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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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

Ricci G., Astolfi A., Remondini D., Cipriani F., Formica S., Dondi A., et al. (2011). Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma. PLOS ONE, 6, 1-9 [10.1371/journal.pone.0016912].

Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma

RICCI, GIAMPAOLO;ASTOLFI, ANNALISA;REMONDINI, DANIEL;CIPRIANI, FRANCESCA;FORMICA, SERENA;DONDI, ARIANNA;PESSION, ANDREA
2011

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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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
2011
Ricci G., Astolfi A., Remondini D., Cipriani F., Formica S., Dondi A., et al. (2011). Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma. PLOS ONE, 6, 1-9 [10.1371/journal.pone.0016912].
Ricci G.; Astolfi A.; Remondini D.; Cipriani F.; Formica S.; Dondi A.; Pession A.
File in questo prodotto:
File Dimensione Formato  
journal.pone.0016912.PDF

accesso aperto

Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 515.25 kB
Formato Adobe PDF
515.25 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/99931
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 16
social impact