Genetic risk factors for decreased bone mineral accretion in children with asthma receiving multiple oral corticosteroid bursts Heung-Woo Park, MD, PhD,

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Genetic risk factors for decreased bone mineral accretion in children with asthma receiving multiple oral corticosteroid bursts Heung-Woo Park, MD, PhD, Bing Ge, MSc, Szeman Tse, MDCM, Elin Grundberg, PhD, Tomi Pastinen, MD, PhD, H. William Kelly, PharmD, Kelan G. Tantisira, MD, MPH Journal of Allergy and Clinical Immunology Volume 136, Issue 5, Pages 1240-1246.e8 (November 2015) DOI: 10.1016/j.jaci.2015.04.014 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Position of identified SNPs and genes on chromosome 17q. A, Rs9896933, rs2074439, TCBD, and TUBG1. B, LD plot between rs9896933 and rs3785522 (HapMap CEPH population). C, Analysis of potential pathway interactions between TBCD and TUBG1 through GeneMania (www.genemania.org). Journal of Allergy and Clinical Immunology 2015 136, 1240-1246.e8DOI: (10.1016/j.jaci.2015.04.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Correlations between cumulative dose of OCS and BMA stratified by the number of mutant alleles of rs9896933 and rs2074439. Regression lines of the whole population, subjects without any mutant alleles, subjects with 1 mutant allele, subjects with 2 mutant alleles, and subjects with 3 mutant alleles are shown. The slope obtained from simple linear regression analysis becomes steeper as the number of mutant alleles of the 2 SNPs increases. P values were obtained from Pearson correlation analysis. Journal of Allergy and Clinical Immunology 2015 136, 1240-1246.e8DOI: (10.1016/j.jaci.2015.04.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Quantile-quantile and Manhattan plots for interaction results. A, Quantile-quantile plot. Red line, Genome-wide significance. B, Manhattan plot. Journal of Allergy and Clinical Immunology 2015 136, 1240-1246.e8DOI: (10.1016/j.jaci.2015.04.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Correlations between cumulative dose of OCS and BMA stratified by genotype of rs9896933. A, Whole population, reference allele homozygotes, heterozygotes, and mutant allele homozygotes. B, Merge of individual regression lines. A slope obtained from simple linear regression analysis became steeper as the number of mutant alleles of the 2 SNPs increased. P values were obtained from Pearson correlation analysis. Journal of Allergy and Clinical Immunology 2015 136, 1240-1246.e8DOI: (10.1016/j.jaci.2015.04.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Correlations between cumulative dose of OCS and BMA stratified by genotype of rs2074439. A, Whole population, reference allele homozygotes, heterozygotes, and mutant allele homozygotes. B, Merge of individual regression lines. A slope obtained from simple linear regression analysis became steeper as the number of mutant alleles of the 2 SNPs increased. P values were obtained from Pearson correlation analysis. Journal of Allergy and Clinical Immunology 2015 136, 1240-1246.e8DOI: (10.1016/j.jaci.2015.04.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Correlations between cumulative dose of OCS and BMA stratified by number of mutant alleles of rs9896933 and rs2074439 (merge of individual regression lines). A slope obtained from simple linear regression analysis became steeper as the number of mutant alleles of the 2 SNPs increased. P values were obtained from Pearson correlation analysis. Journal of Allergy and Clinical Immunology 2015 136, 1240-1246.e8DOI: (10.1016/j.jaci.2015.04.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Comparison of BMA stratified by rs9896933 in asthmatic children without OCS bursts between those randomized to ICS and those randomized to placebo. Differences according to the treatment groups or genotypes of rs9896933 were not statistically significant. Journal of Allergy and Clinical Immunology 2015 136, 1240-1246.e8DOI: (10.1016/j.jaci.2015.04.014) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions