Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids Heung-Woo Park, MD, PhD, Amber Dahlin, PhD,

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Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids Heung-Woo Park, MD, PhD, Amber Dahlin, PhD, MMSc, Szeman Tse, MDCM, MPH, Qing Ling Duan, PhD, Brooke Schuemann, BS, Fernando D. Martinez, MD, Stephen P. Peters, MD, PhD, Stanley J. Szefler, MD, John J. Lima, PharmD, Michiaki Kubo, MD, PhD, Mayumi Tamari, MD, PhD, Kelan G. Tantisira, MD, MPH Journal of Allergy and Clinical Immunology Volume 133, Issue 3, Pages 664-669.e5 (March 2014) DOI: 10.1016/j.jaci.2013.12.1042 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Changes in asthma symptom scores after ICS treatment in the 2 pediatric asthma populations (CAMP and CARE) genotyped for rs10044254 and stratified by genotype status. Subjects in the CAMP and CARE trials who carried 2 variant alleles showed increases in asthma symptom scores after ICS treatment, whereas subjects that were homozygous for the reference allele and heterozygous showed decreases. Data represent medians (IQRs), and small circles represent subjects who were outliers from the first and the third quartiles. Journal of Allergy and Clinical Immunology 2014 133, 664-669.e5DOI: (10.1016/j.jaci.2013.12.1042) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 FBXL7 gene expression in response to dexamethasone stimulation in immortalized B cells of the CAMP subject stratified by rs10044254 genotype. Reference represents expression data of B cells from the subjects with the reference allele, and Variant indicates expression data of B cells from the subjects with the variant allele (allelic model). Data represent medians (IQRs), and small circles represent subjects who were outliers from the first and the third quartiles. Journal of Allergy and Clinical Immunology 2014 133, 664-669.e5DOI: (10.1016/j.jaci.2013.12.1042) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 GWAS quantile-quantile plot of 124 CAMP subjects. A, Dominant model. B, Recessive model. 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 2014 133, 664-669.e5DOI: (10.1016/j.jaci.2013.12.1042) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Changes in asthma symptom scores after ICS treatment in the 2 pediatric asthma populations (CAMP and CARE) genotyped for rs1558726 and rs2388639 stratified by genotype status. A, rs1558726. B, rs2388639. Data represent medians (IQRs), and small circles represent subjects who were outliers from the first and the third quartiles. Journal of Allergy and Clinical Immunology 2014 133, 664-669.e5DOI: (10.1016/j.jaci.2013.12.1042) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Analysis of the potential pathway interactions between the FBXL7 and HIF1A genes through GeneMania (www.genemania.org). The FBXL7 gene is coexpressed with HIF1A, which is directly or indirectly predicted to interact with HIF-1α. Journal of Allergy and Clinical Immunology 2014 133, 664-669.e5DOI: (10.1016/j.jaci.2013.12.1042) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions