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Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy

Identifieur interne : 000705 ( Ncbi/Curation ); précédent : 000704; suivant : 000706

Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy

Auteurs : Emmanuelle Bouzigon [France] ; Paola Forabosco [Royaume-Uni, Italie] ; Gerard H. Koppelman [Pays-Bas] ; William O C M. Cookson [Royaume-Uni] ; Marie-Hélène Dizier [France] ; David L. Duffy [Australie] ; David M. Evans [Royaume-Uni] ; Manuel A R. Ferreira [Australie] ; Juha Kere [Suède] ; Tarja Laitinen [Finlande] ; Giovanni Malerba [Italie] ; Deborah A. Meyers [États-Unis] ; Miriam Moffatt [Royaume-Uni] ; Nicholas G. Martin [Australie] ; Mandy Y. Ng [Royaume-Uni] ; Pier Franco Pignatti [Italie] ; Mathias Wjst [Allemagne, Italie] ; Francine Kauffmann [France] ; Florence Demenais [France] ; Cathryn M. Lewis [Royaume-Uni]

Source :

RBID : PMC:2987334

Abstract

Asthma is caused by a heterogeneous combination of environmental and genetic factors. In the context of GA2LEN (Global Allergy and Asthma European Network), we carried out meta-analyses of almost all genome-wide linkage screens conducted to date in 20 independent populations from different ethnic origins (≥3024 families with ≥10 027 subjects) for asthma, atopic asthma, bronchial hyper-responsiveness and five atopy-related traits (total immunoglobulin E level, positive skin test response (SPT) to at least one allergen or to House Dust Mite, quantitative score of SPT (SPTQ) and eosinophils (EOS)). We used the genome scan meta-analysis method to assess evidence for linkage within bins of traditionally 30-cM width, and explored the manner in which these results were affected by bin definition. Meta-analyses were conducted in all studies and repeated in families of European ancestry. Genome-wide evidence for linkage was detected for asthma in two regions (2p21–p14 and 6p21) in European families ascertained through two asthmatic sibs. With regard to atopy phenotypes, four regions reached genome-wide significance: 3p25.3–q24 in all families for SPT and three other regions in European families (2q32–q34 for EOS, 5q23–q33 for SPTQ and 17q12–q24 for SPT). Tests of heterogeneity showed consistent evidence of linkage of SPTQ to 3p11–3q21, whereas between-study heterogeneity was detected for asthma in 2p22–p13 and 6p21, and for atopic asthma in 1q23–q25. This large-scale meta-analysis provides an important resource of information that can be used to prioritize further fine-mapping studies and also be integrated with genome-wide association studies to increase power and better interpret the outcomes of these studies.


Url:
DOI: 10.1038/ejhg.2009.224
PubMed: 20068594
PubMed Central: 2987334

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PMC:2987334

Le document en format XML

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<institution>Université Paris Diderot, Paris 7, Institut Universitaire d'Hématologie</institution>
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<institution>Istituto di Genetica delle Popolazioni-CNR</institution>
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<institution>Queensland Institute of Medical Research, Royal Brisbane Hospital</institution>
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<name sortKey="Kere, Juha" sort="Kere, Juha" uniqKey="Kere J" first="Juha" last="Kere">Juha Kere</name>
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, Stockholm,
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<name sortKey="Laitinen, Tarja" sort="Laitinen, Tarja" uniqKey="Laitinen T" first="Tarja" last="Laitinen">Tarja Laitinen</name>
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<institution>Departments of Pulmonary Medicine and Medical Genetics, University of Helsinki</institution>
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<country xml:lang="fr">Finlande</country>
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<name sortKey="Malerba, Giovanni" sort="Malerba, Giovanni" uniqKey="Malerba G" first="Giovanni" last="Malerba">Giovanni Malerba</name>
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<name sortKey="Moffatt, Miriam" sort="Moffatt, Miriam" uniqKey="Moffatt M" first="Miriam" last="Moffatt">Miriam Moffatt</name>
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<name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name>
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<name sortKey="Ng, Mandy Y" sort="Ng, Mandy Y" uniqKey="Ng M" first="Mandy Y" last="Ng">Mandy Y. Ng</name>
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<name sortKey="Pignatti, Pier Franco" sort="Pignatti, Pier Franco" uniqKey="Pignatti P" first="Pier Franco" last="Pignatti">Pier Franco Pignatti</name>
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<institution>Section of Biology and Genetics, Department of Mother and Child, and Biology-Genetics, University of Verona</institution>
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</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Wjst, Mathias" sort="Wjst, Mathias" uniqKey="Wjst M" first="Mathias" last="Wjst">Mathias Wjst</name>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Kauffmann, Francine" sort="Kauffmann, Francine" uniqKey="Kauffmann F" first="Francine" last="Kauffmann">Francine Kauffmann</name>
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<institution>Univ Paris-Sud, IFR69</institution>
, Villejuif,
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<country xml:lang="fr">France</country>
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<name sortKey="Demenais, Florence" sort="Demenais, Florence" uniqKey="Demenais F" first="Florence" last="Demenais">Florence Demenais</name>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>Foundation Jean Dausset-Centre d'Etude du Polymorphisme Humain (CEPH)</institution>
, Paris,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
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<name sortKey="Lewis, Cathryn M" sort="Lewis, Cathryn M" uniqKey="Lewis C" first="Cathryn M" last="Lewis">Cathryn M. Lewis</name>
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<institution>King's College London, Department of Medical and Molecular Genetics</institution>
, London,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
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<institution>King's College London, MRC SGDP Centre, Institute of Psychiatry</institution>
, London,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<title xml:lang="en" level="a" type="main">Meta-analysis of 20 genome-wide linkage studies evidenced new regions linked to asthma and atopy</title>
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, Paris,
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Forabosco, Paola" sort="Forabosco, Paola" uniqKey="Forabosco P" first="Paola" last="Forabosco">Paola Forabosco</name>
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</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Koppelman, Gerard H" sort="Koppelman, Gerard H" uniqKey="Koppelman G" first="Gerard H" last="Koppelman">Gerard H. Koppelman</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Cookson, William O C M" sort="Cookson, William O C M" uniqKey="Cookson W" first="William O C M" last="Cookson">William O C M. Cookson</name>
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<name sortKey="Dizier, Marie Helene" sort="Dizier, Marie Helene" uniqKey="Dizier M" first="Marie-Hélène" last="Dizier">Marie-Hélène Dizier</name>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<nlm:aff id="aff9">
<institution>Univ Paris-Sud, IFR69</institution>
, Villejuif,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<name sortKey="Duffy, David L" sort="Duffy, David L" uniqKey="Duffy D" first="David L" last="Duffy">David L. Duffy</name>
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<institution>Queensland Institute of Medical Research, Royal Brisbane Hospital</institution>
, Brisbane,
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<name sortKey="Evans, David M" sort="Evans, David M" uniqKey="Evans D" first="David M" last="Evans">David M. Evans</name>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Department of Social Medicine, University of Bristol</institution>
, Bristol,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<name sortKey="Ferreira, Manuel A R" sort="Ferreira, Manuel A R" uniqKey="Ferreira M" first="Manuel A R" last="Ferreira">Manuel A R. Ferreira</name>
<affiliation wicri:level="1">
<nlm:aff id="aff10">
<institution>Queensland Institute of Medical Research, Royal Brisbane Hospital</institution>
, Brisbane,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author>
<name sortKey="Kere, Juha" sort="Kere, Juha" uniqKey="Kere J" first="Juha" last="Kere">Juha Kere</name>
<affiliation wicri:level="1">
<nlm:aff id="aff12">
<institution>Department of Biosciences and Nutrition, Karolinska Institute</institution>
, Stockholm,
<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Laitinen, Tarja" sort="Laitinen, Tarja" uniqKey="Laitinen T" first="Tarja" last="Laitinen">Tarja Laitinen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff13">
<institution>Departments of Pulmonary Medicine and Medical Genetics, University of Helsinki</institution>
, Helsinki,
<country>Finland</country>
</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Malerba, Giovanni" sort="Malerba, Giovanni" uniqKey="Malerba G" first="Giovanni" last="Malerba">Giovanni Malerba</name>
<affiliation wicri:level="1">
<nlm:aff id="aff14">
<institution>Section of Biology and Genetics, Department of Mother and Child, and Biology-Genetics, University of Verona</institution>
, Verona,
<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Meyers, Deborah A" sort="Meyers, Deborah A" uniqKey="Meyers D" first="Deborah A" last="Meyers">Deborah A. Meyers</name>
<affiliation wicri:level="1">
<nlm:aff id="aff15">
<institution>Center for Human Genomics, Wake Forest University</institution>
, Winston Salem, NC,
<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Moffatt, Miriam" sort="Moffatt, Miriam" uniqKey="Moffatt M" first="Miriam" last="Moffatt">Miriam Moffatt</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>National Heart Lung Institute, Imperial College</institution>
, London,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff10">
<institution>Queensland Institute of Medical Research, Royal Brisbane Hospital</institution>
, Brisbane,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ng, Mandy Y" sort="Ng, Mandy Y" uniqKey="Ng M" first="Mandy Y" last="Ng">Mandy Y. Ng</name>
<affiliation wicri:level="1">
<nlm:aff id="aff16">
<institution>King's College London, MRC SGDP Centre, Institute of Psychiatry</institution>
, London,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Pignatti, Pier Franco" sort="Pignatti, Pier Franco" uniqKey="Pignatti P" first="Pier Franco" last="Pignatti">Pier Franco Pignatti</name>
<affiliation wicri:level="1">
<nlm:aff id="aff14">
<institution>Section of Biology and Genetics, Department of Mother and Child, and Biology-Genetics, University of Verona</institution>
, Verona,
<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wjst, Mathias" sort="Wjst, Mathias" uniqKey="Wjst M" first="Mathias" last="Wjst">Mathias Wjst</name>
<affiliation wicri:level="1">
<nlm:aff id="aff17">
<institution>Institute of Experimental Pneumology, Helmholtz Zentrum München, German Research Center for Environmental Health</institution>
, Neuherberg,
<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff18">
<institution>Institute of Genetic Medicine, EURAC research</institution>
, Bozen,
<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kauffmann, Francine" sort="Kauffmann, Francine" uniqKey="Kauffmann F" first="Francine" last="Kauffmann">Francine Kauffmann</name>
<affiliation wicri:level="1">
<nlm:aff id="aff9">
<institution>Univ Paris-Sud, IFR69</institution>
, Villejuif,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff19">
<institution>INSERM, U780</institution>
, Villejuif,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Demenais, Florence" sort="Demenais, Florence" uniqKey="Demenais F" first="Florence" last="Demenais">Florence Demenais</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>INSERM, U946</institution>
, Paris,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Université Paris Diderot, Paris 7, Institut Universitaire d'Hématologie</institution>
, Paris,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>Foundation Jean Dausset-Centre d'Etude du Polymorphisme Humain (CEPH)</institution>
, Paris,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lewis, Cathryn M" sort="Lewis, Cathryn M" uniqKey="Lewis C" first="Cathryn M" last="Lewis">Cathryn M. Lewis</name>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>King's College London, Department of Medical and Molecular Genetics</institution>
, London,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff16">
<institution>King's College London, MRC SGDP Centre, Institute of Psychiatry</institution>
, London,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">European Journal of Human Genetics</title>
<idno type="ISSN">1018-4813</idno>
<idno type="eISSN">1476-5438</idno>
<imprint>
<date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Asthma is caused by a heterogeneous combination of environmental and genetic factors. In the context of GA2LEN (Global Allergy and Asthma European Network), we carried out meta-analyses of almost all genome-wide linkage screens conducted to date in 20 independent populations from different ethnic origins (≥3024 families with ≥10 027 subjects) for asthma, atopic asthma, bronchial hyper-responsiveness and five atopy-related traits (total immunoglobulin E level, positive skin test response (SPT) to at least one allergen or to House Dust Mite, quantitative score of SPT (SPTQ) and eosinophils (EOS)). We used the genome scan meta-analysis method to assess evidence for linkage within bins of traditionally 30-cM width, and explored the manner in which these results were affected by bin definition. Meta-analyses were conducted in all studies and repeated in families of European ancestry. Genome-wide evidence for linkage was detected for asthma in two regions (2p21–p14 and 6p21) in European families ascertained through two asthmatic sibs. With regard to atopy phenotypes, four regions reached genome-wide significance: 3p25.3–q24 in all families for SPT and three other regions in European families (2q32–q34 for EOS, 5q23–q33 for SPTQ and 17q12–q24 for SPT). Tests of heterogeneity showed consistent evidence of linkage of SPTQ to 3p11–3q21, whereas between-study heterogeneity was detected for asthma in 2p22–p13 and 6p21, and for atopic asthma in 1q23–q25. This large-scale meta-analysis provides an important resource of information that can be used to prioritize further fine-mapping studies and also be integrated with genome-wide association studies to increase power and better interpret the outcomes of these studies.</p>
</div>
</front>
</TEI>
</record>

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