Functional variants of 17q12-21 are associated with allergic asthma but not allergic rhinitis Anand Kumar Andiappan, PhD, Yang Yie Sio, BSc, Bernett.

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Functional variants of 17q12-21 are associated with allergic asthma but not allergic rhinitis Anand Kumar Andiappan, PhD, Yang Yie Sio, BSc, Bernett Lee, PhD, Bani Kaur Suri, PhD, Sri Anusha Matta, BTech, Josephine Lum, BSc, Shihui Foo, BSc, Geraldine Koh, BSc, Jianjun Liu, PhD, Francesca Zolezzi, PhD, Michael Poidinger, PhD, De Yun Wang, MD, PhD, Olaf Rotzschke, PhD, Fook Tim Chew, PhD Journal of Allergy and Clinical Immunology Volume 137, Issue 3, Pages 758-766.e3 (March 2016) DOI: 10.1016/j.jaci.2015.08.038 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Chromosomal arrangement of genes in the 17q region with corresponding eQTL P values from whole-blood mRNA analysis of 71 Singapore Chinese subjects and linkage disequilibrium (LD) plots generated by using ArchiLD software. Journal of Allergy and Clinical Immunology 2016 137, 758-766.e3DOI: (10.1016/j.jaci.2015.08.038) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Effect of genetic polymorphisms on gene expression. A, Gene expression of 17q genes stratified by rs8076131 genotype with Padj values from the whole-blood eQTL cohort of 71 subjects described in Fig E1 (n = 39 for the AA genotype, n = 30 for the AG genotype, and n = 2 for the GG genotype). Padj values were calculated by adjusting for a number of genes tested in the chromosome 17q region. B, Schematic illustration showing the region of the ORMDL3 gene along with the location of SNPs and haplotype frequencies used for the in vitro luciferase assay. C, Relative luciferase units stratified by the haplotypes previously mentioned. The 2 common haplotypes (haplotype 1 at 0.6 and haplotype 2 at 0.3 frequencies) from HapMap CHB data were selected for the luciferase assay. Journal of Allergy and Clinical Immunology 2016 137, 758-766.e3DOI: (10.1016/j.jaci.2015.08.038) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Clinical relevance of the rs8076131 genotype. A, Total immunoglobulin levels detected in plasma in kilounits per liter from 180 subjects described in Fig E1. B, Percentage of eosinophils in whole blood stratified by rs8076131 alleles from 196 Singapore Chinese subjects (Fig E1). P values were estimated by using a nonparametric Mann-Whitney test, ∗P < .05 and ∗∗P < .01. Journal of Allergy and Clinical Immunology 2016 137, 758-766.e3DOI: (10.1016/j.jaci.2015.08.038) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Design of current study describing the various genetic association cohorts and functional association cohorts. Journal of Allergy and Clinical Immunology 2016 137, 758-766.e3DOI: (10.1016/j.jaci.2015.08.038) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Complete set of linked SNPs with reference to tag SNP rs8076131 at the chromosome 17q21 locus. This figure was generated with ArchiLD software by using a minor allele frequency of 0.05 and including singletons (http://archild.sign.a-star.edu.sg/; accessed March 28, 2015). Journal of Allergy and Clinical Immunology 2016 137, 758-766.e3DOI: (10.1016/j.jaci.2015.08.038) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions