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

<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 appr...

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Autores principales:	Giampaolo Ricci, Annalisa Astolfi, Daniel Remondini, Francesca Cipriani, Serena Formica, Arianna Dondi, Andrea Pession
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dcd38a2b336944d49e38f2179759a035
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spelling	oai:doaj.org-article:dcd38a2b336944d49e38f2179759a0352021-11-18T06:58:42ZPooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.1932-620310.1371/journal.pone.0016912https://doaj.org/article/dcd38a2b336944d49e38f2179759a0352011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21359210/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<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 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.<h4>Conclusion/significance</h4>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.Giampaolo RicciAnnalisa AstolfiDaniel RemondiniFrancesca CiprianiSerena FormicaArianna DondiAndrea PessionPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16912 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giampaolo Ricci Annalisa Astolfi Daniel Remondini Francesca Cipriani Serena Formica Arianna Dondi Andrea Pession Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.
description	<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 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.<h4>Conclusion/significance</h4>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.
format	article
author	Giampaolo Ricci Annalisa Astolfi Daniel Remondini Francesca Cipriani Serena Formica Arianna Dondi Andrea Pession
author_facet	Giampaolo Ricci Annalisa Astolfi Daniel Remondini Francesca Cipriani Serena Formica Arianna Dondi Andrea Pession
author_sort	Giampaolo Ricci
title	Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.
title_short	Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.
title_full	Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.
title_fullStr	Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.
title_full_unstemmed	Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.
title_sort	pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/dcd38a2b336944d49e38f2179759a035
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Pooled genome-wide analysis to identify novel risk loci for pediatric allergic asthma.

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