Genome-wide association study and admixture mapping identify different asthma- associated loci in Latinos: The Genes-environments & Admixture in Latino.

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Genome-wide association study and admixture mapping identify different asthma- associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study Joshua M. Galanter, MD, MAS, Christopher R. Gignoux, MS, Dara G. Torgerson, PhD, Lindsey A. Roth, MA, Celeste Eng, BS, Sam S. Oh, MPH, PhD, Elizabeth A. Nguyen, BS, Katherine A. Drake, PhD, Scott Huntsman, MS, Donglei Hu, PhD, Saunak Sen, PhD, Adam Davis, MA, MPH, Harold J. Farber, MD, MSPH, Pedro C. Avila, MD, Emerita Brigino-Buenaventura, MD, Michael A. LeNoir, MD, Kelley Meade, MD, Denise Serebrisky, MD, Luisa N. Borrell, DDS, PhD, William Rodríguez-Cintrón, MD, Andres Moreno Estrada, MD, PhD, Karla Sandoval Mendoza, MS, PhD, Cheryl A. Winkler, PhD, William Klitz, PhD, Isabelle Romieu, MD, MPH, Stephanie J. London, MD, DrPh, Frank Gilliland, MD, PhD, Fernando Martinez, MD, Carlos Bustamante, MA, PhD, L. Keoki Williams, MD, MPH, Rajesh Kumar, MD, José R. Rodríguez-Santana, MD, Esteban G. Burchard, MD, MPH Journal of Allergy and Clinical Immunology Volume 134, Issue 2, Pages 295-305 (August 2014) DOI: 10.1016/j.jaci.2013.08.055 Copyright © 2014 Terms and Conditions

Fig 1 Proportions of individual Native American, European, and African ancestry in the GALA II participants. Each bar represents 1 subject. There is substantial variability in individual ancestry both within and between Latino ethnic subgroups. Journal of Allergy and Clinical Immunology 2014 134, 295-305DOI: (10.1016/j.jaci.2013.08.055) Copyright © 2014 Terms and Conditions

Fig 2 Admixture mapping results. A, Manhattan plot of the admixture mapping study showing a significant peak in chromosome 6. The red line represents the fifth percentile of the lowest P value in 10,000 permutations. B, LocusZoom plot of the admixture mapping peak, which is centered in the MUC21 and MUC22 gene cluster upstream of the HLA-B and HLA-C genes. Journal of Allergy and Clinical Immunology 2014 134, 295-305DOI: (10.1016/j.jaci.2013.08.055) Copyright © 2014 Terms and Conditions

Fig 3 Forest plot of the meta-analysis of the effect of Native American ancestry on asthma in the Latino studies within the EVE Asthma Consortium. ORs and 95% CIs are listed next to each study. Journal of Allergy and Clinical Immunology 2014 134, 295-305DOI: (10.1016/j.jaci.2013.08.055) Copyright © 2014 Terms and Conditions

Fig 4 GWAS results. A, Manhattan plot of the GWAS showing a genome-wide significant peak at chromosome 17q21. B, LocusZoom plot of the 17q21 peak, which shows a broad area of linkage disequilibrium, with the most significant finding centered on the IKZF3 gene. Journal of Allergy and Clinical Immunology 2014 134, 295-305DOI: (10.1016/j.jaci.2013.08.055) Copyright © 2014 Terms and Conditions

Fig 5 Replication of previous genome-wide findings in the GALA II study. When provided, the original study’s effect estimate and CI are shown in red, whereas the effect estimate and CI in the present study are shown in teal. One study, including 3 SNPs reported only a summary P value.10 A second study, including 1 SNP, reported an OR but not a CI.49 Journal of Allergy and Clinical Immunology 2014 134, 295-305DOI: (10.1016/j.jaci.2013.08.055) Copyright © 2014 Terms and Conditions