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Author Notes:

Dan L. Nicolae, PhD, Department of Medicine, Section of Genetic Medicine, University of Chicago, 900 E 57th St, KCBD 3220, Chicago, IL 60637. E-mail: nicolae@galton.uchicago.edu.

See publication for full list of acknowledgements.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Allergy
  • Immunology
  • Asthma
  • population structure
  • genome-wide association study
  • admixture mapping
  • ancestry association testing
  • admixed populations
  • African American
  • Puerto Rican
  • RESEARCH-PROGRAM
  • POPULATION
  • LOCUS
  • STRATIFICATION
  • HERITABILITY
  • CONSORTIUM
  • PHENOTYPES
  • COMPONENTS
  • GENETICS
  • SCALE

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

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Journal Title:

Journal of Allergy and Clinical Immunology

Volume:

Volume 130, Number 3

Publisher:

, Pages 622-+

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2012 American Academy of Allergy, Asthma & Immunology.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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