Case-control admixture mapping in Latino populations enriches for known asthma-associated genes

Dara G. Torgerson, Christopher R. Gignoux, Joshua M. Galanter, Katherine A. Drake, Lindsey A. Roth, Celeste Eng, Scott Huntsman, Raul Torres, Pedro C. Avila, Rocio Chapela, Jean G. Ford, José R. Rodríguez-Santana, William Rodríguez-Cintrón, Ryan D. Hernandez, Esteban G. Burchard

Research output: Contribution to journalArticle

Abstract

Background: Polymorphisms in more than 100 genes have been associated with asthma susceptibility, yet much of the heritability remains to be explained. Asthma disproportionately affects different racial and ethnic groups in the United States, suggesting that admixture mapping is a useful strategy to identify novel asthma-associated loci. Objective: We sought to identify novel asthma-associated loci in Latino populations using case-control admixture mapping. Methods: We performed genome-wide admixture mapping by comparing levels of local Native American, European, and African ancestry between children with asthma and nonasthmatic control subjects in Puerto Rican and Mexican populations. Within candidate peaks, we performed allelic tests of association, controlling for differences in local ancestry. Results: Between the 2 populations, we identified a total of 62 admixture mapping peaks at a P value of less than 10 -3 that were significantly enriched for previously identified asthma-associated genes (P =.0051). One of the peaks was statistically significant based on 100 permutations in the Mexican sample (6q15); however, it was not significant in Puerto Rican subjects. Another peak was identified at nominal significance in both populations (8q12); however, the association was observed with different ancestries. Conclusion: Case-control admixture mapping is a promising strategy for identifying novel asthma-associated loci in Latino populations and implicates genetic variation at 6q15 and 8q12 regions with asthma susceptibility. This approach might be useful for identifying regions that contribute to both shared and population-specific differences in asthma susceptibility.

Original languageEnglish (US)
JournalThe Journal of Allergy and Clinical Immunology
Volume130
Issue number1
DOIs
StatePublished - Jul 2012

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Hispanic Americans
Asthma
Population
Genes
North American Indians
Population Genetics
Ethnic Groups
Genome

Keywords

  • Admixture mapping
  • asthma
  • genome-wide association study
  • Latino populations
  • population-specific risk factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Torgerson, D. G., Gignoux, C. R., Galanter, J. M., Drake, K. A., Roth, L. A., Eng, C., ... Burchard, E. G. (2012). Case-control admixture mapping in Latino populations enriches for known asthma-associated genes. The Journal of Allergy and Clinical Immunology, 130(1). https://doi.org/10.1016/j.jaci.2012.02.040

Case-control admixture mapping in Latino populations enriches for known asthma-associated genes. / Torgerson, Dara G.; Gignoux, Christopher R.; Galanter, Joshua M.; Drake, Katherine A.; Roth, Lindsey A.; Eng, Celeste; Huntsman, Scott; Torres, Raul; Avila, Pedro C.; Chapela, Rocio; Ford, Jean G.; Rodríguez-Santana, José R.; Rodríguez-Cintrón, William; Hernandez, Ryan D.; Burchard, Esteban G.

In: The Journal of Allergy and Clinical Immunology, Vol. 130, No. 1, 07.2012.

Research output: Contribution to journalArticle

Torgerson, DG, Gignoux, CR, Galanter, JM, Drake, KA, Roth, LA, Eng, C, Huntsman, S, Torres, R, Avila, PC, Chapela, R, Ford, JG, Rodríguez-Santana, JR, Rodríguez-Cintrón, W, Hernandez, RD & Burchard, EG 2012, 'Case-control admixture mapping in Latino populations enriches for known asthma-associated genes', The Journal of Allergy and Clinical Immunology, vol. 130, no. 1. https://doi.org/10.1016/j.jaci.2012.02.040
Torgerson, Dara G. ; Gignoux, Christopher R. ; Galanter, Joshua M. ; Drake, Katherine A. ; Roth, Lindsey A. ; Eng, Celeste ; Huntsman, Scott ; Torres, Raul ; Avila, Pedro C. ; Chapela, Rocio ; Ford, Jean G. ; Rodríguez-Santana, José R. ; Rodríguez-Cintrón, William ; Hernandez, Ryan D. ; Burchard, Esteban G. / Case-control admixture mapping in Latino populations enriches for known asthma-associated genes. In: The Journal of Allergy and Clinical Immunology. 2012 ; Vol. 130, No. 1.
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abstract = "Background: Polymorphisms in more than 100 genes have been associated with asthma susceptibility, yet much of the heritability remains to be explained. Asthma disproportionately affects different racial and ethnic groups in the United States, suggesting that admixture mapping is a useful strategy to identify novel asthma-associated loci. Objective: We sought to identify novel asthma-associated loci in Latino populations using case-control admixture mapping. Methods: We performed genome-wide admixture mapping by comparing levels of local Native American, European, and African ancestry between children with asthma and nonasthmatic control subjects in Puerto Rican and Mexican populations. Within candidate peaks, we performed allelic tests of association, controlling for differences in local ancestry. Results: Between the 2 populations, we identified a total of 62 admixture mapping peaks at a P value of less than 10 -3 that were significantly enriched for previously identified asthma-associated genes (P =.0051). One of the peaks was statistically significant based on 100 permutations in the Mexican sample (6q15); however, it was not significant in Puerto Rican subjects. Another peak was identified at nominal significance in both populations (8q12); however, the association was observed with different ancestries. Conclusion: Case-control admixture mapping is a promising strategy for identifying novel asthma-associated loci in Latino populations and implicates genetic variation at 6q15 and 8q12 regions with asthma susceptibility. This approach might be useful for identifying regions that contribute to both shared and population-specific differences in asthma susceptibility.",
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AU - Drake, Katherine A.

AU - Roth, Lindsey A.

AU - Eng, Celeste

AU - Huntsman, Scott

AU - Torres, Raul

AU - Avila, Pedro C.

AU - Chapela, Rocio

AU - Ford, Jean G.

AU - Rodríguez-Santana, José R.

AU - Rodríguez-Cintrón, William

AU - Hernandez, Ryan D.

AU - Burchard, Esteban G.

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N2 - Background: Polymorphisms in more than 100 genes have been associated with asthma susceptibility, yet much of the heritability remains to be explained. Asthma disproportionately affects different racial and ethnic groups in the United States, suggesting that admixture mapping is a useful strategy to identify novel asthma-associated loci. Objective: We sought to identify novel asthma-associated loci in Latino populations using case-control admixture mapping. Methods: We performed genome-wide admixture mapping by comparing levels of local Native American, European, and African ancestry between children with asthma and nonasthmatic control subjects in Puerto Rican and Mexican populations. Within candidate peaks, we performed allelic tests of association, controlling for differences in local ancestry. Results: Between the 2 populations, we identified a total of 62 admixture mapping peaks at a P value of less than 10 -3 that were significantly enriched for previously identified asthma-associated genes (P =.0051). One of the peaks was statistically significant based on 100 permutations in the Mexican sample (6q15); however, it was not significant in Puerto Rican subjects. Another peak was identified at nominal significance in both populations (8q12); however, the association was observed with different ancestries. Conclusion: Case-control admixture mapping is a promising strategy for identifying novel asthma-associated loci in Latino populations and implicates genetic variation at 6q15 and 8q12 regions with asthma susceptibility. This approach might be useful for identifying regions that contribute to both shared and population-specific differences in asthma susceptibility.

AB - Background: Polymorphisms in more than 100 genes have been associated with asthma susceptibility, yet much of the heritability remains to be explained. Asthma disproportionately affects different racial and ethnic groups in the United States, suggesting that admixture mapping is a useful strategy to identify novel asthma-associated loci. Objective: We sought to identify novel asthma-associated loci in Latino populations using case-control admixture mapping. Methods: We performed genome-wide admixture mapping by comparing levels of local Native American, European, and African ancestry between children with asthma and nonasthmatic control subjects in Puerto Rican and Mexican populations. Within candidate peaks, we performed allelic tests of association, controlling for differences in local ancestry. Results: Between the 2 populations, we identified a total of 62 admixture mapping peaks at a P value of less than 10 -3 that were significantly enriched for previously identified asthma-associated genes (P =.0051). One of the peaks was statistically significant based on 100 permutations in the Mexican sample (6q15); however, it was not significant in Puerto Rican subjects. Another peak was identified at nominal significance in both populations (8q12); however, the association was observed with different ancestries. Conclusion: Case-control admixture mapping is a promising strategy for identifying novel asthma-associated loci in Latino populations and implicates genetic variation at 6q15 and 8q12 regions with asthma susceptibility. This approach might be useful for identifying regions that contribute to both shared and population-specific differences in asthma susceptibility.

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