No evidence of large genetic effects on steroid response in asthma patients Michael Mosteller, PhD, Louise Hosking, BSc, Kay Murphy, PhD, Judong Shen,

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No evidence of large genetic effects on steroid response in asthma patients Michael Mosteller, PhD, Louise Hosking, BSc, Kay Murphy, PhD, Judong Shen, PhD, Kijoung Song, PhD, Matthew Nelson, PhD, Soumitra Ghosh, PhD, MD Journal of Allergy and Clinical Immunology Volume 139, Issue 3, Pages 797-803.e7 (March 2017) DOI: 10.1016/j.jaci.2016.05.032 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Power curves for selected sample sizes showing the smallest per allele effect size detectable with 80% power as a function of MAF. N = 418 is the size of the largest published GWAS discovery sample set of ICS response in asthma to date; N = 1,787 is the size of the European ancestry subset of this current data set; N = 2,672 is the size of the full current data set; N = 25,000 is a representative choice for a large sample size. The dotted line approximates the size of a clinically meaningful allelic effect on FEV1 change (ie, 0.1 L for each copy of an allele, leading to a 0.2-L difference between homozygous genotypes). Journal of Allergy and Clinical Immunology 2017 139, 797-803.e7DOI: (10.1016/j.jaci.2016.05.032) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Manhattan plot summarizing association analyses between common (MAF ≥ 1%) genetic variants and ΔFEV1. ΔFEV1, Change from baseline in trough FEV1. The dotted black line indicates the prespecified criterion for statistically significant association (P = 1 × 10−8). Circular and triangular points represent imputed and directly genotyped variants, respectively. Journal of Allergy and Clinical Immunology 2017 139, 797-803.e7DOI: (10.1016/j.jaci.2016.05.032) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Comparison of 4 published ICS response association results (turquoise bars) with GSK results (red bars) in patients with asthma of European ancestry. ΔFEV1, Change from baseline in trough FEV1; GSK, GlaxoSmithKline. Effect size (beta) and 95% CIs for non-GSK results were estimated from reported means and SEs of the 3 genotypes. Journal of Allergy and Clinical Immunology 2017 139, 797-803.e7DOI: (10.1016/j.jaci.2016.05.032) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 QQ plot for the association between ΔFEV1 and common (MAF ≥ 1%) variants in 2672 patients with asthma. ΔFEV1, Change from baseline in trough FEV1. Journal of Allergy and Clinical Immunology 2017 139, 797-803.e7DOI: (10.1016/j.jaci.2016.05.032) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Manhattan plot summarizing association SKAT-O analysis between rare variants with ΔFEV1 in 1547 patients with asthma. P value thresholds 1 × 10−8 (significance threshold for common variants) and 3.24 × 10−6 (significance threshold for rare variants) are indicated by the black and red dashed lines, respectively. ΔFEV1, Change from baseline in trough FEV1; SKAT-O, sequence kernel association test. Journal of Allergy and Clinical Immunology 2017 139, 797-803.e7DOI: (10.1016/j.jaci.2016.05.032) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 QQ plot for the association SKAT-O analysis between rare variants with ΔFEV1 in 1547 patients with asthma. ΔFEV1, Change from baseline in trough FEV1; SKAT-O, sequence kernel association test. Journal of Allergy and Clinical Immunology 2017 139, 797-803.e7DOI: (10.1016/j.jaci.2016.05.032) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions