Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects.

Torgerson DG, Capurso D, Ampleford EJ, Li X, Moore WC, Gignoux CR, Hu D, Eng C, Mathias RA, Busse WW, Castro M, Erzurum SC, Fitzpatrick AM, Gaston B, Israel E, Jarjour NN, Teague WG, Wenzel SE, Rodríguez-Santana JR, Rodríguez-Cintrón W, Avila PC, Ford JG, Barnes KC, Burchard EG, Howard TD, Bleecker ER, Meyers DA, Cox NJ, Ober C, Nicolae DL
J Allergy Clin Immunol. 2012 130 (3): 622-629.e9

PMID: 22607992 · PMCID: PMC3503456 · DOI:10.1016/j.jaci.2012.03.045

BACKGROUND - Genetic variants that contribute to asthma susceptibility might be present at varying frequencies in different populations, which is an important consideration and advantage for performing genetic association studies in admixed populations.

OBJECTIVE - We sought to identify asthma-associated loci in African American subjects.

METHODS - We compared local African and European ancestry estimated from dense single nucleotide polymorphism genotype data in African American adults with asthma and nonasthmatic control subjects. Allelic tests of association were performed within the candidate regions identified, correcting for local European admixture.

RESULTS - We identified a significant ancestry association peak on chromosome 6q. Allelic tests for association within this region identified a single nucleotide polymorphism (rs1361549) on 6q14.1 that was associated with asthma exclusively in African American subjects with local European admixture (odds ratio, 2.2). The risk allele is common in Europe (42% in the HapMap population of Utah residents with Northern and Western European ancestry from the Centre d'Etude du Polymorphisme Humain collection) but absent in West Africa (0% in the HapMap population of Yorubans in Ibadan, Nigeria), suggesting the allele is present in African American subjects because of recent European admixture. We replicated our findings in Puerto Rican subjects and similarly found that the signal of association is largely specific to subjects who are heterozygous for African and non-African ancestry at 6q14.1. However, we found no evidence for association in European American or Puerto Rican subjects in the absence of local African ancestry, suggesting that the association with asthma at rs1361549 is due to an environmental or genetic interaction.

CONCLUSION - We identified a novel asthma-associated locus that is relevant to admixed populations with African ancestry and highlight the importance of considering local ancestry in genetic association studies of admixed populations.

Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

MeSH Terms (9)

African Americans Asthma Chromosomes, Human, Pair 6 European Continental Ancestry Group Genome-Wide Association Study Humans Linkage Disequilibrium Polymorphism, Single Nucleotide Risk Factors

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