Case-control admixture mapping in Latino populations enriches for known asthma-associated genes - 27/06/12
, Christopher R. Gignoux, MS a, Joshua M. Galanter, MD a, Katherine A. Drake, MS a, Lindsey A. Roth, MA a, Celeste Eng, BS a, Scott Huntsman, MS a, Raul Torres, BS a, Pedro C. Avila, MD b, Rocio Chapela, MD c, Jean G. Ford, MD d, José R. Rodríguez-Santana, MD e, William Rodríguez-Cintrón, MD f, Ryan D. Hernandez, PhD g, Esteban G. Burchard, MD, MPH a, g
Corresponding author: Dara G. Torgerson, PhD, Department of Medicine, University of California San Francisco, 1550 4th St, San Francisco, CA 94158.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.
Le texte complet de cet article est disponible en PDF.Key words : Admixture mapping, genome-wide association study, asthma, Latino populations, population-specific risk factors
Abbreviations used : CEU, GALA, GWAS, LD, SNP, YRI
Plan
| Supported by grants from the National Institute of Health (HL088133 and HL078885 to E.G.B.), the National Institutes of Environmental Health Sciences (ES015794 to E.G.B.), the Flight Attendant Medical Research Institute, and the Sandler Foundation. |
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| Disclosure of potential conflict of interest: C. R. Gignoux owns stock in 23 and Me, Inc. P. C. Avila has received research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 130 - N° 1
P. 76 - juillet 2012 Retour au numéro
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