Rasika A. Mathias, ScD, Audrey V

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Presentation transcript:

A genome-wide association study on African-ancestry populations for asthma Rasika A. Mathias, ScD, Audrey V. Grant, PhD, Nicholas Rafaels, MS, Tracey Hand, MS, Li Gao, MD, PhD, Candelaria Vergara, MSc, Yuhjung J. Tsai, MD, Mao Yang, MS, Monica Campbell, BS, Cassandra Foster, Peisong Gao, MD, PhD, A. Togias, MD, Nadia N. Hansel, MD, MPH, Gregory Diette, MD, N. Franklin Adkinson, MD, Mark C. Liu, MD, Mezbah Faruque, MD, PhD, Georgia M. Dunston, PhD, Harold R. Watson, MD, Michael B. Bracken, PhD, Josephine Hoh, PhD, Pissamai Maul, RN, Trevor Maul, RN, Anne E. Jedlicka, MS, Tanda Murray, MS, Jacqueline B. Hetmanski, MS, Roxann Ashworth, MHS, Chrissie M. Ongaco, BS, Kurt N. Hetrick, MS, Kimberly F. Doheny, PhD, Elizabeth W. Pugh, PhD, MPH, Charles N. Rotimi, PhD, Jean Ford, MD, Celeste Eng, BS, Esteban G. Burchard, MD, Patrick M.A. Sleiman, PhD, Hakon Hakonarson, MD, PhD, Erick Forno, MD, Benjamin A. Raby, MD, Scott T. Weiss, MD, Alan F. Scott, PhD, Michael Kabesch, MD, Liming Liang, MS, Gonçalo Abecasis, PhD, Miriam F. Moffatt, PhD, William O.C. Cookson, MD, Ingo Ruczinski, PhD, Terri H. Beaty, PhD, Kathleen C. Barnes, PhD Journal of Allergy and Clinical Immunology Volume 125, Issue 2, Pages 336-346.e4 (February 2010) DOI: 10.1016/j.jaci.2009.08.031 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Triangle plots showing estimated admixture in 2 populations of African descent. Estimates were performed using 416 AIMs and data from the International HapMap Project on 60 YRI, 60 CEU, 90 CHB/JPT founders (see text for details). The figure depicts ancestry in 447 African American asthmatic cases and 459 nonasthmatic control subjects (A) and 298 African Caribbean founders (B). Journal of Allergy and Clinical Immunology 2010 125, 336-346.e4DOI: (10.1016/j.jaci.2009.08.031) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Genome-wide associations for asthma in 2 populations of African descent. A, African American asthmatic cases and control subjects. B, African Caribbean families. C, Meta-analysis of African American and African Caribbean GRAAD samples. Note that for visual clarity, the y-axis was truncated at a −log10(P value) of 9, resulting in the exclusion of a single data point (Fig 2, A: rs13209883, P = 2.77 × 10−11). Journal of Allergy and Clinical Immunology 2010 125, 336-346.e4DOI: (10.1016/j.jaci.2009.08.031) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Evidence of association with asthma and LD around ADRA1B, PRNP, and DPP10. Upper plots summarize association P values for all genotyped and imputed SNPs in the African American case-control group for ADRA1B(A), PRNP(B), and DPP10(C). Lower plots illustrate patterns of LD (R2) in these samples: red squares for strong LD, blue squares for nonsignificant LD, and white squares for little or no LD. Journal of Allergy and Clinical Immunology 2010 125, 336-346.e4DOI: (10.1016/j.jaci.2009.08.031) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Evidence of association with asthma and LD around DPP10. The upper plot summarizes association P values of genotyped and imputed SNPs for the African American cases and control subjects, African Caribbean families, and the European GABRIEL replicate population. Lower plots illustrate patterns of LD (R2) in these samples: red squares for strong LD, blue squares for nonsignificant LD, and white squares for little or no LD. Journal of Allergy and Clinical Immunology 2010 125, 336-346.e4DOI: (10.1016/j.jaci.2009.08.031) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Expected quantiles versus observed quantiles for the −log10P values in the GRAAD and Barbados populations. The red dots flag SNPs with MAF <1% and the gray region indicates the 95% confidence band, which was calculated by using the Stirling approximation.E1 Journal of Allergy and Clinical Immunology 2010 125, 336-346.e4DOI: (10.1016/j.jaci.2009.08.031) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Evidence of association with asthma and LD around the genes ADRA1B, PRNP, and DPP10. Upper plots summarize all genotyped (dark green circles) or imputed (light green circles) SNPs with association P values (additive test) in the African Caribbean family-based group for ADRA1B(A), PRNP(B), and DPP10(C). Lower plots in each panel illustrate patterns of LD (R2) in the samples represented as red squares for strong LD, blue squares for nonsignificant LD, and white squares for little or no LD. Journal of Allergy and Clinical Immunology 2010 125, 336-346.e4DOI: (10.1016/j.jaci.2009.08.031) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions