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

Dara G. Torgerson, Daniel Capurso, Elizabeth J. Ampleford, Xingnan Li, Wendy C. Moore, Christopher R. Gignoux, Donglei Hu, Celeste Eng, Rasika Mathias, William W. Busse, Mario Castro, Serpil C. Erzurum, Anne M. Fitzpatrick, Benjamin Gaston, Elliot Israel, Nizar N. Jarjour, W. Gerald Teague, Sally E. Wenzel, José R. Rodríguez-Santana, William Rodríguez-CintrónPedro C. Avila, Jean G. Ford, Kathleen C. Barnes, Esteban G. Burchard, Timothy D. Howard, Eugene R. Bleecker, Deborah A. Meyers, Nancy J. Cox, Carole Ober, Dan L. Nicolae

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalThe Journal of Allergy and Clinical Immunology
Volume130
Issue number3
DOIs
StatePublished - Sep 2012

Fingerprint

African Americans
Asthma
Genome
HapMap Project
Population
Genetic Association Studies
Hispanic Americans
Single Nucleotide Polymorphism
Alleles
Western Africa
Nigeria
Chromosomes
Odds Ratio
Genotype

Keywords

  • admixed populations
  • admixture mapping
  • African American
  • ancestry association testing
  • Asthma
  • genome-wide association study
  • population structure
  • Puerto Rican

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects. / Torgerson, Dara G.; Capurso, Daniel; Ampleford, Elizabeth J.; Li, Xingnan; Moore, Wendy C.; Gignoux, Christopher R.; Hu, Donglei; Eng, Celeste; Mathias, Rasika; Busse, William W.; Castro, Mario; Erzurum, Serpil C.; Fitzpatrick, Anne M.; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar N.; Teague, W. Gerald; Wenzel, Sally E.; Rodríguez-Santana, José R.; Rodríguez-Cintrón, William; Avila, Pedro C.; Ford, Jean G.; Barnes, Kathleen C.; Burchard, Esteban G.; Howard, Timothy D.; Bleecker, Eugene R.; Meyers, Deborah A.; Cox, Nancy J.; Ober, Carole; Nicolae, Dan L.

In: The Journal of Allergy and Clinical Immunology, Vol. 130, No. 3, 09.2012.

Research output: Contribution to journalArticle

Torgerson, DG, Capurso, D, Ampleford, EJ, Li, X, Moore, WC, Gignoux, CR, Hu, D, Eng, C, Mathias, R, 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 2012, 'Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects', The Journal of Allergy and Clinical Immunology, vol. 130, no. 3. https://doi.org/10.1016/j.jaci.2012.03.045
Torgerson, Dara G. ; Capurso, Daniel ; Ampleford, Elizabeth J. ; Li, Xingnan ; Moore, Wendy C. ; Gignoux, Christopher R. ; Hu, Donglei ; Eng, Celeste ; Mathias, Rasika ; Busse, William W. ; Castro, Mario ; Erzurum, Serpil C. ; Fitzpatrick, Anne M. ; Gaston, Benjamin ; Israel, Elliot ; Jarjour, Nizar N. ; Teague, W. Gerald ; Wenzel, Sally E. ; Rodríguez-Santana, José R. ; Rodríguez-Cintrón, William ; Avila, Pedro C. ; Ford, Jean G. ; Barnes, Kathleen C. ; Burchard, Esteban G. ; Howard, Timothy D. ; Bleecker, Eugene R. ; Meyers, Deborah A. ; Cox, Nancy J. ; Ober, Carole ; Nicolae, Dan L. / Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects. In: The Journal of Allergy and Clinical Immunology. 2012 ; Vol. 130, No. 3.
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T1 - Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects

AU - Torgerson, Dara G.

AU - Capurso, Daniel

AU - Ampleford, Elizabeth J.

AU - Li, Xingnan

AU - Moore, Wendy C.

AU - Gignoux, Christopher R.

AU - Hu, Donglei

AU - Eng, Celeste

AU - Mathias, Rasika

AU - Busse, William W.

AU - Castro, Mario

AU - Erzurum, Serpil C.

AU - Fitzpatrick, Anne M.

AU - Gaston, Benjamin

AU - Israel, Elliot

AU - Jarjour, Nizar N.

AU - Teague, W. Gerald

AU - Wenzel, Sally E.

AU - Rodríguez-Santana, José R.

AU - Rodríguez-Cintrón, William

AU - Avila, Pedro C.

AU - Ford, Jean G.

AU - Barnes, Kathleen C.

AU - Burchard, Esteban G.

AU - Howard, Timothy D.

AU - Bleecker, Eugene R.

AU - Meyers, Deborah A.

AU - Cox, Nancy J.

AU - Ober, Carole

AU - Nicolae, Dan L.

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

KW - admixed populations

KW - admixture mapping

KW - African American

KW - ancestry association testing

KW - Asthma

KW - genome-wide association study

KW - population structure

KW - Puerto Rican

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