Background: Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated\ngenetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies\nhave been carried out in recent years, but none of these have involved Latin American populations with a high\nlevel of miscegenation, as is seen in the Brazilian population.\nMethods: 1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were\nidentified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire.\nFollowing quality control, 1 877 526 autosomal SNPs were tested for association with childhood asthma symptoms\nby logistic regression using an additive genetic model. We complemented the analysis with an estimate of the\nphenotypic variance explained by common genetic variants. Replications were investigated in independent\nMexican and US Latino samples.\nResults: Two chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the\n14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95 % CI 1.45ââ?¬â??2.18, p-value 2.83 Ã?â?? 10âË?â??8)\nand 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95 % CI 2.02ââ?¬â??4.49, p-value 6.68 Ã?â?? 10âË?â??8 and\nrs8029377, MAF 0.03, OR 2.49, 95 % CI 1.76ââ?¬â??3.53, p-value 2.45 Ã?â?? 10âË?â??7). eQTL analysis suggests that rs1999071 regulates\nthe expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples.\nConclusions: We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.
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