Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients Xingnan Li, PhD, MS, Gregory A. Hawkins,

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Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients Xingnan Li, PhD, MS, Gregory A. Hawkins, PhD, Elizabeth J. Ampleford, PhD, Wendy C. Moore, MD, Huashi Li, MS, Annette T. Hastie, PhD, Timothy D. Howard, PhD, Homer A. Boushey, MD, William W. Busse, MD, William J. Calhoun, MD, Mario Castro, MD, Serpil C. Erzurum, MD, Elliot Israel, MD, Robert F. Lemanske, MD, Stanley J. Szefler, MD, Stephen I. Wasserman, MD, Sally E. Wenzel, MD, Stephen P. Peters, MD, PhD, Deborah A. Meyers, PhD, Eugene R. Bleecker, MD Journal of Allergy and Clinical Immunology Volume 132, Issue 2, Pages 313-320.e15 (August 2013) DOI: 10.1016/j.jaci.2013.01.051 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Genome-wide association of ppFEV1 values with 369,771 SNPs in 4 European American populations. The color scale of the x-axis represents chromosomes. Negative log-transformed meta-analysis P values are shown on the y-axis. The blue horizontal line is drawn at a P value of 10−4. Journal of Allergy and Clinical Immunology 2013 132, 313-320.e15DOI: (10.1016/j.jaci.2013.01.051) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Joint analysis of 4 TH1 pathway SNPs in IL12A, IL12RB1, STAT4, and IRF2 for ppFEV1 values in the SARP population. Blue bars represent ppFEV1, and purple bars represent percentages of subjects with severe asthma based on ATS classification. Journal of Allergy and Clinical Immunology 2013 132, 313-320.e15DOI: (10.1016/j.jaci.2013.01.051) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Two-step asthma progression genetic model. The red arrow indicates higher gene expression levels or protein activities. The green arrow indicates lower gene expression levels or protein activities. The question mark indicates the lack of available experimental evidence. Journal of Allergy and Clinical Immunology 2013 132, 313-320.e15DOI: (10.1016/j.jaci.2013.01.051) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 QQ plot of genome-wide association of ppFEV1 values with 369,771 SNPs in 4 European American populations. Negative log-transformed expected P values are shown on the x-axis. Negative log-transformed observed P values are shown on the y-axis. Journal of Allergy and Clinical Immunology 2013 132, 313-320.e15DOI: (10.1016/j.jaci.2013.01.051) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Association plot of the IL12A region. Negative log-transformed P value (left) and recombination rate (right) are shown. The red color scale represents the strength of LD of the SNPs with rs7636840. Journal of Allergy and Clinical Immunology 2013 132, 313-320.e15DOI: (10.1016/j.jaci.2013.01.051) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Association plot of the IL12RB1 region. Negative log-transformed P value (left) and recombination rate (right) are shown. The red color scale represents the strength of LD of the SNPs with rs388159. Journal of Allergy and Clinical Immunology 2013 132, 313-320.e15DOI: (10.1016/j.jaci.2013.01.051) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Association plot of the STAT4 region. Negative log-transformed P value (left) and recombination rate (right) are shown. The red color scale represents the strength of LD of the SNPs with rs925847. Journal of Allergy and Clinical Immunology 2013 132, 313-320.e15DOI: (10.1016/j.jaci.2013.01.051) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Association plot of the IRF2 region. Negative log-transformed P value (left) and recombination rate (right) are shown. The red color scale represents the strength of LD of the SNPs with rs3756089. Journal of Allergy and Clinical Immunology 2013 132, 313-320.e15DOI: (10.1016/j.jaci.2013.01.051) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions