title: Association of variants in innate immune genes with asthma and eczema.
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.
  
  
  CONCLUSIONS
  Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. sunita.sharma@channing.harvard.edu
authors.forename: Sunita
authors.initials: S
authors.lastname: Sharma
authors.forename: Audrey
authors.initials: A
authors.lastname: Poon
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Himes
authors.forename: Jessica
authors.initials: J
authors.lastname: Lasky-Su
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Sordillo
authors.forename: Kathleen
authors.initials: K
authors.lastname: Belanger
authors.forename: Donald K
authors.initials: DK
authors.lastname: Milton
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bracken
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Triche
authors.forename: Brian P
authors.initials: BP
authors.lastname: Leaderer
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
mesh_terms: D000465:Algorithms; D001249:Asthma / Q000235:genetics*; D001499:Bayes Theorem; D002675:Child, Preschool; D004485:Eczema / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide