Unknown,Transcriptomics,Genomics,Proteomics

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Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma

ABSTRACT: 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 (from mouse experimental asthma model taken from GSE6858 and GSE1301) showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models. Affymetrix SNP arrays (Mapping 250K NspI and StyI) were performed according to the manufacturer's directions on pooled DNA extracted from peripheral blood samples.The design is a pooled-GWAS. DNA samples were assigned to the Asthma group if displaying symptoms of asthma, alone or associated to other allergic phenotypes, including rhinoconjunctivitis (RC), and assigned to the RC group if displaying rhinitis or rhinoconjunctivits alone or associated to other allergic phenotypes, excluding asthma. Each of the two groups was subdiveded into 4 independent groups of samples, each containing 31-36 individuals. Individual DNA samples were then added to their respective pools in equivalent molar amounts. Each pool was labeled and hybridized independently on three different arrays (3 technical replicates for each pool).

ORGANISM(S): Homo sapiens

SUBMITTER: Giampaolo Ricci

PROVIDER: E-GEOD-24481 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.

Ricci Giampaolo G Astolfi Annalisa A Remondini Daniel D Cipriani Francesca F Formica Serena S Dondi Arianna A Pession Andrea A

PloS one 20110216 2

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases compar ...[more]

PMID: 21359210

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Dataset Information

Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma

Publications

Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.

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