Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans Rachel A. Myers, PhD, Blanca E. Himes,

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Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans Rachel A. Myers, PhD, Blanca E. Himes, PhD, Christopher R. Gignoux, MS, James J. Yang, PhD, W. James Gauderman, PhD, Cristina Rebordosa, MD, Jianming Xie, PhD, Dara G. Torgerson, PhD, Albert M. Levin, PhD, James Baurley, PhD, Penelope E. Graves, ScD, Rasika A. Mathias, ScD, Isabelle Romieu, MD, ScD, Lindsey A. Roth, MA, David Conti, PhD, Lydiana Avila, MD, Celeste Eng, BS, Hita Vora, MS, Michael A. LeNoir, MD, Manuel Soto-Quiros, MD, PhD, Jinghua Liu, PhD, Juan C. Celedón, MD, DrPH, Harold J. Farber, MD, MSPH, Rajesh Kumar, MD, MS, Pedro C. Avila, MD, Kelley Meade, MD, Denise Serebrisky, MD, Shannon Thyne, MD, William Rodriguez-Cintron, MD, Jose R. Rodriguez-Santana, MD, Luisa N. Borrell, DDS, PhD, Robert F. Lemanske, MD, Eugene R. Bleecker, MD, Deborah A. Meyers, PhD, Stephanie J. London, MD, PhD, Kathleen C. Barnes, PhD, Benjamin A. Raby, MD, Fernando D. Martinez, MD, Frank D. Gilliland, MD, PhD, L. Keoki Williams, MD, MPH, Esteban G. Burchard, MD, MPH, Scott T. Weiss, MD, Dan L. Nicolae, PhD, Carole Ober, PhD Journal of Allergy and Clinical Immunology Volume 130, Issue 6, Pages 1294-1301 (December 2012) DOI: 10.1016/j.jaci.2012.07.054 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Q-Q plots of the replication results. In each plot (A-D) the observed log(P value) is plotted against the expected log(P value). A, One hundred twenty-eight SNPs selected for replication in European Americans, B, 340 SNPs selected for replication in the African Americans, C, 258 SNPs selected for replication in the Latinos, and D, 2450 SNPs selected for replication in all samples. See the Methods section for details on SNP selection. Journal of Allergy and Clinical Immunology 2012 130, 1294-1301DOI: (10.1016/j.jaci.2012.07.054) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Results for rs1061477 in the KLK3 gene. A, Forest plot showing the ORs and 95% CIs for all European American studies in the primary and replication meta-analyses. Two European American studies included in the primary analysis (CARE and CAMP) were family-based studies and did not report odds ratios; those studies are not included in the figure. The R package meta was used for determining the combined OR and rmeta was used to generate the plot. B, Regional plot of the European American association P values surrounding rs1061477. Diamond represents P values for SNPs from the primary study, and circles represent the combined (primary + replication) P values. SNPs are shaded according to LD with the SNP rs1061477, red indicating high LD. The light blue line represents CEU 1000 genomes pilot recombination rates. This figure was generated with SNAP.35,36 CARE, Childhood Asthma Research and Education; CHS, Children’s Health Study; COAST, Childhood Origins of Asthma; iCAP, The i2b2 Crimson Asthma Project; STAMPEED, SNP Typing for Association with Multiple Phenotypes from Existing Epidemiologic Data. Journal of Allergy and Clinical Immunology 2012 130, 1294-1301DOI: (10.1016/j.jaci.2012.07.054) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Results for rs9570077 on 13q21. A, Forest plot showing the ORs and 95% CIs for all European American studies in the primary and replication meta-analyses. Two European American studies included in the primary analysis (CARE and CAMP) were family-based studies and did not report ORs; those studies are not included in the figure. The R package meta was used for determining the combined OR and rmeta was used to generate the plot. B, Regional plot of the European American association P values surrounding rs9570077. Diamond represents P values for SNPs from the primary study, and circles represent the combined (primary + replication) P values. SNPs are shaded according to LD with the SNP rs9570077, red indicating high LD. The light blue line represents CEU 1000 genomes pilot recombination rates. This figure was generated with SNAP.35,36 CARE, Childhood Asthma Research and Education; CHS, Children’s Health Study; COAST, Childhood Origins of Asthma; iCAP, The i2b2 Crimson Asthma Project; STAMPEED, SNP Typing for Association with Multiple Phenotypes from Existing Epidemiologic Data. Journal of Allergy and Clinical Immunology 2012 130, 1294-1301DOI: (10.1016/j.jaci.2012.07.054) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Forest plot of rs9891949 near AURKB. The ORs and 95% CIs for all European American studies in the primary and replication meta-analyses. Two European American studies included in the primary analysis (CARE and CAMP) were family-based studies and did not report odds ratios; those studies are not included in the figure. CARE, Childhood Asthma Research and Education; CHS, Children’s Health Study; COAST, Childhood Origins of Asthma; iCAP, The i2b2 Crimson Asthma Project; STAMPEED, SNP Typing for Association with Multiple Phenotypes from Existing Epidemiologic Data. Journal of Allergy and Clinical Immunology 2012 130, 1294-1301DOI: (10.1016/j.jaci.2012.07.054) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Journal of Allergy and Clinical Immunology 2012 130, 1294-1301DOI: (10.1016/j.jaci.2012.07.054) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions