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Meta-analysis of genome-wide linkage studies of asthma and related traits

BACKGROUND: Asthma and allergy are complex multifactorial disorders, with both genetic and environmental components determining disease expression. The use of molecular genetics holds great promise for the identification of novel drug targets for the treatment of asthma and allergy. Genome-wide link...

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Autores principales: Denham, Samuel, Koppelman, Gerard H, Blakey, John, Wjst, Matthias, Ferreira, Manuel A, Hall, Ian P, Sayers, Ian
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391165/
https://www.ncbi.nlm.nih.gov/pubmed/18442398
http://dx.doi.org/10.1186/1465-9921-9-38
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author Denham, Samuel
Koppelman, Gerard H
Blakey, John
Wjst, Matthias
Ferreira, Manuel A
Hall, Ian P
Sayers, Ian
author_facet Denham, Samuel
Koppelman, Gerard H
Blakey, John
Wjst, Matthias
Ferreira, Manuel A
Hall, Ian P
Sayers, Ian
author_sort Denham, Samuel
collection PubMed
description BACKGROUND: Asthma and allergy are complex multifactorial disorders, with both genetic and environmental components determining disease expression. The use of molecular genetics holds great promise for the identification of novel drug targets for the treatment of asthma and allergy. Genome-wide linkage studies have identified a number of potential disease susceptibility loci but replication remains inconsistent. The aim of the current study was to complete a meta-analysis of data from genome-wide linkage studies of asthma and related phenotypes and provide inferences about the consistency of results and to identify novel regions for future gene discovery. METHODS: The rank based genome-scan meta-analysis (GSMA) method was used to combine linkage data for asthma and related traits; bronchial hyper-responsiveness (BHR), allergen positive skin prick test (SPT) and total serum Immunoglobulin E (IgE) from nine Caucasian asthma populations. RESULTS: Significant evidence for susceptibility loci was identified for quantitative traits including; BHR (989 pedigrees, n = 4,294) 2p12-q22.1, 6p22.3-p21.1 and 11q24.1-qter, allergen SPT (1,093 pedigrees, n = 4,746) 3p22.1-q22.1, 17p12-q24.3 and total IgE (729 pedigrees, n = 3,224) 5q11.2-q14.3 and 6pter-p22.3. Analysis of the asthma phenotype (1,267 pedigrees, n = 5,832) did not identify any region showing genome-wide significance. CONCLUSION: This study represents the first linkage meta-analysis to determine the relative contribution of chromosomal regions to the risk of developing asthma and atopy. Several significant results were obtained for quantitative traits but not for asthma confirming the increased phenotype and genetic heterogeneity in asthma. These analyses support the contribution of regions that contain previously identified asthma susceptibility genes and provide the first evidence for susceptibility loci on 5q11.2-q14.3 and 11q24.1-qter.
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spelling pubmed-23911652008-05-22 Meta-analysis of genome-wide linkage studies of asthma and related traits Denham, Samuel Koppelman, Gerard H Blakey, John Wjst, Matthias Ferreira, Manuel A Hall, Ian P Sayers, Ian Respir Res Research BACKGROUND: Asthma and allergy are complex multifactorial disorders, with both genetic and environmental components determining disease expression. The use of molecular genetics holds great promise for the identification of novel drug targets for the treatment of asthma and allergy. Genome-wide linkage studies have identified a number of potential disease susceptibility loci but replication remains inconsistent. The aim of the current study was to complete a meta-analysis of data from genome-wide linkage studies of asthma and related phenotypes and provide inferences about the consistency of results and to identify novel regions for future gene discovery. METHODS: The rank based genome-scan meta-analysis (GSMA) method was used to combine linkage data for asthma and related traits; bronchial hyper-responsiveness (BHR), allergen positive skin prick test (SPT) and total serum Immunoglobulin E (IgE) from nine Caucasian asthma populations. RESULTS: Significant evidence for susceptibility loci was identified for quantitative traits including; BHR (989 pedigrees, n = 4,294) 2p12-q22.1, 6p22.3-p21.1 and 11q24.1-qter, allergen SPT (1,093 pedigrees, n = 4,746) 3p22.1-q22.1, 17p12-q24.3 and total IgE (729 pedigrees, n = 3,224) 5q11.2-q14.3 and 6pter-p22.3. Analysis of the asthma phenotype (1,267 pedigrees, n = 5,832) did not identify any region showing genome-wide significance. CONCLUSION: This study represents the first linkage meta-analysis to determine the relative contribution of chromosomal regions to the risk of developing asthma and atopy. Several significant results were obtained for quantitative traits but not for asthma confirming the increased phenotype and genetic heterogeneity in asthma. These analyses support the contribution of regions that contain previously identified asthma susceptibility genes and provide the first evidence for susceptibility loci on 5q11.2-q14.3 and 11q24.1-qter. BioMed Central 2008 2008-04-28 /pmc/articles/PMC2391165/ /pubmed/18442398 http://dx.doi.org/10.1186/1465-9921-9-38 Text en Copyright © 2008 Denham et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Denham, Samuel
Koppelman, Gerard H
Blakey, John
Wjst, Matthias
Ferreira, Manuel A
Hall, Ian P
Sayers, Ian
Meta-analysis of genome-wide linkage studies of asthma and related traits
title Meta-analysis of genome-wide linkage studies of asthma and related traits
title_full Meta-analysis of genome-wide linkage studies of asthma and related traits
title_fullStr Meta-analysis of genome-wide linkage studies of asthma and related traits
title_full_unstemmed Meta-analysis of genome-wide linkage studies of asthma and related traits
title_short Meta-analysis of genome-wide linkage studies of asthma and related traits
title_sort meta-analysis of genome-wide linkage studies of asthma and related traits
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391165/
https://www.ncbi.nlm.nih.gov/pubmed/18442398
http://dx.doi.org/10.1186/1465-9921-9-38
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