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


Costa, GN; Dudbridge, F; Fiaccone, RL; da Silva, TM; Conceição, JS; Strina, A; Figueiredo, CA; Magalhães, WC; Rodrigues, MR; Gouveia, MH; Kehdy, FS; Horimoto, AR; Horta, B; Burchard, EG; Pino-Yanes, M; Del Rio Navarro, B; Romieu, I; Hancock, DB; London, S; Lima-Costa, MF; Pereira, AC; Tarazona, E; Rodrigues, LC; Barreto, ML; (2015) A genome-wide association study of asthma symptoms in Latin American children. BMC Genet, 16 (1). p. 141. ISSN 1471-2156 DOI: 10.1186/s12863-015-0296-7

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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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Faculty of Epidemiology and Population Health
Research Centre: Centre for Maternal, Reproductive and Child Health (MARCH)
PubMed ID: 26635092
Web of Science ID: 365947200005
URI: http://researchonline.lshtm.ac.uk/id/eprint/2373958

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