A Genome-Wide Association Study of Severe Asthma Exacerbations in Latino Children and Adolescents

Abstract

Asthma is the most common chronic respiratory disease among children, and, although, in genome-wide association studies, researchers have identified specific loci related to asthma, there is little known about genetic determinants of asthma exacerbations. Recent evidence suggests some susceptibility variants for asthma-related outcomes are ethnicity specific. The purpose of this study was to investigate the effect of these susceptibility variants in Latino subgroups by performing a meta-analysis of genome-wide association studies of severe asthma exacerbations among Hispanic youth with asthma.This meta-analysis involved 4 separate studies (Hartford Puerto Rico study, the Genetics of Asthma in Latino Americans study, the Genetics of Asthma in Costa Rica study, and the Social Change, Asthma and Allergy in Latin America study) with a population of 4010 Latino children (1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians, and 402 members from other Latino subgroups). A total of 2509 individuals with asthma and ≥1 severe asthma exacerbation were included as cases, and 1501 individuals with asthma but no severe asthma exacerbation were included as controls.Methylation quantitative trait locus, expression quantitative trait locus, and expression quantitative trait methylation analyses were conducted to assess if the top single-nucleotide polymorphism (SNP) identified in the meta-analysis was linked to DNA methylation and gene expression in airway epithelium.In this meta-analysis, researchers found 1 SNP (rs2253681) in the FLJ22447 locus on chromosome 14q23.2 that was significantly associated with severe asthma exacerbations (P < 5 × 10−8). Each copy of the minor allele of SNP rs2253681 was associated with 1.55 times increased odds of severe asthma exacerbations (95% confidence interval: 1.34 to 1.79; P = 6.3 × 10−9).SNP rs2253681 was found to be significantly associated with severe asthma exacerbations in Latino children and adolescents with asthma.This study reveals the potential utility of genomics in the counseling and management of asthma. As more genetic mutations associated with asthma and asthma outcomes are identified, the better we can understand genetic components of this disease and can develop targeted therapies on the basis of gene-specific changes. Further genomic studies are needed to identify mutations associated with airway function and severe asthma exacerbations to identify those at risk for worse outcomes and those who may respond better to certain therapies on the basis of genetics.