Variants near the HLA complex group 22 gene (HCG22) confer increased susceptibility to late-onset asthma in Japanese populations  Yohei Yatagai, MD, PhD, Tomomitsu Hirota, DDS, PhD, Tohru Sakamoto, MD, PhD, Hideyasu Yamada, MD, Hironori Masuko, MD, PhD, Yoshiko Kaneko, MD, PhD, Hiroaki Iijima, MD, PhD, Takashi Naito, MD, PhD, Emiko Noguchi, MD, PhD, Mayumi Tamari, MD, PhD, Michiaki Kubo, MD, PhD, Atsushi Takahashi, PhD, Satoshi Konno, MD, PhD, Hironi Makita, MD, PhD, Masaharu Nishimura, MD, PhD, Minako Hijikata, MD, PhD, Naoto Keicho, MD, PhD, Sakae Homma, MD, PhD, Yoshio Taguchi, MD, Arata Azuma, MD, PhD, Shoji Kudoh, MD, PhD, Nobuyuki Hizawa, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 138, Issue 1, Pages 281-283.e13 (July 2016) DOI: 10.1016/j.jaci.2015.11.023 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 ORs for association between rs2523870 and age of onset–specific subsets of asthma. By using 548 asthma cases and 1668 control subjects who had accurate information on age of onset of asthma in discovery sample 1 and the replication sample, the OR (95% CI) for association was plotted between rs2523870 and age of onset–specific subsets of asthma. The numbers of asthmatic patients who had the disease at the ages of 10 years or later, 20 years or later, 30 years or later, 40 years or later, 50 years or later, and 60 years or later were 457, 437, 379, 301, 238, and 153, respectively. ORs significantly greater than 1 are highlighted. *P < .005, **P < .001, and ***P < .0005. Journal of Allergy and Clinical Immunology 2016 138, 281-283.e13DOI: (10.1016/j.jaci.2015.11.023) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Flow chart of the study. Journal of Allergy and Clinical Immunology 2016 138, 281-283.e13DOI: (10.1016/j.jaci.2015.11.023) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Manhattan plots of the distribution of −log10 (P values) for association of 473,981 SNPs with susceptibility to late-onset asthma in the genome-wide meta-analysis. The x-axis represents the chromosomal position. Journal of Allergy and Clinical Immunology 2016 138, 281-283.e13DOI: (10.1016/j.jaci.2015.11.023) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Age of asthma onset according to the genotype at rs2523870. Using 548 patients with asthma in discovery sample 1 and the replication sample who had accurate information on age of asthma onset, we compared age of onset according to the genotype at rs2523870 using the Kruskal-Wallis test, which showed no significant differences among the 3 genotypes (P = .06). Journal of Allergy and Clinical Immunology 2016 138, 281-283.e13DOI: (10.1016/j.jaci.2015.11.023) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Location of rs2523870 and rs2517548 on chromosome 6p21.3. The positions of rs2523870 and rs2517548 on chromosome 6p21.3 based on GRCh38.p2 are 31,046,339 and 31,041,041 bp, respectively. The distances between these SNPs and the transcription initiation site (31,053,540 bp) of HCG22 are 7,201 and 12,499 bp for rs2523870 and rs2517548, respectively. Journal of Allergy and Clinical Immunology 2016 138, 281-283.e13DOI: (10.1016/j.jaci.2015.11.023) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Regional association plot and schematic diagram of linkage disequilibrium blocks in the mucin-like gene cluster region on chromosome 6p21.3. P values of the genotyped SNPs (red circles) and imputed SNPs (purple circles) are plotted against their physical position on chromosome 6 (NCBI36/hg18). Black triangles represent linkage disequilibrium blocks. Red, D′ ≥ 0.80; pink, 0.5 ≤ D′ < 0.8; blue, 0.2 ≤ D′ < 0.5; white, D′ < 0.2. Journal of Allergy and Clinical Immunology 2016 138, 281-283.e13DOI: (10.1016/j.jaci.2015.11.023) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 Fine plots of the distribution of −log10 (P values) for association of SNPs with HCG22 mRNA expression. rs2523870 and rs2517548 were closely located between HCG22 and MUC22 and showed strong associations with HCG22 mRNA expression (P = 8.54 × 10−87 and 3.23 × 10−84, respectively). Journal of Allergy and Clinical Immunology 2016 138, 281-283.e13DOI: (10.1016/j.jaci.2015.11.023) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions