A genome-wide association study of severe asthma exacerbations in Latino children and adolescents

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)
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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 (mQTL), expression quantitative trait locus (eQTL), and expression quantitative trait methylation (eQTM) analyses to assess whether the top 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, a SNP in FLJ22447 (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbations (95% confidence interval=1.34 to 1.79, p=6.3×10-9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the FLJ22447 locus, which was in turn associated with increased expression of KCNJ2-AS1 in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10-7). Thus, SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in FLJ22447 and 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).

Original languageEnglish
Article number2002693
Number of pages10
JournalEuropean Respiratory Journal
Issue number4
Early online date2020
Publication statusPublished - 1-Apr-2021


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