@article{d991d94073ea4713856824983e63f310,
title = "Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects",
abstract = "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.",
keywords = "African American, Asthma, Puerto Rican, admixed populations, admixture mapping, ancestry association testing, genome-wide association study, population structure",
author = "Torgerson, {Dara G.} and Daniel Capurso and Ampleford, {Elizabeth J.} and Xingnan Li and Moore, {Wendy C.} and Gignoux, {Christopher R.} and Donglei Hu and Celeste Eng and Mathias, {Rasika A.} and Busse, {William W.} and Mario Castro and Erzurum, {Serpil C.} and Fitzpatrick, {Anne M.} and Benjamin Gaston and Elliot Israel and Jarjour, {Nizar N.} and Teague, {W. Gerald} and Wenzel, {Sally E.} and Rodr{\'i}guez-Santana, {Jos{\'e} R.} and William Rodr{\'i}guez-Cintr{\'o}n and Avila, {Pedro C.} and Ford, {Jean G.} and Barnes, {Kathleen C.} and Burchard, {Esteban G.} and Howard, {Timothy D.} and Bleecker, {Eugene R.} and Meyers, {Deborah A.} and Cox, {Nancy J.} and Carole Ober and Nicolae, {Dan L.}",
note = "Funding Information: Supported by grants from the National Institutes of Health ( U01 HL49596, R01 HL072414, R01 HL087665, RC2 HL101651, 2T32GM007546, 1RC2 HL101651, ES015794, U19 AI077439, HL088133, and HL078885 ) and the Flight Attendant Medical Research Institute (FAMRI). Funding Information: Disclosure of potential conflict of interest: C. R. Gignoux owns stock in 23 and Me, Inc. W. W. Busse is on the Advisory Board for Centocor and Merck; is a consultant for Amgen, AstraZeneca, Novartis, GlaxoSmithKline, MedImmune, and Genentech; has received research support from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) and NIH/National Heart, Lung, and Blood Institute (NHLBI) . M. Castro has given lectures for Asthmatx, Genentech, AstraZeneca, Merck, and GlaxoSmithKline; has consulted for Asthmatx; is on an advisory board for Genentech; and has received grants (given to his institution) from Asthmatx, Amgen, Ception/Cephalon, Genentech, Medimmune, Merck, Novartis, the NIH, and GlaxoSmithKline . B. Gaston has received research support from the Severe Asthma Research Network (SARP). W. G. Teague is a speaker for Merck and Genentech and has received research support from NIH/NHLBI and the American Lung Association . P. C. Avila has received research grants from Genentech and the NIH . J. G. Ford is a consultant for GlaxoSmithKline. K. C. Barnes has received research support from the NIH and Sirius Genomics, Inc . E. R. Bleecker and D. A. Meyers have received grants from the NIH . The rest of the authors declare that they have no relevant conflicts of interest. ",
year = "2012",
month = sep,
doi = "10.1016/j.jaci.2012.03.045",
language = "English (US)",
volume = "130",
pages = "622--629.e9",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",
}