ebceeda19d6
https://doi.org/10.1183/13993003.02693-2020