title: Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: the Genes-environments & Admixture in Latino Americans study.
abstract: BACKGROUND
  Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent.
  
  
  OBJECTIVE
  We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping.
  
  
  METHODS
  Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci.
  
  
  RESULTS
  We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies.
  
  
  CONCLUSIONS
  Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21.
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif. Electronic address: joshua.galanter@ucsf.edu.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Galanter
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gignoux
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Dara G
authors.initials: DG
authors.lastname: Torgerson
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Roth
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Sam S
authors.initials: SS
authors.lastname: Oh
authors.affiliation: School of Medicine, St Louis University, St Louis, Mo.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Nguyen
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Drake
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Epidemiology & Biostatistics, University of California, San Francisco, Calif.
authors.forename: Saunak
authors.initials: S
authors.lastname: Sen
authors.affiliation: Children's Hospital and Research Center Oakland, Oakland, Calif.
authors.forename: Adam
authors.initials: A
authors.lastname: Davis
authors.affiliation: Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Farber
authors.affiliation: Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.affiliation: Department of Allergy & Immunology, Kaiser Permanente-Vallejo Medical Center, Vallejo, Calif.
authors.forename: Emerita
authors.initials: E
authors.lastname: Brigino-Buenaventura
authors.affiliation: Bay Area Pediatrics, Oakland, Calif.
authors.forename: Michael A
authors.initials: MA
authors.lastname: LeNoir
authors.affiliation: Children's Hospital and Research Center Oakland, Oakland, Calif.
authors.forename: Kelley
authors.initials: K
authors.lastname: Meade
authors.affiliation: Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, NY.
authors.forename: Denise
authors.initials: D
authors.lastname: Serebrisky
authors.affiliation: Department of Health Sciences, Graduate Program in Public Health, Lehman College, City University of New York, Bronx, NY.
authors.forename: Luisa N
authors.initials: LN
authors.lastname: Borrell
authors.affiliation: Veterans Caribbean Health Care System, San Juan, Puerto Rico.
authors.forename: William
authors.initials: W
authors.lastname: Rodríguez-Cintrón
authors.affiliation: Department of Genetics, Stanford University, Stanford, Calif.
authors.forename: Andres Moreno
authors.initials: AM
authors.lastname: Estrada
authors.affiliation: Department of Genetics, Stanford University, Stanford, Calif.
authors.forename: Karla Sandoval
authors.initials: KS
authors.lastname: Mendoza
authors.affiliation: Frederick National Laboratory for Cancer Research, National Institutes of Health, Frederick, Md.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.affiliation: School of Public Health, University of California, Berkeley, Calif.
authors.forename: William
authors.initials: W
authors.lastname: Klitz
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services, Research Triangle Park, NC.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, Calif.
authors.forename: Frank
authors.initials: F
authors.lastname: Gilliland
authors.affiliation: Department of Pediatrics, University of Arizona, Tucson, Ariz.
authors.forename: Fernando
authors.initials: F
authors.lastname: Martinez
authors.affiliation: Department of Genetics, Stanford University, Stanford, Calif.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bustamante
authors.affiliation: Department of Internal Medicine, Henry Ford Health System, Detroit, Mich.
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
authors.affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Centro de Neumologia Pediatrica, San Juan, Puerto Rico.
authors.forename: José R
authors.initials: JR
authors.lastname: Rodríguez-Santana
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002896:Chromosomes, Human, Pair 6; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D014481:United States; D055815:Young Adult
chemical_list: C106285:IKZF3 protein, human; C484393:PSORS1C1 protein, human; D011506:Proteins; D051740:Ikaros Transcription Factor
keywords: 17q21; 6p21; Asthma; Latinos; admixture mapping; genome-wide association study; local ancestry