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

Joshua M. Galanter, Christopher R. Gignoux, Dara G. Torgerson, Lindsey A. Roth, Celeste Eng, Sam S. Oh, Elizabeth A. Nguyen, Katherine A. Drake, Scott Huntsman, Donglei Hu, Saunak Sen, Adam Davis, Harold J. Farber, Pedro C. Avila, Emerita Brigino-Buenaventura, Michael A. Lenoir, Kelley Meade, Denise Serebrisky, Luisa N. Borrell, William Rodríguez-CintrónAndres Moreno Estrada, Karla Sandoval Mendoza, Cheryl A. Winkler, William Klitz, Isabelle Romieu, Stephanie J. London, Frank Gilliland, Fernando Martinez, Carlos Bustamante, L. Keoki Williams, Rajesh Kumar, José R. Rodríguez-Santana, Esteban G. Burchard

Research output: Contribution to journalArticle

67 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)295-305
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number2
DOIs
StatePublished - Aug 2014

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study'. Together they form a unique fingerprint.

  • Cite this

    Galanter, J. M., Gignoux, C. R., Torgerson, D. G., Roth, L. A., Eng, C., Oh, S. S., Nguyen, E. A., Drake, K. A., Huntsman, S., Hu, D., Sen, S., Davis, A., Farber, H. J., Avila, P. C., Brigino-Buenaventura, E., Lenoir, M. A., Meade, K., Serebrisky, D., Borrell, L. N., ... Burchard, E. G. (2014). Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study. Journal of Allergy and Clinical Immunology, 134(2), 295-305. https://doi.org/10.1016/j.jaci.2013.08.055