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BMC Genet. 2015 Dec 3;16:141. doi: 10.1186/s12863-015-0296-7.

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

Author information

1
Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil. gustavokosta@gmail.com.
2
Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. frank.dudbridge@lshtm.ac.uk.
3
Instituto de Matemática, Universidade Federal da Bahia, Salvador, Brazil. rose.fiaccone@gmail.com.
4
Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil. thiago@uesb.edu.br.
5
Instituto de Matemática, Universidade Federal da Bahia, Salvador, Brazil. jsantos1013@gmail.com.
6
Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil. agstrina@yahoo.com.br.
7
Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil. cavfigueiredo@gmail.com.
8
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. wcsmagalhaes@gmail.com.
9
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. maira.r.rodrigues@gmail.com.
10
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. mateushgbio@gmail.com.
11
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. fsgkehdy@yahoo.com.br.
12
Instituto do Coração, Universidade de São Paulo, São Paulo, Brazil. andreavrh@usp.br.
13
Programa de Pós Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Brazil. blhorta@gmail.com.
14
Department of Medicine, University of California, San Francisco, USA. esteban.burchard@ucsf.edu.
15
Department of Medicine, University of California, San Francisco, USA. mdelpino@ull.edu.es.
16
Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. blancadelrionavarro@gmail.com.
17
Instituto Nacional de Salud Publica, Cuernavaca, Mexico. iromieu@gmail.com.
18
Behavioral and Urban Health Program, Research Triangle Institute (RTI) International, Research Triangle Park, North Carolina, USA. dhancock@rti.org.
19
Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. london2@niehs.nih.gov.
20
Instituto de Pesquisas Rene Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil. lima-costa@cpqrr.fiocruz.br.
21
Instituto de Pesquisas Rene Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil. alexandre.pereira@incor.usp.br.
22
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. edutars@gmail.com.
23
Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. laura.Rodrigues@lshtm.ac.uk.
24
Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil. mauricio@ufba.br.
25
Centro de Pesquisa Gonçalo Muniz, Fundação Osvaldo Cruz, Salvador, Brazil. mauricio@ufba.br.

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.

PMID:
26635092
PMCID:
PMC4669662
DOI:
10.1186/s12863-015-0296-7
[Indexed for MEDLINE]
Free PMC Article

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