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

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Presentation transcript:

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, PhD, Daniel Capurso, BS, Elizabeth J. Ampleford, PhD, Xingnan Li, PhD, Wendy C. Moore, MD, Christopher R. Gignoux, MS, Donglei Hu, PhD, Celeste Eng, BS, Rasika A. Mathias, ScD, William W. Busse, MD, Mario Castro, MD, Serpil C. Erzurum, MD, Anne M. Fitzpatrick, PhD, Benjamin Gaston, MD, Elliot Israel, MD, Nizar N. Jarjour, MD, W. Gerald Teague, MD, Sally E. Wenzel, MD, José R. Rodríguez-Santana, MD, William Rodríguez-Cintrón, MD, Pedro C. Avila, MD, Jean G. Ford, MD, Kathleen C. Barnes, PhD, Esteban G. Burchard, MD, Timothy D. Howard, PhD, Eugene R. Bleecker, MD, Deborah A. Meyers, PhD, Nancy J. Cox, PhD, Carole Ober, PhD, Dan L. Nicolae, PhD Journal of Allergy and Clinical Immunology Volume 130, Issue 3, Pages 622-629.e9 (September 2012) DOI: 10.1016/j.jaci.2012.03.045 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Results of genome-wide ancestry and allelic association testing in African American adults with asthma and healthy control subjects by using logistic regression. A, −log10(P values) across the genome showing the location of 4 ancestry association peaks with P values of less than .01 (above the dashed line). B, Average local European ancestry in the cases (red) and control subjects (blue) on chromosome 6; vertical lines indicate the boundaries of the ancestry association peak with a P value of less than .01, and the horizontal line indicates local European ancestry averaged across the genome. C, Tests of allelic association within the ancestry association peak on 6q in African American subjects (by using local ancestry as a covariate) and European American subjects in CSGA/SARP. Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Comparison of the observed distribution of P values to a uniform distribution by using the function qqplot in R for SNPs within the admixture mapping peak on chr6q. Local ancestry was included as a covariate in tests of association. Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Tests of allelic association controlling for local ancestry within 500 Kb of rs1361549 in African American subjects in CSGA/SARP at both genotyped and imputed SNPs from the 1000 Genomes Project. Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Principal component analysis of African American adults with asthma and healthy control subjects and the phase 3 HapMap CEU, YRI, and Asian (ASN) populations. Global estimates of European ancestry were extrapolated from PC1. Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Distribution of global European admixture in African American adults with asthma and nonasthmatic control subjects, as estimated from PC1. Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Correlation between mean local African ancestry calculated across the genome and estimates of global African ancestry from PC1. Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Estimates of local European ancestry in a single African American subject with asthma across chromosome 1 (top) and mean local European admixture across the genome in 444 nonasthmatic African American adults (bottom). Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 LD (r2) between genotyped SNPs in African American subjects with local European ancestry within a 100-Kb region centered on rs1361549. ∗Location of rs1361549. Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 LD (r2) between genotyped SNPs in African American subjects with local European ancestry at rs1361549 within a 1-Mb region centered on rs1361549. ∗Location of rs1361549. Journal of Allergy and Clinical Immunology 2012 130, 622-629.e9DOI: (10.1016/j.jaci.2012.03.045) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions