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

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 La...

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Autores principales: Costa, Gustavo N. O., Dudbridge, Frank, Fiaccone, Rosemeire L., da Silva, Thiago M., Conceição, Jackson S., Strina, Agostino, Figueiredo, Camila A., Magalhães, Wagner C. S., Rodrigues, Maira R., Gouveia, Mateus H., Kehdy, Fernanda S. G., Horimoto, Andrea R. V. R., Horta, Bernardo, Burchard, Esteban G., Pino-Yanes, Maria, Del Rio Navarro, Blanca, Romieu, Isabelle, Hancock, Dana B., London, Stephanie, Lima-Costa, Maria Fernanda, Pereira, Alexandre C., Tarazona, Eduardo, Rodrigues, Laura C, Barreto, Mauricio L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669662/
https://www.ncbi.nlm.nih.gov/pubmed/26635092
http://dx.doi.org/10.1186/s12863-015-0296-7
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author Costa, Gustavo N. O.
Dudbridge, Frank
Fiaccone, Rosemeire L.
da Silva, Thiago M.
Conceição, Jackson S.
Strina, Agostino
Figueiredo, Camila A.
Magalhães, Wagner C. S.
Rodrigues, Maira R.
Gouveia, Mateus H.
Kehdy, Fernanda S. G.
Horimoto, Andrea R. V. R.
Horta, Bernardo
Burchard, Esteban G.
Pino-Yanes, Maria
Del Rio Navarro, Blanca
Romieu, Isabelle
Hancock, Dana B.
London, Stephanie
Lima-Costa, Maria Fernanda
Pereira, Alexandre C.
Tarazona, Eduardo
Rodrigues, Laura C
Barreto, Mauricio L.
author_facet Costa, Gustavo N. O.
Dudbridge, Frank
Fiaccone, Rosemeire L.
da Silva, Thiago M.
Conceição, Jackson S.
Strina, Agostino
Figueiredo, Camila A.
Magalhães, Wagner C. S.
Rodrigues, Maira R.
Gouveia, Mateus H.
Kehdy, Fernanda S. G.
Horimoto, Andrea R. V. R.
Horta, Bernardo
Burchard, Esteban G.
Pino-Yanes, Maria
Del Rio Navarro, Blanca
Romieu, Isabelle
Hancock, Dana B.
London, Stephanie
Lima-Costa, Maria Fernanda
Pereira, Alexandre C.
Tarazona, Eduardo
Rodrigues, Laura C
Barreto, Mauricio L.
author_sort Costa, Gustavo N. O.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The 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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spelling pubmed-46696622015-12-05 A genome-wide association study of asthma symptoms in Latin American children Costa, Gustavo N. O. Dudbridge, Frank Fiaccone, Rosemeire L. da Silva, Thiago M. Conceição, Jackson S. Strina, Agostino Figueiredo, Camila A. Magalhães, Wagner C. S. Rodrigues, Maira R. Gouveia, Mateus H. Kehdy, Fernanda S. G. Horimoto, Andrea R. V. R. Horta, Bernardo Burchard, Esteban G. Pino-Yanes, Maria Del Rio Navarro, Blanca Romieu, Isabelle Hancock, Dana B. London, Stephanie Lima-Costa, Maria Fernanda Pereira, Alexandre C. Tarazona, Eduardo Rodrigues, Laura C Barreto, Mauricio L. BMC Genet Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0296-7) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-03 /pmc/articles/PMC4669662/ /pubmed/26635092 http://dx.doi.org/10.1186/s12863-015-0296-7 Text en © Costa et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Costa, Gustavo N. O.
Dudbridge, Frank
Fiaccone, Rosemeire L.
da Silva, Thiago M.
Conceição, Jackson S.
Strina, Agostino
Figueiredo, Camila A.
Magalhães, Wagner C. S.
Rodrigues, Maira R.
Gouveia, Mateus H.
Kehdy, Fernanda S. G.
Horimoto, Andrea R. V. R.
Horta, Bernardo
Burchard, Esteban G.
Pino-Yanes, Maria
Del Rio Navarro, Blanca
Romieu, Isabelle
Hancock, Dana B.
London, Stephanie
Lima-Costa, Maria Fernanda
Pereira, Alexandre C.
Tarazona, Eduardo
Rodrigues, Laura C
Barreto, Mauricio L.
A genome-wide association study of asthma symptoms in Latin American children
title A genome-wide association study of asthma symptoms in Latin American children
title_full A genome-wide association study of asthma symptoms in Latin American children
title_fullStr A genome-wide association study of asthma symptoms in Latin American children
title_full_unstemmed A genome-wide association study of asthma symptoms in Latin American children
title_short A genome-wide association study of asthma symptoms in Latin American children
title_sort genome-wide association study of asthma symptoms in latin american children
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669662/
https://www.ncbi.nlm.nih.gov/pubmed/26635092
http://dx.doi.org/10.1186/s12863-015-0296-7
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