title: Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.
abstract: BACKGROUND
  Genome-wide association studies of pooled DNA samples were shown to be a valuable tool to identify candidate SNPs associated to a phenotype. No such study was up to now applied to childhood allergic asthma, even if the very high complexity of asthma genetics is an appropriate field to explore the potential of pooled GWAS approach.
  
  
  RESULTS
  We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases comparing allergic children with and without asthma. We used a modular approach to identify the most significant loci associated with asthma by combining silhouette statistics and physical distance method with cluster-adapted thresholding. We found 97% concordance between pooled GWAS and individual genotyping, with 36 out of 37 top-scoring SNPs significant at individual genotyping level. The most significant SNP is located inside the coding sequence of C5, an already identified asthma susceptibility gene, while the other loci regulate functions that are relevant to bronchial physiopathology, as immune- or inflammation-mediated mechanisms and airway smooth muscle contraction. Integration with gene expression data showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models.
  
  
  CONCLUSIONS
  Combined silhouette statistics and cluster-adapted physical distance threshold analysis of pooled GWAS data is an efficient method to identify candidate SNP associated to asthma development in an allergic pediatric population.
authors.affiliation: Pediatric Unit, Department of Gynecologic, Obstetric and Pediatric Sciences, University of Bologna, Bologna, Italy. giampaolo.ricci@unibo.it
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Ricci
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.forename: Daniel
authors.initials: D
authors.lastname: Remondini
authors.forename: Francesca
authors.initials: F
authors.lastname: Cipriani
authors.forename: Serena
authors.initials: S
authors.lastname: Formica
authors.forename: Arianna
authors.initials: A
authors.lastname: Dondi
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001249:Asthma / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012107:Research Design; D012307:Risk Factors; D054928:Validation Studies as Topic