Inhaled corticosteroid treatment modulates ZNF432 gene variant’s effect on bronchodilator response in asthmatics Ann Chen Wu, MD, MPH, Blanca E. Himes,

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Inhaled corticosteroid treatment modulates ZNF432 gene variant’s effect on bronchodilator response in asthmatics Ann Chen Wu, MD, MPH, Blanca E. Himes, PhD, Jessica Lasky-Su, PhD, Augusto Litonjua, MD, MPH, Stephen P. Peters, MD, PhD, John Lima, PharmD, Michiaki Kubo, MD, PhD, Mayumi Tamari, MD, PhD, Yusuke Nakamura, MD, PhD, Weiliang Qiu, PhD, Scott T. Weiss, MD, MS, Kelan Tantisira, MD, MPH Journal of Allergy and Clinical Immunology Volume 133, Issue 3, Pages 723-728.e3 (March 2014) DOI: 10.1016/j.jaci.2013.09.037 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Manhattan plot of −log10 (P value) for the analysis in CAMP, demonstrating that multiple SNPs in chromosome 19 may be associated with BDR and modulated by ICS treatment. Journal of Allergy and Clinical Immunology 2014 133, 723-728.e3DOI: (10.1016/j.jaci.2013.09.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Depiction of the effect of treatment with ICS vs no ICS and genotype on the outcome of BDR for rs3752120. The x-axis shows the number of genotypes. There are 3 possibilities for the number of copies of rs3752120: 0 copy, 1 copy, or 2 copies. The y-axis shows the BDR. This figure demonstrates that having 2 copies of the mutant allele and not being treated with ICS produces a higher BDR than having 2 mutant alleles and being treated with ICS. A, CAMP population. B, LOCCS population. Journal of Allergy and Clinical Immunology 2014 133, 723-728.e3DOI: (10.1016/j.jaci.2013.09.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 The region of association near rs10411428 to BDR while modulated by treatment with ICS. The x-axis denotes the position along the chromosome 19. The y-axis denotes −log10 (P), which corresponds to 1000GP imputed data P values between the SNP, rs10411428, to each SNP in the plot is denoted in colors and was computed according to 1000GP June 2010 CEU data. The plot was created by using LocusZoom (see Pruim et al22). Journal of Allergy and Clinical Immunology 2014 133, 723-728.e3DOI: (10.1016/j.jaci.2013.09.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Quantile-quantile plot in CAMP, demonstrating that the SNPs with the lowest P values deviate from what is expected for a null distribution, which suggests that some may reflect true associations with BDR that are modulated by exposure to ICS. Journal of Allergy and Clinical Immunology 2014 133, 723-728.e3DOI: (10.1016/j.jaci.2013.09.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Box plot of genotype vs expression levels for rs11666341. Cells from subjects homozygous for the major allele rs11666341 had lower expression levels under dexamethasone-treated conditions, P = .046. A, Major allele; G, minor allele. Journal of Allergy and Clinical Immunology 2014 133, 723-728.e3DOI: (10.1016/j.jaci.2013.09.037) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions