Title
A genome-wide association study of asthma symptoms in Latin American children
Date Issued
03 December 2015
Access level
open access
Resource Type
journal article
Author(s)
Costa G.N.O.
Dudbridge F.
Fiaccone R.L.
da Silva T.M.
Conceição J.S.
Strina A.
Figueiredo C.A.
Magalhães W.C.S.
Rodrigues M.R.
Gouveia M.H.
Kehdy F.S.G.
Horimoto A.R.V.R.
Horta B.
Burchard E.G.
Pino-Yanes M.
Del Rio Navarro B.
Romieu I.
Hancock D.B.
London S.
Lima-Costa M.F.
Pereira A.C.
Rodrigues L.C.
Barreto M.L.
Universidade Federal de Minas Gerais
Publisher(s)
BioMed Central Ltd.
Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.
Volume
16
Issue
1
Language
English
OCDE Knowledge area
Pediatría
Sistema respiratorio
Subjects
Scopus EID
2-s2.0-84949234169
PubMed ID
Source
BMC Genetics
ISSN of the container
14712156
Sponsor(s)
This work was supported by the Department of Science and Technology (DECIT, Ministry of Health), National Fund for Scientific and Technological Development (FNDCT, Ministry of Science and Technology), Funding of Studies and Projects (FINEP, Ministry of Science and Technology, Brazil), the Brazilian National Research Council (CNPq) and the Wellcome Trust UK, Ref 072405/Z/03/Z. E.G.B. was funded by grants from National Institutes of Health (HL088133, HL078885, HL004464, HL104608, HL117004, ES015794 and MD006902) and by the American Asthma Foundation, the Sandler Foundation and the RWJF Amos Medical Faculty Development Award. Supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, USA.
Sources of information:
Directorio de Producción Científica
Scopus