title: A genome-wide association study of asthma symptoms in Latin American children.
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.
authors.affiliation: Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil. gustavokosta@gmail.com.
authors.forename: Gustavo N O
authors.initials: GN
authors.lastname: Costa
authors.affiliation: Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. frank.dudbridge@lshtm.ac.uk.
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.affiliation: Instituto de Matemática, Universidade Federal da Bahia, Salvador, Brazil. rose.fiaccone@gmail.com.
authors.forename: Rosemeire L
authors.initials: RL
authors.lastname: Fiaccone
authors.affiliation: Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil. thiago@uesb.edu.br.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: da Silva
authors.affiliation: Instituto de Matemática, Universidade Federal da Bahia, Salvador, Brazil. jsantos1013@gmail.com.
authors.forename: Jackson S
authors.initials: JS
authors.lastname: Conceição
authors.affiliation: Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil. agstrina@yahoo.com.br.
authors.forename: Agostino
authors.initials: A
authors.lastname: Strina
authors.affiliation: Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil. cavfigueiredo@gmail.com.
authors.forename: Camila A
authors.initials: CA
authors.lastname: Figueiredo
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. wcsmagalhaes@gmail.com.
authors.forename: Wagner C S
authors.initials: WC
authors.lastname: Magalhães
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. maira.r.rodrigues@gmail.com.
authors.forename: Maira R
authors.initials: MR
authors.lastname: Rodrigues
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. mateushgbio@gmail.com.
authors.forename: Mateus H
authors.initials: MH
authors.lastname: Gouveia
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. fsgkehdy@yahoo.com.br.
authors.forename: Fernanda S G
authors.initials: FS
authors.lastname: Kehdy
authors.affiliation: Instituto do Coração, Universidade de São Paulo, São Paulo, Brazil. andreavrh@usp.br.
authors.forename: Andrea R V R
authors.initials: AR
authors.lastname: Horimoto
authors.affiliation: Programa de Pós Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Brazil. blhorta@gmail.com.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Horta
authors.affiliation: Department of Medicine, University of California, San Francisco, USA. esteban.burchard@ucsf.edu.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: Department of Medicine, University of California, San Francisco, USA. mdelpino@ull.edu.es.
authors.forename: Maria
authors.initials: M
authors.lastname: Pino-Yanes
authors.affiliation: 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.
authors.forename: Blanca
authors.initials: B
authors.lastname: Del Rio Navarro
authors.affiliation: Instituto Nacional de Salud Publica, Cuernavaca, Mexico. iromieu@gmail.com.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.affiliation: Behavioral and Urban Health Program, Research Triangle Institute (RTI) International, Research Triangle Park, North Carolina, USA. dhancock@rti.org.
authors.forename: Dana B
authors.initials: DB
authors.lastname: Hancock
authors.affiliation: 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.
authors.forename: Stephanie
authors.initials: S
authors.lastname: London
authors.affiliation: Instituto de Pesquisas Rene Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil. lima-costa@cpqrr.fiocruz.br.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Lima-Costa
authors.affiliation: Instituto de Pesquisas Rene Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil. alexandre.pereira@incor.usp.br.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. edutars@gmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tarazona
authors.affiliation: Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. laura.Rodrigues@lshtm.ac.uk.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Rodrigues
authors.affiliation: Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil. mauricio@ufba.br.|Centro de Pesquisa Gonçalo Muniz, Fundação Osvaldo Cruz, Salvador, Brazil. mauricio@ufba.br.
authors.forename: Mauricio L
authors.initials: ML
authors.lastname: Barreto
mesh_terms: D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007843:Latin America; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D025341:Principal Component Analysis