Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases

• Published in: Journal of allergy and clinical immunology Vol. 130; no. 4; pp. 861 - 868.e7
• Main Authors: Li, Xingnan, Ampleford, Elizabeth J., Howard, Timothy D., Moore, Wendy C., Torgerson, Dara G., Li, Huashi, Busse, William W., Castro, Mario, Erzurum, Serpil C., Israel, Elliot, Nicolae, Dan L., Ober, Carole, Wenzel, Sally E., Hawkins, Gregory A., Bleecker, Eugene R., Meyers, Deborah A.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.2012; Elsevier; Elsevier Limited
• Subjects: alleles; Allergy and Immunology; Asthma; Asthma - etiology; Asthma - genetics; Asthma - immunology; Autoimmune diseases; Autoimmune Diseases - etiology; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; colitis; Crohn disease; Crohn's disease; Cytokines; Disease; DNA-Binding Proteins - genetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; genetics; Genome-Wide Association Study; Genomes; Histocompatibility antigen HLA; Humans; Immune system; Immunopathogenesis; Immunopathology; Inflammation; Inflammatory bowel disease; Interleukin 1; Interleukin 13; Interleukin 18 receptors; interleukin-18; lupus erythematosus; Medical sciences; Pneumology; Polymorphism, Single Nucleotide; Population; Psoriasis; Quality control; Research programs; Rheumatoid arthritis; risk; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; sclerosis; Single-nucleotide polymorphism; Studies; Systemic lupus erythematosus; Systemic sclerosis; Thymic stromal lymphopoietin; TNFAIP3 interacting protein 1; transcription factor NF-kappa B; Ulcerative colitis; Whites; TENOR; GSDMB; WDR36; GWAS; OR; TSLP; CAG; SARP; SLE; Asthma; IL18R; IL1RL1; genetics; SNP; TNIP1; CSGA; genome-wide association study; ORMDL3; LD; TNFAIP3 interacting protein 1; IL-1 receptor–like 1; Linkage disequilibrium; WD repeat domain 36; Systemic lupus erythematosus; ORM1-like 3; Chicago Asthma Genetics Study; Collaborative Studies on the Genetics of Asthma; IL-18 receptor 1; Severe Asthma Research Program; Thymic stromal lymphopoietin; The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens; Gasdermin B; Odds ratio; Single nucleotide polymorphism; Lung disease; Immunopathology; Respiratory disease; Autoimmune disease; Protein; Association; Immunology; Bronchus disease; Genetics; Obstructive pulmonary disease; Genome
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.04.041

Genome-wide association studies (GWASs) of asthma have consistently implicated the ORM1-like 3 and gasdermin B (ORMDL3-GSDMB), IL33, IL-1 receptor–like 1 and IL-18 receptor 1 (IL1RL1-IL18R1), RAD50-IL13, thymic stromal lymphopoietin and WD repeat domain 36 region (TSLP-WDR36), and HLA-DR/DQ regions. A GWAS of asthma was performed in a non-Hispanic white population. A GWAS was performed in 813 Severe Asthma Research Program/Collaborative Studies on the Genetics of Asthma/Chicago Asthma Genetics Study cases and 1564 control subjects. The GWAS results were compared with those of the published GWASs of autoimmune diseases. Multiple single nucleotide polymorphisms in the TNFAIP3 interacting protein 1 (TNIP1) gene, which interacts with TNFAIP3 and inhibits the TNF-α–induced nuclear factor κB inflammation pathway, were associated with asthma: rs1422673 (P = 3.44 × 10−7) and rs10036748 (P = 1.41 × 10−6, r2 = 0.67). rs1422673 was also associated with asthma in the published GABRIEL (P = .018) and EVE (P = 1.31 × 10−5) studies. The minor allele T of rs20541 in IL13 is the risk allele for asthma but the protective allele for psoriasis. The minor allele T of rs2395185 in HLA-DRA is the risk allele for asthma but the protective allele for ulcerative colitis. The minor allele A of rs2872507 in GSDMB is the protective allele for asthma but the risk allele for rheumatoid arthritis, Crohn disease, and ulcerative colitis. The T allele of rs10036748 in the TNIP1 gene is the minor protective allele for asthma but the minor or major risk allele for systemic lupus erythematosus and systemic sclerosis in non-Hispanic white or Chinese subjects, respectively. Our study suggests that single nucleotide polymorphisms associated with both asthma and autoimmune diseases might have opposite effects on immunopathogenesis.