Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations  Joshua M. Galanter, MD, Dara Torgerson, PhD,

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Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations  Joshua M. Galanter, MD, Dara Torgerson, PhD, Christopher R. Gignoux, MS, Saunak Sen, PhD, Lindsey A. Roth, MA, Marc Via, PhD, Melinda C. Aldrich, PhD, MPH, Celeste Eng, Scott Huntsman, MS, Jose Rodriguez-Santana, MD, William Rodriguez-Cintrón, MD, Rocio Chapela, MD, Jean G. Ford, MD, Esteban G. Burchard, MD, MPH  Journal of Allergy and Clinical Immunology  Volume 128, Issue 1, Pages 37-43.e12 (July 2011) DOI: 10.1016/j.jaci.2011.03.050 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 SNP and gene selection process. Journal of Allergy and Clinical Immunology 2011 128, 37-43.e12DOI: (10.1016/j.jaci.2011.03.050) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Box plot of individual ancestry estimates of GALA Mexican and Puerto Rican subjects. On average, Puerto Ricans have higher African and European ancestry than Mexicans, whereas Mexicans have higher Native American ancestry. ∗Significant difference between the groups. Journal of Allergy and Clinical Immunology 2011 128, 37-43.e12DOI: (10.1016/j.jaci.2011.03.050) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 SNP-based replication showing ORs (95% CI) for Mexican, Puerto Rican, and combined samples. The top graph shows the genes that replicated in the combined population with low heterogeneity, and the bottom graph shows genes that replicated in one population and had significant heterogeneity. Journal of Allergy and Clinical Immunology 2011 128, 37-43.e12DOI: (10.1016/j.jaci.2011.03.050) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Venn diagram showing the relationships between the replicated genes. An asterisk indicates that there was heterogeneity between ethnicities. Genes within boxes are additional genes identified only in the gene-based replication; the rest of the genes were identified in the SNP-based replication. In 3 genes (ie, ADRA1B, ORMDL3, and RAD50), different SNPs in the genes are associated differently, and therefore the gene is shown twice. Journal of Allergy and Clinical Immunology 2011 128, 37-43.e12DOI: (10.1016/j.jaci.2011.03.050) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Multidimensional scaling plot of the first 2 principal coordinates for GALA Puerto Rican and Mexican subjects. HapMap 3 European and African subjects and 4 populations of Native Americans are shown for comparison. Generally, Mexicans align on the axis between Europeans and Native Americans, whereas Puerto Ricans align in the axis between Europeans and Africans. Journal of Allergy and Clinical Immunology 2011 128, 37-43.e12DOI: (10.1016/j.jaci.2011.03.050) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 QQ-plot of the SNP-based replication comparing observed versus expected P values in Puerto Ricans, Mexicans, and the combined population. Journal of Allergy and Clinical Immunology 2011 128, 37-43.e12DOI: (10.1016/j.jaci.2011.03.050) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Genetic structure and linkage map of ORMDL3, a gene with strong associations in both Mexicans (top) and Puerto Ricans (bottom). SNP rs8076131 (left bold box) showed the strongest association in the combined sample and a significant association in each population. SNP rs4795408 (right bold box) showed a significant association in Mexicans but not Puerto Ricans. Journal of Allergy and Clinical Immunology 2011 128, 37-43.e12DOI: (10.1016/j.jaci.2011.03.050) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions