Genome-wide association study reveals class I MHC–restricted T cell–associated molecule gene (CRTAM) variants interact with vitamin D levels to affect.

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Genome-wide association study reveals class I MHC–restricted T cell–associated molecule gene (CRTAM) variants interact with vitamin D levels to affect asthma exacerbations Rose Du, MD, PhD, Augusto A. Litonjua, MD, Kelan G. Tantisira, MD, Jessica Lasky-Su, ScD, Shamil R. Sunyaev, PhD, Barbara J. Klanderman, PhD, Juan C. Celedón, MD, DrPH, Lydiana Avila, MD, Manuel E. Soto-Quiros, MD, PhD, Scott T. Weiss, MD Journal of Allergy and Clinical Immunology Volume 129, Issue 2, Pages 368-373.e5 (February 2012) DOI: 10.1016/j.jaci.2011.09.034 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Association of CRTAM genotype with rates of asthma exacerbation as stratified by high (>30 ng/mL) versus low (≤30 ng/mL) vitamin D levels in the CAMP and Costa Rican studies. Error bars indicate SEs. In the CAMP analysis exacerbation rates are over the first year of the trial, whereas in the Costa Rican analysis exacerbation rates are over the past year before entry into the study. Zero, 1, and 2 are the genotypes AA, Aa, and aa, respectively, where a is the minor allele. Interaction P values for the CAMP study are .00536, .00175, and .00638 for rs7941607, rs2272094, and rs2140151, respectively. For the Costa Rican study, the interaction P values are .00990, .02544, and .02932 for rs7941607, rs2272094, and rs2140151, respectively. The number of subjects in each group is indicated in the figure. Journal of Allergy and Clinical Immunology 2012 129, 368-373.e5DOI: (10.1016/j.jaci.2011.09.034) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 ORs for asthma exacerbation in subjects with low vitamin D levels compared with those in subjects with high vitamin D levels. Blue, Mantel-Haenszel summary OR of both the CAMP and Costa Rican populations. The number of subjects with genotypes 0, 1, and 2 are 203, 163, and 29 for the CAMP cohort and 261, 260, and 52 for the Costa Rican cohort, respectively. Journal of Allergy and Clinical Immunology 2012 129, 368-373.e5DOI: (10.1016/j.jaci.2011.09.034) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 CRTAM-normalized expression for cell lines homozygous in the major (Wildtype, GG, n = 10) and minor (mutant, AA, n = 10) alleles for rs2272094 in the presence and absence of vitamin D. Ten cell lines were used in each of the 4 groups. Error bars indicate SEs. Journal of Allergy and Clinical Immunology 2012 129, 368-373.e5DOI: (10.1016/j.jaci.2011.09.034) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Manhattan plots of interaction P values for population-based (A) and family-based (B) approaches for the CAMP cohort. SNPs replicated in the Costa Rican cohort are labeled orange, and CRTAM SNPs are labeled green. Journal of Allergy and Clinical Immunology 2012 129, 368-373.e5DOI: (10.1016/j.jaci.2011.09.034) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Linkage disequilibrium among the CRTAM SNPs in the CAMP and Costa Rican cohorts. The values in the boxes are r2 × 100. The pattern of linkage disequilibrium is very similar in the CAMP and Costa Rican cohorts. Journal of Allergy and Clinical Immunology 2012 129, 368-373.e5DOI: (10.1016/j.jaci.2011.09.034) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Flanking sequence for rs2272094. The splice site, binding sequence for steroidogenic factor 1 (SF-1), and TTS are shown. Journal of Allergy and Clinical Immunology 2012 129, 368-373.e5DOI: (10.1016/j.jaci.2011.09.034) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions