Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)
Identifieur interne : 001417 ( Istex/Corpus ); précédent : 001416; suivant : 001418Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)
Auteurs : F. Castro-Giner ; R. De Cid ; J R Gonzalez ; D. Jarvis ; J. Heinrich ; C. Janson ; E R Omenaas ; M C Matheson ; I. Pin ; J M Ant ; M. Wjst ; X. Estivill ; M. KogevinasSource :
- Thorax [ 0040-6376 ] ; 2010-02.
English descriptors
- KwdEn :
- Allergy, Asthma, Asthma susceptibility gene, Atopic, Atopic asthma, Atopy, Barcelona, Body mass index, Bonferroni, Bonferroni correction, Candidate genes, Chromosome, Clin, Cohort, Comparison group, Ecrhs, European community, Gene, Genet, Gure, Haplotype, Health survey, High serum, Locus, Npsr1, Npsr1 gene, Npsr1 polymorphisms, Npsr1 snps, Odds ratios, Online, Online supplement, Onset asthma, Other studies, Persistent asthma, Phenotype, Polymorphism, Positional, Receptor, Respir, Respir crit care, Single nucleotide polymorphisms, Smoking status, Snp, Susceptibility, Thorax.
- Teeft :
- Allergy, Asthma, Asthma susceptibility gene, Atopic, Atopic asthma, Atopy, Barcelona, Body mass index, Bonferroni, Bonferroni correction, Candidate genes, Chromosome, Clin, Cohort, Comparison group, Ecrhs, European community, Gene, Genet, Gure, Haplotype, Health survey, High serum, Locus, Npsr1, Npsr1 gene, Npsr1 polymorphisms, Npsr1 snps, Odds ratios, Online, Online supplement, Onset asthma, Other studies, Persistent asthma, Phenotype, Polymorphism, Positional, Receptor, Respir, Respir crit care, Single nucleotide polymorphisms, Smoking status, Snp, Susceptibility, Thorax.
Abstract
Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.
Url:
DOI: 10.1136/thx.2009.119628
Links to Exploration step
ISTEX:6BD25A6F813E08C92DB2B5442D2D9CA69D30388CLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)</title><author><name sortKey="Castro Giner, F" sort="Castro Giner, F" uniqKey="Castro Giner F" first="F" last="Castro-Giner">F. Castro-Giner</name><affiliation><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="De Cid, R" sort="De Cid, R" uniqKey="De Cid R" first="R" last="De Cid">R. De Cid</name><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Gonzalez, J R" sort="Gonzalez, J R" uniqKey="Gonzalez J" first="J R" last="Gonzalez">J R Gonzalez</name><affiliation><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Jarvis, D" sort="Jarvis, D" uniqKey="Jarvis D" first="D" last="Jarvis">D. Jarvis</name><affiliation><mods:affiliation>Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK</mods:affiliation></affiliation></author><author><name sortKey="Heinrich, J" sort="Heinrich, J" uniqKey="Heinrich J" first="J" last="Heinrich">J. Heinrich</name><affiliation><mods:affiliation>Institute of Epidemiology, Helmholtz Zentrum München, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Janson, C" sort="Janson, C" uniqKey="Janson C" first="C" last="Janson">C. Janson</name><affiliation><mods:affiliation>Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Omenaas, E R" sort="Omenaas, E R" uniqKey="Omenaas E" first="E R" last="Omenaas">E R Omenaas</name><affiliation><mods:affiliation>Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</mods:affiliation></affiliation></author><author><name sortKey="Matheson, M C" sort="Matheson, M C" uniqKey="Matheson M" first="M C" last="Matheson">M C Matheson</name><affiliation><mods:affiliation>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia</mods:affiliation></affiliation></author><author><name sortKey="Pin, I" sort="Pin, I" uniqKey="Pin I" first="I" last="Pin">I. Pin</name><affiliation><mods:affiliation>Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche, France</mods:affiliation></affiliation><affiliation><mods:affiliation>University Joseph Fourier, Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre Hospitalier Universitaire de Grenoble, Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Ant, J M" sort="Ant, J M" uniqKey="Ant J" first="J M" last="Ant">J M Ant</name><affiliation><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Wjst, M" sort="Wjst, M" uniqKey="Wjst M" first="M" last="Wjst">M. Wjst</name><affiliation><mods:affiliation>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Estivill, X" sort="Estivill, X" uniqKey="Estivill X" first="X" last="Estivill">X. Estivill</name><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Kogevinas, M" sort="Kogevinas, M" uniqKey="Kogevinas M" first="M" last="Kogevinas">M. Kogevinas</name><affiliation><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>National School of Public Health, Athens, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: kogevinas@creal.cat</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:6BD25A6F813E08C92DB2B5442D2D9CA69D30388C</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1136/thx.2009.119628</idno><idno type="url">https://api.istex.fr/document/6BD25A6F813E08C92DB2B5442D2D9CA69D30388C/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001417</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001417</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)</title><author><name sortKey="Castro Giner, F" sort="Castro Giner, F" uniqKey="Castro Giner F" first="F" last="Castro-Giner">F. Castro-Giner</name><affiliation><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="De Cid, R" sort="De Cid, R" uniqKey="De Cid R" first="R" last="De Cid">R. De Cid</name><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Gonzalez, J R" sort="Gonzalez, J R" uniqKey="Gonzalez J" first="J R" last="Gonzalez">J R Gonzalez</name><affiliation><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Jarvis, D" sort="Jarvis, D" uniqKey="Jarvis D" first="D" last="Jarvis">D. Jarvis</name><affiliation><mods:affiliation>Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK</mods:affiliation></affiliation></author><author><name sortKey="Heinrich, J" sort="Heinrich, J" uniqKey="Heinrich J" first="J" last="Heinrich">J. Heinrich</name><affiliation><mods:affiliation>Institute of Epidemiology, Helmholtz Zentrum München, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Janson, C" sort="Janson, C" uniqKey="Janson C" first="C" last="Janson">C. Janson</name><affiliation><mods:affiliation>Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden</mods:affiliation></affiliation></author><author><name sortKey="Omenaas, E R" sort="Omenaas, E R" uniqKey="Omenaas E" first="E R" last="Omenaas">E R Omenaas</name><affiliation><mods:affiliation>Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</mods:affiliation></affiliation></author><author><name sortKey="Matheson, M C" sort="Matheson, M C" uniqKey="Matheson M" first="M C" last="Matheson">M C Matheson</name><affiliation><mods:affiliation>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia</mods:affiliation></affiliation></author><author><name sortKey="Pin, I" sort="Pin, I" uniqKey="Pin I" first="I" last="Pin">I. Pin</name><affiliation><mods:affiliation>Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche, France</mods:affiliation></affiliation><affiliation><mods:affiliation>University Joseph Fourier, Grenoble, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre Hospitalier Universitaire de Grenoble, Grenoble, France</mods:affiliation></affiliation></author><author><name sortKey="Ant, J M" sort="Ant, J M" uniqKey="Ant J" first="J M" last="Ant">J M Ant</name><affiliation><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Wjst, M" sort="Wjst, M" uniqKey="Wjst M" first="M" last="Wjst">M. Wjst</name><affiliation><mods:affiliation>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Estivill, X" sort="Estivill, X" uniqKey="Estivill X" first="X" last="Estivill">X. Estivill</name><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Kogevinas, M" sort="Kogevinas, M" uniqKey="Kogevinas M" first="M" last="Kogevinas">M. Kogevinas</name><affiliation><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>National School of Public Health, Athens, Greece</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: kogevinas@creal.cat</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Thorax</title><title level="j" type="abbrev">Thorax</title><idno type="ISSN">0040-6376</idno><idno type="eISSN">1468-3296</idno><imprint><publisher>BMJ Publishing Group Ltd and British Thoracic Society</publisher><date type="published" when="2010-02">2010-02</date><biblScope unit="volume">65</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="124">124</biblScope></imprint><idno type="ISSN">0040-6376</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0040-6376</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allergy</term><term>Asthma</term><term>Asthma susceptibility gene</term><term>Atopic</term><term>Atopic asthma</term><term>Atopy</term><term>Barcelona</term><term>Body mass index</term><term>Bonferroni</term><term>Bonferroni correction</term><term>Candidate genes</term><term>Chromosome</term><term>Clin</term><term>Cohort</term><term>Comparison group</term><term>Ecrhs</term><term>European community</term><term>Gene</term><term>Genet</term><term>Gure</term><term>Haplotype</term><term>Health survey</term><term>High serum</term><term>Locus</term><term>Npsr1</term><term>Npsr1 gene</term><term>Npsr1 polymorphisms</term><term>Npsr1 snps</term><term>Odds ratios</term><term>Online</term><term>Online supplement</term><term>Onset asthma</term><term>Other studies</term><term>Persistent asthma</term><term>Phenotype</term><term>Polymorphism</term><term>Positional</term><term>Receptor</term><term>Respir</term><term>Respir crit care</term><term>Single nucleotide polymorphisms</term><term>Smoking status</term><term>Snp</term><term>Susceptibility</term><term>Thorax</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Allergy</term><term>Asthma</term><term>Asthma susceptibility gene</term><term>Atopic</term><term>Atopic asthma</term><term>Atopy</term><term>Barcelona</term><term>Body mass index</term><term>Bonferroni</term><term>Bonferroni correction</term><term>Candidate genes</term><term>Chromosome</term><term>Clin</term><term>Cohort</term><term>Comparison group</term><term>Ecrhs</term><term>European community</term><term>Gene</term><term>Genet</term><term>Gure</term><term>Haplotype</term><term>Health survey</term><term>High serum</term><term>Locus</term><term>Npsr1</term><term>Npsr1 gene</term><term>Npsr1 polymorphisms</term><term>Npsr1 snps</term><term>Odds ratios</term><term>Online</term><term>Online supplement</term><term>Onset asthma</term><term>Other studies</term><term>Persistent asthma</term><term>Phenotype</term><term>Polymorphism</term><term>Positional</term><term>Receptor</term><term>Respir</term><term>Respir crit care</term><term>Single nucleotide polymorphisms</term><term>Smoking status</term><term>Snp</term><term>Susceptibility</term><term>Thorax</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.</div></front></TEI><istex><corpusName>bmj</corpusName><keywords><teeft><json:string>asthma</json:string><json:string>atopy</json:string><json:string>npsr1</json:string><json:string>polymorphism</json:string><json:string>atopic</json:string><json:string>ecrhs</json:string><json:string>receptor</json:string><json:string>atopic asthma</json:string><json:string>online</json:string><json:string>allergy</json:string><json:string>positional</json:string><json:string>haplotype</json:string><json:string>online supplement</json:string><json:string>phenotype</json:string><json:string>chromosome</json:string><json:string>clin</json:string><json:string>genet</json:string><json:string>gure</json:string><json:string>cohort</json:string><json:string>bonferroni</json:string><json:string>thorax</json:string><json:string>snp</json:string><json:string>respir</json:string><json:string>bonferroni correction</json:string><json:string>barcelona</json:string><json:string>european community</json:string><json:string>body mass index</json:string><json:string>smoking status</json:string><json:string>respir crit care</json:string><json:string>health survey</json:string><json:string>npsr1 polymorphisms</json:string><json:string>npsr1 gene</json:string><json:string>comparison group</json:string><json:string>high serum</json:string><json:string>onset asthma</json:string><json:string>npsr1 snps</json:string><json:string>persistent asthma</json:string><json:string>odds ratios</json:string><json:string>candidate genes</json:string><json:string>single nucleotide polymorphisms</json:string><json:string>asthma susceptibility gene</json:string><json:string>other studies</json:string><json:string>susceptibility</json:string><json:string>gene</json:string><json:string>locus</json:string></teeft></keywords><author><json:item><name>F Castro-Giner</name><affiliations><json:string>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</json:string><json:string>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</json:string><json:string>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</json:string></affiliations></json:item><json:item><name>R de Cid</name><affiliations><json:string>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</json:string><json:string>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</json:string></affiliations></json:item><json:item><name>J R Gonzalez</name><affiliations><json:string>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</json:string><json:string>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</json:string><json:string>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</json:string></affiliations></json:item><json:item><name>D Jarvis</name><affiliations><json:string>Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK</json:string></affiliations></json:item><json:item><name>J Heinrich</name><affiliations><json:string>Institute of Epidemiology, Helmholtz Zentrum München, Munich, Germany</json:string></affiliations></json:item><json:item><name>C Janson</name><affiliations><json:string>Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden</json:string></affiliations></json:item><json:item><name>E R Omenaas</name><affiliations><json:string>Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway</json:string><json:string>Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</json:string></affiliations></json:item><json:item><name>M C Matheson</name><affiliations><json:string>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia</json:string></affiliations></json:item><json:item><name>I Pin</name><affiliations><json:string>Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche, France</json:string><json:string>University Joseph Fourier, Grenoble, France</json:string><json:string>Centre Hospitalier Universitaire de Grenoble, Grenoble, France</json:string></affiliations></json:item><json:item><name>J M Antó</name><affiliations><json:string>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</json:string><json:string>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</json:string><json:string>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</json:string><json:string>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</json:string></affiliations></json:item><json:item><name>M Wjst</name><affiliations><json:string>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany</json:string></affiliations></json:item><json:item><name>X Estivill</name><affiliations><json:string>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</json:string><json:string>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</json:string><json:string>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</json:string></affiliations></json:item><json:item><name>M Kogevinas</name><affiliations><json:string>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</json:string><json:string>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</json:string><json:string>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</json:string><json:string>National School of Public Health, Athens, Greece</json:string><json:string>E-mail: kogevinas@creal.cat</json:string></affiliations></json:item></author><articleId><json:string>thorax119628</json:string></articleId><arkIstex>ark:/67375/NVC-68ZVVKDW-T</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p>0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.</abstract><qualityIndicators><score>9.916</score><pdfWordCount>5097</pdfWordCount><pdfCharCount>33971</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>8</pdfPageCount><pdfPageSize>595.276 x 793.701 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>243</abstractWordCount><abstractCharCount>1620</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)</title><pmid><json:string>19996348</json:string></pmid><genre><json:string>research-article</json:string></genre><host><title>Thorax</title><language><json:string>unknown</json:string></language><issn><json:string>0040-6376</json:string></issn><eissn><json:string>1468-3296</json:string></eissn><publisherId><json:string>Thorax</json:string></publisherId><volume>65</volume><issue>2</issue><pages><first>124</first></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2474</json:string><json:string>2009-12-08</json:string><json:string>1213</json:string></date><geogName></geogName><orgName><json:string>Institute of Epidemiology, Helmholtz Zentrum Munchen</json:string><json:string>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany</json:string><json:string>Uppsala University</json:string><json:string>Environmental, Genetic and Analytic Epidemiology</json:string><json:string>European Community Respiratory Health Survey Steering Committee</json:string><json:string>Spain Genes and Disease</json:string><json:string>Department of Medical Sciences, Respiratory Medicine</json:string><json:string>Municipal Institute of Medical Research</json:string><json:string>Environmental Epidemiology</json:string><json:string>Clinical Research, Haukeland University Hospital, Bergen, Norway</json:string><json:string>Program, Center for Genomic Regulation</json:string><json:string>SD</json:string><json:string>National Heart and Lung</json:string><json:string>National School of Public Health, Athens, Greece</json:string><json:string>Department of Health and Experimental Sciences</json:string><json:string>University of Melbourne</json:string><json:string>Pharmacia Diagnostics, Uppsala, Sweden</json:string><json:string>Variable Country Australia France Germany Norway Spain Sweden Switzerland UK Sex Men Women Smoking Never Ex Current Mean</json:string><json:string>Sweden Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway</json:string><json:string>CREAL</json:string><json:string>Genome Spain</json:string><json:string>Catalonia</json:string><json:string>MaratoTV3</json:string><json:string>Spain</json:string></orgName><orgName_funder><json:string>Genome Spain</json:string><json:string>Catalonia</json:string><json:string>MaratoTV3</json:string><json:string>Spain</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Senior</json:string><json:string>Joseph Fourier</json:string><json:string>Investigators</json:string><json:string>Albert Bonniot</json:string><json:string>La Tronche</json:string><json:string>Universitaire</json:string></persName><placeName><json:string>Erfurt</json:string><json:string>Foster City</json:string><json:string>Uppsala</json:string><json:string>Switzerland</json:string><json:string>Germany</json:string><json:string>Munich</json:string><json:string>Australia</json:string><json:string>Grenoble</json:string><json:string>UK</json:string><json:string>Albacete</json:string><json:string>Norway</json:string><json:string>Huelva</json:string><json:string>Melbourne</json:string><json:string>Ipswich</json:string><json:string>London</json:string><json:string>Victoria</json:string><json:string>Jaen</json:string><json:string>Norwich</json:string><json:string>Barcelona</json:string><json:string>Bergen</json:string><json:string>Basel</json:string><json:string>France</json:string><json:string>Burgos</json:string><json:string>Sweden</json:string><json:string>Spain</json:string><json:string>Oviedo</json:string></placeName><ref_url><json:string>http://thorax.bmj</json:string></ref_url><ref_bibl><json:string>Bouzigon et al</json:string><json:string>R Foundation for Statistical Computing, Vienna, Austria, 2007</json:string><json:string>Hersh et al</json:string><json:string>Bouzigon et al.</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/NVC-68ZVVKDW-T</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - respiratory system</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - respiratory system</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Pulmonary and Respiratory Medicine</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>2010</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1136/thx.2009.119628</json:string></doi><id>6BD25A6F813E08C92DB2B5442D2D9CA69D30388C</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/6BD25A6F813E08C92DB2B5442D2D9CA69D30388C/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/6BD25A6F813E08C92DB2B5442D2D9CA69D30388C/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/6BD25A6F813E08C92DB2B5442D2D9CA69D30388C/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://publisher-list.data.istex.fr">BMJ Publishing Group Ltd and British Thoracic Society</publisher><availability><licence><p>© 2010, Published by the BMJ Publishing Group Limited For permission to use, (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-7M42M2QJ-2">bmj</p></availability><date>2009-12-08</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note>Additional data are published online only at http://thorax.bmj.com/content/vol65/issue2</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)</title><author xml:id="author-0000"><persName><forename type="first">F</forename><surname>Castro-Giner</surname></persName><affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</affiliation><affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</affiliation><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation></author><author xml:id="author-0001"><persName><forename type="first">R</forename><surname>de Cid</surname></persName><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</affiliation></author><author xml:id="author-0002"><persName><forename type="first">J R</forename><surname>Gonzalez</surname></persName><affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</affiliation><affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</affiliation><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation></author><author xml:id="author-0003"><persName><forename type="first">D</forename><surname>Jarvis</surname></persName><affiliation>Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK</affiliation></author><author xml:id="author-0004"><persName><forename type="first">J</forename><surname>Heinrich</surname></persName><affiliation>Institute of Epidemiology, Helmholtz Zentrum München, Munich, Germany</affiliation></author><author xml:id="author-0005"><persName><forename type="first">C</forename><surname>Janson</surname></persName><affiliation>Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden</affiliation></author><author xml:id="author-0006"><persName><forename type="first">E R</forename><surname>Omenaas</surname></persName><affiliation>Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway</affiliation><affiliation>Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</affiliation></author><author xml:id="author-0007"><persName><forename type="first">M C</forename><surname>Matheson</surname></persName><affiliation>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia</affiliation></author><author xml:id="author-0008"><persName><forename type="first">I</forename><surname>Pin</surname></persName><affiliation>Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche, France</affiliation><affiliation>University Joseph Fourier, Grenoble, France</affiliation><affiliation>Centre Hospitalier Universitaire de Grenoble, Grenoble, France</affiliation></author><author xml:id="author-0009"><persName><forename type="first">J M</forename><surname>Antó</surname></persName><affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</affiliation><affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</affiliation><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</affiliation></author><author xml:id="author-0010"><persName><forename type="first">M</forename><surname>Wjst</surname></persName><affiliation>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany</affiliation></author><author xml:id="author-0011"><persName><forename type="first">X</forename><surname>Estivill</surname></persName><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</affiliation><affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</affiliation></author><author xml:id="author-0012" corresp="yes"><persName><forename type="first">M</forename><surname>Kogevinas</surname></persName><email>kogevinas@creal.cat</email><affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</affiliation><affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</affiliation><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><affiliation>National School of Public Health, Athens, Greece</affiliation></author><idno type="istex">6BD25A6F813E08C92DB2B5442D2D9CA69D30388C</idno><idno type="ark">ark:/67375/NVC-68ZVVKDW-T</idno><idno type="DOI">10.1136/thx.2009.119628</idno><idno type="href">thoraxjnl-65-124.pdf</idno><idno type="article-id">thorax119628</idno><idno type="PMID">19996348</idno><idno type="local">thoraxjnl;65/2/124</idno></analytic><monogr><title level="j">Thorax</title><title level="j" type="abbrev">Thorax</title><idno type="pISSN">0040-6376</idno><idno type="eISSN">1468-3296</idno><idno type="publisher-id">Thorax</idno><idno type="PublisherID-hwp">thoraxjnl</idno><idno type="PublisherID-nlm-ta">Thorax</idno><imprint><publisher>BMJ Publishing Group Ltd and British Thoracic Society</publisher><date type="published" when="2010-02"></date><biblScope unit="volume">65</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="124">124</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009-12-08</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.</p></abstract></profileDesc><revisionDesc><change when="2009-12-08">Created</change><change when="2010-02">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/6BD25A6F813E08C92DB2B5442D2D9CA69D30388C/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" URI="archivearticle.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">thoraxjnl</journal-id><journal-id journal-id-type="nlm-ta">Thorax</journal-id><journal-id journal-id-type="publisher-id">Thorax</journal-id><journal-title>Thorax</journal-title><abbrev-journal-title abbrev-type="publisher">Thorax</abbrev-journal-title><abbrev-journal-title>Thorax</abbrev-journal-title><issn pub-type="ppub">0040-6376</issn><issn pub-type="epub">1468-3296</issn><publisher><publisher-name>BMJ Publishing Group Ltd and British Thoracic Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">thorax119628</article-id><article-id pub-id-type="doi">10.1136/thx.2009.119628</article-id><article-id pub-id-type="other">thoraxjnl;65/2/124</article-id><article-id pub-id-type="other">thoraxjnl;thx.2009.119628</article-id><article-id pub-id-type="pmid">19996348</article-id><article-id pub-id-type="other">124</article-id><article-id pub-id-type="other">thx.2009.119628</article-id><article-categories><subj-group subj-group-type="heading"><subject>Asthma</subject></subj-group></article-categories><title-group><article-title>Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Castro-Giner</surname><given-names>F</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>de Cid</surname><given-names>R</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Gonzalez</surname><given-names>J R</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Jarvis</surname><given-names>D</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Heinrich</surname><given-names>J</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Janson</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Omenaas</surname><given-names>E R</given-names></name><xref ref-type="aff" rid="aff8">8</xref><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Matheson</surname><given-names>M C</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author"><name><surname>Pin</surname><given-names>I</given-names></name><xref ref-type="aff" rid="aff11">11</xref><xref ref-type="aff" rid="aff12">12</xref><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Antó</surname><given-names>J M</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff14">14</xref></contrib><contrib contrib-type="author"><name><surname>Wjst</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff15">15</xref></contrib><contrib contrib-type="author"><name><surname>Estivill</surname><given-names>X</given-names></name><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff14">14</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Kogevinas</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff16">16</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</aff><aff id="aff2"><label>2</label>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</aff><aff id="aff3"><label>3</label>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</aff><aff id="aff4"><label>4</label>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</aff><aff id="aff5"><label>5</label>Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK</aff><aff id="aff6"><label>6</label>Institute of Epidemiology, Helmholtz Zentrum München, Munich, Germany</aff><aff id="aff7"><label>7</label>Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden</aff><aff id="aff8"><label>8</label>Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway</aff><aff id="aff9"><label>9</label>Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</aff><aff id="aff10"><label>10</label>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia</aff><aff id="aff11"><label>11</label>Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche, France</aff><aff id="aff12"><label>12</label>University Joseph Fourier, Grenoble, France</aff><aff id="aff13"><label>13</label>Centre Hospitalier Universitaire de Grenoble, Grenoble, France</aff><aff id="aff14"><label>14</label>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</aff><aff id="aff15"><label>15</label>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany</aff><aff id="aff16"><label>16</label>National School of Public Health, Athens, Greece</aff><author-notes><corresp><label>Correspondence to</label> Dr M Kogevinas, Centre for Research in Environmental Epidemiology, 88 Dr Aiguader Rd, Barcelona 08003, Spain; <email>kogevinas@creal.cat</email></corresp><fn fn-type="other"><p>Additional data are published online only at <ext-link ext-link-type="uri" xlink:href="http://thorax.bmj.com/content/vol65/issue2">http://thorax.bmj.com/content/vol65/issue2</ext-link></p></fn></author-notes><pub-date pub-type="epub-original"><day>8</day><month>12</month><year>2009</year></pub-date><pub-date pub-type="ppub"><month>2</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>8</day><month>12</month><year>2009</year></pub-date><volume>65</volume><volume-id pub-id-type="other">65</volume-id><volume-id pub-id-type="other">65</volume-id><issue>2</issue><issue-id pub-id-type="other">thoraxjnl;65/2</issue-id><issue-id pub-id-type="other">2</issue-id><issue-id pub-id-type="other">65/2</issue-id><fpage>124</fpage><history><date date-type="received"><day>15</day><month>5</month><year>2009</year></date><date date-type="accepted"><day>29</day><month>10</month><year>2009</year></date></history><permissions><copyright-statement>© 2010, Published by the BMJ Publishing Group Limited For permission to use, (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</copyright-statement><copyright-year>2010</copyright-year></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="thoraxjnl-65-124.pdf"></self-uri><abstract><sec><title>Background</title><p>Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (<italic>ADAM33, PHF11, NPSR1, DPP10, SPINK5</italic>).</p></sec><sec><title>Methods</title><p>51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens.</p></sec><sec><title>Results</title><p>Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the <italic>NPSR1</italic> gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with <italic>NPSR1</italic> were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for <italic>ADAM33</italic> and BHR and for an age-specific effect of two SNPs in <italic>DPP10</italic> and asthma was weaker.</p></sec><sec><title>Conclusion</title><p>This study provides further evidence for an effect of <italic>NPSR1</italic> on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for <italic>NPSR1</italic> in early-onset asthma driven by the strong effect of this gene on atopic asthma.</p></sec></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)</title></titleInfo><name type="personal"><namePart type="given">F</namePart><namePart type="family">Castro-Giner</namePart><affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</affiliation><affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</affiliation><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">de Cid</namePart><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J R</namePart><namePart type="family">Gonzalez</namePart><affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</affiliation><affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</affiliation><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Jarvis</namePart><affiliation>Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Heinrich</namePart><affiliation>Institute of Epidemiology, Helmholtz Zentrum München, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Janson</namePart><affiliation>Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E R</namePart><namePart type="family">Omenaas</namePart><affiliation>Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway</affiliation><affiliation>Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M C</namePart><namePart type="family">Matheson</namePart><affiliation>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">I</namePart><namePart type="family">Pin</namePart><affiliation>Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche, France</affiliation><affiliation>University Joseph Fourier, Grenoble, France</affiliation><affiliation>Centre Hospitalier Universitaire de Grenoble, Grenoble, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J M</namePart><namePart type="family">Antó</namePart><affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</affiliation><affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</affiliation><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Wjst</namePart><affiliation>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">X</namePart><namePart type="family">Estivill</namePart><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</affiliation><affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">M</namePart><namePart type="family">Kogevinas</namePart><affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</affiliation><affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</affiliation><affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</affiliation><affiliation>National School of Public Health, Athens, Greece</affiliation><affiliation>E-mail: kogevinas@creal.cat</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>BMJ Publishing Group Ltd and British Thoracic Society</publisher><dateIssued encoding="w3cdtf">2010-02</dateIssued><dateCreated encoding="w3cdtf">2009-12-08</dateCreated><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract>Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.</abstract><note type="footnotes">Additional data are published online only at http://thorax.bmj.com/content/vol65/issue2</note><relatedItem type="host"><titleInfo><title>Thorax</title></titleInfo><titleInfo type="abbreviated"><title>Thorax</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">0040-6376</identifier><identifier type="eISSN">1468-3296</identifier><identifier type="PublisherID">Thorax</identifier><identifier type="PublisherID-hwp">thoraxjnl</identifier><identifier type="PublisherID-nlm-ta">Thorax</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>65</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>124</start></extent></part></relatedItem><identifier type="istex">6BD25A6F813E08C92DB2B5442D2D9CA69D30388C</identifier><identifier type="ark">ark:/67375/NVC-68ZVVKDW-T</identifier><identifier type="DOI">10.1136/thx.2009.119628</identifier><identifier type="href">thoraxjnl-65-124.pdf</identifier><identifier type="ArticleID">thorax119628</identifier><identifier type="PMID">19996348</identifier><identifier type="local">thoraxjnl;65/2/124</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2010, Published by the BMJ Publishing Group Limited For permission to use, (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-7M42M2QJ-2">bmj</recordContentSource><recordOrigin>© 2010, Published by the BMJ Publishing Group Limited For permission to use, (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/6BD25A6F813E08C92DB2B5442D2D9CA69D30388C/metadata/json</uri></json:item></metadata><annexes><json:item><extension>jpeg</extension><original>true</original><mimetype>image/jpeg</mimetype><uri>https://api.istex.fr/document/6BD25A6F813E08C92DB2B5442D2D9CA69D30388C/annexes/jpeg</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001417 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 001417 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Istex
|étape= Corpus
|type= RBID
|clé= ISTEX:6BD25A6F813E08C92DB2B5442D2D9CA69D30388C
|texte= Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)
}}
| This area was generated with Dilib version V0.6.33. |  |