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BMC Genetics

, 16:141

Human population genetics

Abstract

BackgroundAsthma 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.

Methods1246 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.

ResultsTwo 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 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 and rs8029377, MAF 0.03, OR 2.49, 95 % CI 1.76–3.53, p-value 2.45 × 10. 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.

ConclusionsWe conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.

KeywordsAsthma symptoms Genome-wide association Latin America Children AbbreviationsGWASGenome-Wide Association Studies

SNPsSingle Nucleotide Polymorphisms

MAFMinor allele frequency

OROdds Ratio

95 %CI95 % Confidence Interval

SPTSkin Prick Test

PCAPrincipal Component Analysis

GTExGenotype-Tissue Expression

GOGene Ontology

GCTAGenome-wide Complex Trait Analysis

SCAALASocial Changes, Asthma and Allergy in Latin America

ISAACInternational Study of Asthma and Allergies in Childhood

GALA IIGenes-environments and Admixture in Latino Americans

MCCASMexico City Childhood Asthma Study

Electronic supplementary materialThe online version of this article doi:10.1186-s12863-015-0296-7 contains supplementary material, which is available to authorized users.

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Author: Gustavo N. O. Costa - Frank Dudbridge - Rosemeire L. Fiaccone - Thiago M. da Silva - Jackson S. Conceição - Agostino 

Source: https://link.springer.com/



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