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A genome-wide association study of asthma symptoms in Latin American children.

ABSTRACT: Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population.1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were identified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Following quality control, 1,877,526 autosomal SNPs were tested for association with childhood asthma symptoms by logistic regression using an additive genetic model. We complemented the analysis with an estimate of the phenotypic variance explained by common genetic variants. Replications were investigated in independent Mexican and US Latino samples.Two chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the 14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95% CI 1.45-2.18, p-value 2.83?×?10(-8)) and 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95% CI 2.02-4.49, p-value 6.68?×?10(-8) and rs8029377, MAF 0.03, OR 2.49, 95% CI 1.76-3.53, p-value 2.45?×?10(-7)). eQTL analysis suggests that rs1999071 regulates the expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples.We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.

SUBMITTER: Costa GN

PROVIDER: S-EPMC4669662 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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A genome-wide association study of asthma symptoms in Latin American children.

Costa Gustavo N O GN Dudbridge Frank F Fiaccone Rosemeire L RL da Silva Thiago M TM Conceição Jackson S JS Strina Agostino A Figueiredo Camila A CA Magalhães Wagner C S WC Rodrigues Maira R MR Gouveia Mateus H MH Kehdy Fernanda S G FS Horimoto Andrea R V R AR Horta Bernardo B Burchard Esteban G EG Pino-Yanes Maria M Del Rio Navarro Blanca B Romieu Isabelle I Hancock Dana B DB London Stephanie S Lima-Costa Maria Fernanda MF Pereira Alexandre C AC Tarazona Eduardo E Rodrigues Laura C LC Barreto Mauricio L ML

BMC genetics 20151203

<h4>Background</h4>Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population.<h4>Methods</h4>1246 children were recruited from a longitudinal cohort study in Salvador, Br ...[more]

PMID: 26635092

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Project description:BackgroundInhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response.ObjectiveWe aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings.MethodsA meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10-6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations.ResultsA total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10-6 ). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10-3 ) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10-3 ). Additionally, the reported association of the L3MBTL4-ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified.Conclusions and clinical relevanceThis study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.

Dataset Information

A genome-wide association study of asthma symptoms in Latin American children.

Publications

A genome-wide association study of asthma symptoms in Latin American children.

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