117 Allergy is an Epithelial Barrier Disease

search Institute, Cleveland, OH; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA; Department of Pediatrics, University of Virginia Health Systems, Charlottesville, VA; Brigham & Women’s Hospital, Harvard University, Boston, MA; Departments of Medicine and Public Health Sciences, University of Wisconsin Hospitals and Clinics, Madison, WI; Medicine, University of Pittsburgh, Pittsburgh, PA. Background: Genome-wide association studies (GWAS) of asthma and asthma-related traits, including our previous TENOR study, have consistently identified ORMDL3-GSDMB, IL33, IL1RL1-IL18R1, RAD50-IL13, TSLP-WDR36, and HLA-DR/DQ regions. Methods: In this study, GWAS of asthma was performed in non-Hispanic white population from STAMPEED study (813 cases and 1564 controls). Our GWAS results were compared with the published GWAS of asthma and autoimmune diseases (AD). Results: Multiple SNPs in TNFAIP3 interacting protein 1 (TNIP1) on chromosome 5q32-q33.1 were associated with asthma in STAMPEED: rs1422673 (P1⁄4 3.44 · 1027) and rs10036748 (P 1⁄4 1.41 · 1026). rs1422673 was weakly associated with asthma in the published GABRIEL study (P 1⁄4 0.018 for meta-analysis) but not in the TENOR study (P 1⁄4 0.18 but same trend). TNIP1 may interact with TNFAIP3 and inhibit TNFa-induced NFkB inflammation pathway. Joint analyses were performed on 6 SNPs in GSDMB (rs2872507), IL33 (rs3939286), IL1RL1 (rs13431828), IL13 (rs20541), TSLP (rs1837253), and HLA-DRA (rs2395185) in STAMPEED and TENOR populations, but only limited variance can be explained (percentage of deviance1⁄4 1.5–1.9%; the area under the receiver operating characteristic curve (AUC) 1⁄4 0.58–0.59). Minor allele T of rs20541 in IL13 is the risk allele for asthma but the protective allele for psoriasis. Minor allele A of rs2872507 in GSDMB is the protective allele for asthma but the risk allele for rheumatoid arthritis, Crohn’s disease and ulcerative colitis. T allele of rs10036748 in TNIP1 is the minor protective allele for asthma, but the minor or major risk allele for systemic lupus erythematosus in nonHispanic white or Chinese population, respectively. Conclusions: Our study provides genetic evidence that asthma and AD have opposite immunopathogenesis directions.