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J Allergy Clin Immunol. 2014 Aug;134(2):295-305. doi: 10.1016/j.jaci.2013.08.055. Epub 2014 Jan 7.

Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: the Genes-environments & Admixture in Latino Americans study.

Author information

  • 1Department 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.
  • 2Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
  • 3Department of Medicine, University of California, San Francisco, Calif.
  • 4School of Medicine, St Louis University, St Louis, Mo.
  • 5Department of Epidemiology & Biostatistics, University of California, San Francisco, Calif.
  • 6Children's Hospital and Research Center Oakland, Oakland, Calif.
  • 7Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex.
  • 8Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill.
  • 9Department of Allergy & Immunology, Kaiser Permanente-Vallejo Medical Center, Vallejo, Calif.
  • 10Bay Area Pediatrics, Oakland, Calif.
  • 11Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, NY.
  • 12Department of Health Sciences, Graduate Program in Public Health, Lehman College, City University of New York, Bronx, NY.
  • 13Veterans Caribbean Health Care System, San Juan, Puerto Rico.
  • 14Department of Genetics, Stanford University, Stanford, Calif.
  • 15Frederick National Laboratory for Cancer Research, National Institutes of Health, Frederick, Md.
  • 16School of Public Health, University of California, Berkeley, Calif.
  • 17International Agency for Research on Cancer, Lyon, France.
  • 18National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services, Research Triangle Park, NC.
  • 19Department of Preventive Medicine, University of Southern California, Los Angeles, Calif.
  • 20Department of Pediatrics, University of Arizona, Tucson, Ariz.
  • 21Department of Internal Medicine, Henry Ford Health System, Detroit, Mich.
  • 22Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill.
  • 23Centro de Neumologia Pediatrica, San Juan, Puerto Rico.
  • 24Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.

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.

Published by Mosby, Inc.

KEYWORDS:

17q21; 6p21; Asthma; Latinos; admixture mapping; genome-wide association study; local ancestry

PMID:
24406073
[PubMed - indexed for MEDLINE]
PMCID:
PMC4085159
Free PMC Article

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