Association of variants in innate immune genes with asthma and eczema
Year: 2011
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema. In addition, we compare individual associations with those discovered using a multivariate approach. METHODS: Using a novel method, case control based association testing (C2BAT), 569 single nucleotide polymorphisms (SNPs) in 44 innate immune genes were tested for association with asthma and eczema in children from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. The screening algorithm was used to identify the top SNPs associated with asthma and eczema. We next investigated the interaction of innate immune variants with asthma and eczema risk using Bayesian networks. RESULTS: After correction for multiple comparisons, 7 SNPs in 6 genes (CARD25, TGFB1, LY96, ACAA1, DEFB1, and IFNG) were associated with asthma (adjusted p-value<0.02), while 5 SNPs in 3 different genes (CD80, STAT4, and IRAKI) were significantly associated with eczema (adjusted p-value < 0.02). None of these SNPs were associated with both asthma and eczema. Bayesian network analysis identified 4 SNPs that were predictive of asthma and 10 SNPs that predicted eczema. Of the genes identified using Bayesian networks, only CD80 was associated with eczema in the single-SNP study. Using novel methodology that allows for screening and replication in the same population, we have identified associations of innate immune genes with asthma and eczema. Bayesian network analysis suggests that additional SNPs influence disease susceptibility via SNP interactions. CONCLUSION: Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.
Source: Pediatric Allergy and Immunology
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: INTEGRATIVE GENOMICS APPROACHES TO MODEL THE GENETIC ARCHITECTURE OF ASTHMA, MARYLAND POPULATION RESEARCH CENTER, G2405186214, G2409943874, The Epidemiology of Home Allergens and Asthma, On the Genetic Determinants of Asthma and Obesity, The Epidemiology of Home Allergens and Asthma, Gene by Environment Interactions in Asthma and Allergy, G3858836152, GENE-ENVIRONMENT INTERACTIONS IN ASTHMA DEVELOPMENT, G4546641282, AN INTEGRATIVE GENOMICS APPROACH TO GENE BY ENVIRONMENT INTERACTIONS IN ASTHMA, G544826210, Perinatal Risk of Asthma in Infants of Asthmatic Mothers, INTEGRATIVE GENOMICS AND THE FETAL ORIGINS OF IMPAIRED LUNG FUNCTION, An Integrative Genomics Approach to Gene by Environment Interactions in Asthma
OpenAlex ID: W1912825302