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

• Type of Material: Article
• Authors: Dara Torgerson, University of Chicago; Daniel Capurso, University of Chicago; Elizabeth J. Ampleford, Wake Forest School of Medicine; Xingnan Li, Wake Forest School of Medicine; Wendy Moore, Wake Forest School of Medicine; Christopher R. Gignoux, University of California at San Francisco; Donglei Hu, University of California at San Francisco; Celeste Eng, University of California at San Francisco; Rasika A. Mathias, Johns Hopkins Asthma and Allergy Center; William W. Busse, University of Wisconsin; Mario Castro, Washington University; Serpil C. Erzurum, The Lerner Research Institute; Anne M Fitzpatrick, Emory University; Benjamin Gaston, University of Virginia Health Systems; Elliot Israel, Harvard University; Nizar N. Jarjour, University of Wisconsin Hospital and Clinics; W. Gerald Teague, University of Virginia Health System; Sally E. Wenzel, University of Pittsburgh; Jose R. Rodriguez-Santana, Centro de Neumologia Pediatrica; William Rodriguez-Cintron, VA Medical Center; Pedro C. Avila, Northwestern University; Jean G. Ford, Johns Hopkins Bloomberg School of Public Health; Kathleen C. Barnes, Johns Hopkins Asthma and Allergy Center; Esteban G. Burchard, University of California at San Francisco; Timothy D. Howard, Wake Forest School of Medicine; Eugene R. Bleecker, Wake Forest School of Medicine; Deborah A. Meyers, Wake Forest School of Medicine; Nancy J. Cox, University of Chicago; Carole Ober, University of Chicago; Dan L. Nicolae, University of Chicago
• Language: English
• Date: 2012-09-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 American Academy of Allergy, Asthma & Immunology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jaci.2012.03.045
• Title of Journal or Parent Work: Journal of Allergy and Clinical Immunology
• ISSN: 0091-6749
• Volume: 130
• Issue: 3
• Start Page: 622
• End Page: +
• Grant/Funding Information: This work was supported by grants from the National Institute of Health (U01 HL49596, R01 HL072414, R01 HL087665, RC2 HL101651, 2T32GM007546, 1RC2 HL101651, ES015794, U19 AI077439, HL088133, HL078885), and the Flight Attendant Medical Research Institute (FAMRI).
• Keywords: African American; STRATIFICATION; CONSORTIUM; ancestry association testing; Science & Technology; Allergy; admixed populations; Life Sciences & Biomedicine; COMPONENTS; admixture mapping; LOCUS; Asthma; GENETICS; genome-wide association study; SCALE; Immunology; RESEARCH-PROGRAM; population structure; POPULATION; HERITABILITY; PHENOTYPES; Puerto Rican
• Research Categories: Health Sciences, Immunology; Health Sciences, General; Health Sciences, Epidemiology

Abstract

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.