Association of Forced Vital Capacity with the Developmental Gene NCOR2
Identifieur interne : 002332 ( Main/Exploration ); précédent : 002331; suivant : 002333Association of Forced Vital Capacity with the Developmental Gene NCOR2
Auteurs : Cosetta Minelli [Royaume-Uni] ; Charlotte H. Dean [Royaume-Uni] ; Matthew Hind [Royaume-Uni] ; Alexessander Couto Alves [Royaume-Uni] ; André F. S. Amaral [Royaume-Uni] ; Valerie Siroux [France] ; Ville Huikari [Finlande] ; María Soler Artigas [Royaume-Uni] ; David M. Evans [Australie, Royaume-Uni] ; Daan W. Loth [Pays-Bas] ; Yohan Bossé [Canada] ; Dirkje S. Postma [Pays-Bas] ; Don Sin [Canada] ; John Thompson [Royaume-Uni] ; Florence Demenais [France] ; John Henderson [Royaume-Uni] ; Emmanuelle Bouzigon [France] ; Deborah Jarvis [Royaume-Uni] ; Marjo-Riitta J Rvelin [Royaume-Uni, Finlande] ; Peter Burney [Royaume-Uni]Source :
- PLoS ONE [ 1932-6203 ] ; 2016.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Analyse de profil d'expression de gènes, Corépresseur-2 de récepteur nucléaire (génétique), Corépresseur-2 de récepteur nucléaire (métabolisme), Femelle, Gènes du développement, Humains, Jeune adulte, Locus de caractère quantitatif, Mâle, Organogenèse (génétique), Polymorphisme de nucléotide simple, Poumon (embryologie), Poumon (métabolisme), Sujet âgé, Volume expiratoire maximal par seconde (génétique), Étude d'association pangénomique, Études d'associations génétiques.
- MESH :
- embryologie : Poumon.
- génétique : Corépresseur-2 de récepteur nucléaire, Organogenèse, Volume expiratoire maximal par seconde.
- métabolisme : Corépresseur-2 de récepteur nucléaire, Poumon.
- Adulte, Adulte d'âge moyen, Analyse de profil d'expression de gènes, Femelle, Gènes du développement, Humains, Jeune adulte, Locus de caractère quantitatif, Mâle, Polymorphisme de nucléotide simple, Sujet âgé, Étude d'association pangénomique, Études d'associations génétiques.
English descriptors
- KwdEn :
- Adult, Aged, Female, Forced Expiratory Volume (genetics), Gene Expression Profiling, Genes, Developmental, Genetic Association Studies, Genome-Wide Association Study, Humans, Lung (embryology), Lung (metabolism), Male, Middle Aged, Nuclear Receptor Co-Repressor 2 (genetics), Nuclear Receptor Co-Repressor 2 (metabolism), Organogenesis (genetics), Polymorphism, Single Nucleotide, Quantitative Trait Loci, Young Adult.
- MESH :
- chemical , genetics : Nuclear Receptor Co-Repressor 2.
- embryology : Lung.
- genetics : Forced Expiratory Volume, Organogenesis.
- metabolism : Lung, Nuclear Receptor Co-Repressor 2.
- Adult, Aged, Female, Gene Expression Profiling, Genes, Developmental, Genetic Association Studies, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Young Adult.
Abstract
Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes.
Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (
We have identified a new gene,
Url:
DOI: 10.1371/journal.pone.0147388
PubMed: 26836265
PubMed Central: 4737618
Affiliations:
- Australie, Canada, Finlande, France, Pays-Bas, Royaume-Uni
- Angleterre, Auvergne-Rhône-Alpes, Grand Londres, Groningue (province), Hollande-Méridionale, Rhône-Alpes, Île-de-France
- Grenoble, Groningue, Groningue (ville), Londres, Paris, Rotterdam
- Université de Groningue
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Le document en format XML
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Evans</name><affiliation wicri:level="1"><nlm:aff id="aff012"><addr-line>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff013"><addr-line>MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Loth, Daan W" sort="Loth, Daan W" uniqKey="Loth D" first="Daan W." last="Loth">Daan W. Loth</name><affiliation wicri:level="3"><nlm:aff id="aff014"><addr-line>Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Bosse, Yohan" sort="Bosse, Yohan" uniqKey="Bosse Y" first="Yohan" last="Bossé">Yohan Bossé</name><affiliation wicri:level="1"><nlm:aff id="aff015"><addr-line>Institut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Institut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Postma, Dirkje S" sort="Postma, Dirkje S" uniqKey="Postma D" first="Dirkje S." last="Postma">Dirkje S. Postma</name><affiliation wicri:level="4"><nlm:aff id="aff016"><addr-line>Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Sin, Don" sort="Sin, Don" uniqKey="Sin D" first="Don" last="Sin">Don Sin</name><affiliation wicri:level="1"><nlm:aff id="aff017"><addr-line>The University of British Columbia Center for Heart Lung Innovation, St-Paul’s Hospital, Vancouver, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The University of British Columbia Center for Heart Lung Innovation, St-Paul’s Hospital, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author><author><name sortKey="Thompson, John" sort="Thompson, John" uniqKey="Thompson J" first="John" last="Thompson">John Thompson</name><affiliation wicri:level="1"><nlm:aff id="aff018"><addr-line>Department of Health Sciences, University of Leicester, Leicester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Health Sciences, University of Leicester, Leicester</wicri:regionArea><wicri:noRegion>Leicester</wicri:noRegion></affiliation></author><author><name sortKey="Demenais, Florence" sort="Demenais, Florence" uniqKey="Demenais F" first="Florence" last="Demenais">Florence Demenais</name><affiliation wicri:level="3"><nlm:aff id="aff019"><addr-line>INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff020"><addr-line>Univ. Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, F-75007, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ. Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, F-75007, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Henderson, John" sort="Henderson, John" uniqKey="Henderson J" first="John" last="Henderson">John Henderson</name><affiliation wicri:level="1"><nlm:aff id="aff021"><addr-line>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Bouzigon, Emmanuelle" sort="Bouzigon, Emmanuelle" uniqKey="Bouzigon E" first="Emmanuelle" last="Bouzigon">Emmanuelle Bouzigon</name><affiliation wicri:level="3"><nlm:aff id="aff019"><addr-line>INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff020"><addr-line>Univ. Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, F-75007, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ. Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, F-75007, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Jarvis, Deborah" sort="Jarvis, Deborah" uniqKey="Jarvis D" first="Deborah" last="Jarvis">Deborah Jarvis</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>MRC-PHE Centre for Environment & Health, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC-PHE Centre for Environment & Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>MRC-PHE Centre for Environment & Health, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC-PHE Centre for Environment & Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Biocenter Oulu, University of Oulu, Oulu, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Biocenter Oulu, University of Oulu, Oulu</wicri:regionArea><wicri:noRegion>Oulu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff024"><addr-line>Center for Life Course Epidemiology, Faculty of Medicine, P.O. Box 5000, FI-90014 University of Oulu, Oulu, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Center for Life Course Epidemiology, Faculty of Medicine, P.O. Box 5000, FI-90014 University of Oulu, Oulu</wicri:regionArea><wicri:noRegion>Oulu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff025"><addr-line>Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. Box 20, FI-90220, Oulu, 90029 OYS, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. 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Dean</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Leukocyte Biology, National Heart and Lung Institute, Imperial College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Leukocyte Biology, National Heart and Lung Institute, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Mammalian Genetics Unit, MRC Harwell, Oxon, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Mammalian Genetics Unit, MRC Harwell, Oxon</wicri:regionArea><wicri:noRegion>Oxon</wicri:noRegion></affiliation></author><author><name sortKey="Hind, Matthew" sort="Hind, Matthew" uniqKey="Hind M" first="Matthew" last="Hind">Matthew Hind</name><affiliation wicri:level="3"><nlm:aff id="aff004"><addr-line>Respiratory Department, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Respiratory Department, Royal Brompton and Harefield NHS Foundation Trust, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Alves, Alexessander Couto" sort="Alves, Alexessander Couto" uniqKey="Alves A" first="Alexessander Couto" last="Alves">Alexessander Couto Alves</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Amaral, Andre F S" sort="Amaral, Andre F S" uniqKey="Amaral A" first="André F. S." last="Amaral">André F. S. Amaral</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>MRC-PHE Centre for Environment & Health, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC-PHE Centre for Environment & Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Siroux, Valerie" sort="Siroux, Valerie" uniqKey="Siroux V" first="Valerie" last="Siroux">Valerie Siroux</name><affiliation wicri:level="3"><nlm:aff id="aff007"><addr-line>Univ. Grenoble Alpes, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, F-38000, Grenoble, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ. Grenoble Alpes, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, F-38000, Grenoble</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff008"><addr-line>INSERM, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, F-38000, Grenoble, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, F-38000, Grenoble</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff009"><addr-line>CHU de Grenoble, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, F-38000, Grenoble, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CHU de Grenoble, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, F-38000, Grenoble</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Huikari, Ville" sort="Huikari, Ville" uniqKey="Huikari V" first="Ville" last="Huikari">Ville Huikari</name><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Biocenter Oulu, University of Oulu, Oulu, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Biocenter Oulu, University of Oulu, Oulu</wicri:regionArea><wicri:noRegion>Oulu</wicri:noRegion></affiliation></author><author><name sortKey="Soler Artigas, Maria" sort="Soler Artigas, Maria" uniqKey="Soler Artigas M" first="María" last="Soler Artigas">María Soler Artigas</name><affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester</wicri:regionArea><wicri:noRegion>Leicester</wicri:noRegion></affiliation></author><author><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="aff012"><addr-line>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff013"><addr-line>MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Loth, Daan W" sort="Loth, Daan W" uniqKey="Loth D" first="Daan W." last="Loth">Daan W. Loth</name><affiliation wicri:level="3"><nlm:aff id="aff014"><addr-line>Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Bosse, Yohan" sort="Bosse, Yohan" uniqKey="Bosse Y" first="Yohan" last="Bossé">Yohan Bossé</name><affiliation wicri:level="1"><nlm:aff id="aff015"><addr-line>Institut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Institut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Postma, Dirkje S" sort="Postma, Dirkje S" uniqKey="Postma D" first="Dirkje S." last="Postma">Dirkje S. Postma</name><affiliation wicri:level="4"><nlm:aff id="aff016"><addr-line>Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen</wicri:regionArea><placeName><settlement type="city">Groningue</settlement><region nuts="2" type="province">Groningue (province)</region><settlement type="city">Groningue (ville)</settlement></placeName><orgName type="university">Université de Groningue</orgName></affiliation></author><author><name sortKey="Sin, Don" sort="Sin, Don" uniqKey="Sin D" first="Don" last="Sin">Don Sin</name><affiliation wicri:level="1"><nlm:aff id="aff017"><addr-line>The University of British Columbia Center for Heart Lung Innovation, St-Paul’s Hospital, Vancouver, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>The University of British Columbia Center for Heart Lung Innovation, St-Paul’s Hospital, Vancouver</wicri:regionArea><wicri:noRegion>Vancouver</wicri:noRegion></affiliation></author><author><name sortKey="Thompson, John" sort="Thompson, John" uniqKey="Thompson J" first="John" last="Thompson">John Thompson</name><affiliation wicri:level="1"><nlm:aff id="aff018"><addr-line>Department of Health Sciences, University of Leicester, Leicester, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Health Sciences, University of Leicester, Leicester</wicri:regionArea><wicri:noRegion>Leicester</wicri:noRegion></affiliation></author><author><name sortKey="Demenais, Florence" sort="Demenais, Florence" uniqKey="Demenais F" first="Florence" last="Demenais">Florence Demenais</name><affiliation wicri:level="3"><nlm:aff id="aff019"><addr-line>INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff020"><addr-line>Univ. Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, F-75007, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ. Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, F-75007, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Henderson, John" sort="Henderson, John" uniqKey="Henderson J" first="John" last="Henderson">John Henderson</name><affiliation wicri:level="1"><nlm:aff id="aff021"><addr-line>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Bouzigon, Emmanuelle" sort="Bouzigon, Emmanuelle" uniqKey="Bouzigon E" first="Emmanuelle" last="Bouzigon">Emmanuelle Bouzigon</name><affiliation wicri:level="3"><nlm:aff id="aff019"><addr-line>INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, UMRS-946, Genetic Variation of Human Diseases Unit, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff020"><addr-line>Univ. Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, F-75007, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Univ. Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, F-75007, Paris</wicri:regionArea><placeName><settlement type="city">Paris</settlement><region type="région" nuts="2">Île-de-France</region></placeName></affiliation></author><author><name sortKey="Jarvis, Deborah" sort="Jarvis, Deborah" uniqKey="Jarvis D" first="Deborah" last="Jarvis">Deborah Jarvis</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>MRC-PHE Centre for Environment & Health, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC-PHE Centre for Environment & Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name><affiliation wicri:level="3"><nlm:aff id="aff005"><addr-line>Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>MRC-PHE Centre for Environment & Health, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC-PHE Centre for Environment & Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Biocenter Oulu, University of Oulu, Oulu, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Biocenter Oulu, University of Oulu, Oulu</wicri:regionArea><wicri:noRegion>Oulu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff024"><addr-line>Center for Life Course Epidemiology, Faculty of Medicine, P.O. Box 5000, FI-90014 University of Oulu, Oulu, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Center for Life Course Epidemiology, Faculty of Medicine, P.O. Box 5000, FI-90014 University of Oulu, Oulu</wicri:regionArea><wicri:noRegion>Oulu</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff025"><addr-line>Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. Box 20, FI-90220, Oulu, 90029 OYS, Finland</addr-line></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O. Box 20, FI-90220, Oulu, 90029 OYS</wicri:regionArea><wicri:noRegion>90029 OYS</wicri:noRegion></affiliation></author><author><name sortKey="Burney, Peter" sort="Burney, Peter" uniqKey="Burney P" first="Peter" last="Burney">Peter Burney</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>MRC-PHE Centre for Environment & Health, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC-PHE Centre for Environment & Health, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Female</term><term>Forced Expiratory Volume (genetics)</term><term>Gene Expression Profiling</term><term>Genes, Developmental</term><term>Genetic Association Studies</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Lung (embryology)</term><term>Lung (metabolism)</term><term>Male</term><term>Middle Aged</term><term>Nuclear Receptor Co-Repressor 2 (genetics)</term><term>Nuclear Receptor Co-Repressor 2 (metabolism)</term><term>Organogenesis (genetics)</term><term>Polymorphism, Single Nucleotide</term><term>Quantitative Trait Loci</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de profil d'expression de gènes</term><term>Corépresseur-2 de récepteur nucléaire (génétique)</term><term>Corépresseur-2 de récepteur nucléaire (métabolisme)</term><term>Femelle</term><term>Gènes du développement</term><term>Humains</term><term>Jeune adulte</term><term>Locus de caractère quantitatif</term><term>Mâle</term><term>Organogenèse (génétique)</term><term>Polymorphisme de nucléotide simple</term><term>Poumon (embryologie)</term><term>Poumon (métabolisme)</term><term>Sujet âgé</term><term>Volume expiratoire maximal par seconde (génétique)</term><term>Étude d'association pangénomique</term><term>Études d'associations génétiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Nuclear Receptor Co-Repressor 2</term></keywords><keywords scheme="MESH" qualifier="embryologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="embryology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Forced Expiratory Volume</term><term>Organogenesis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Corépresseur-2 de récepteur nucléaire</term><term>Organogenèse</term><term>Volume expiratoire maximal par seconde</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term><term>Nuclear Receptor Co-Repressor 2</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Corépresseur-2 de récepteur nucléaire</term><term>Poumon</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Female</term><term>Gene Expression Profiling</term><term>Genes, Developmental</term><term>Genetic Association Studies</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Polymorphism, Single Nucleotide</term><term>Quantitative Trait Loci</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Analyse de profil d'expression de gènes</term><term>Femelle</term><term>Gènes du développement</term><term>Humains</term><term>Jeune adulte</term><term>Locus de caractère quantitatif</term><term>Mâle</term><term>Polymorphisme de nucléotide simple</term><term>Sujet âgé</term><term>Étude d'association pangénomique</term><term>Études d'associations génétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title><p>Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes.</p></sec><sec id="sec002"><title>Methods</title><p>Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (<italic>p</italic><0.002; 0.05/25), with a nominal p-value considered as suggestive evidence. For SNPs with evidence of replication, effects on the expression levels of nearby genes in lung tissue were tested in 1,111 lung samples (Lung eQTL consortium), with further functional investigation performed using public epigenomic profiling data (ENCODE).</p></sec><sec id="sec003"><title>Results</title><p><italic>NCOR2</italic>-rs12708369 showed strong replication in children (p = 0.0002), with replication unavailable in adults due to low imputation quality. This intronic variant is in a strong transcriptional enhancer element in lung fibroblasts, but its eQTL effects could not be tested due to low imputation quality in the eQTL dataset. <italic>SERPINE2</italic>-rs6754561 replicated at nominal level in both adults (p = 0.036) and children (p = 0.045), while <italic>WNT16-</italic>rs2707469 replicated at nominal level only in adults (p = 0.026). The eQTL analyses showed association of <italic>WNT16-</italic>rs2707469 with expression levels of the nearby gene <italic>CPED1</italic>. We found no statistically significant eQTL effects for <italic>SERPINE2</italic>-rs6754561.</p></sec><sec id="sec004"><title>Conclusions</title><p>We have identified a new gene, <italic>NCOR2</italic>, in the retinoic acid signalling pathway pointing to a role of vitamin A metabolism in the regulation of FVC. Our findings also support <italic>SERPINE2</italic>, a COPD gene with weak previous evidence of association with FVC, and suggest <italic>WNT16</italic> as a further promising candidate.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Burney, Pg" uniqKey="Burney P">PG Burney</name></author><author><name sortKey="Hooper, R" uniqKey="Hooper R">R Hooper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hegewald, Mj" uniqKey="Hegewald M">MJ Hegewald</name></author><author><name sortKey="Crapo, Ro" uniqKey="Crapo R">RO Crapo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bartley, M" uniqKey="Bartley M">M Bartley</name></author><author><name sortKey="Kelly, Y" uniqKey="Kelly Y">Y Kelly</name></author><author><name sortKey="Sacker, A" uniqKey="Sacker A">A Sacker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Checkley, W" 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sortKey="Binet, R" uniqKey="Binet R">R Binet</name></author><author><name sortKey="Ythier, D" uniqKey="Ythier D">D Ythier</name></author><author><name sortKey="Robles, Ai" uniqKey="Robles A">AI Robles</name></author><author><name sortKey="Collado, M" uniqKey="Collado M">M Collado</name></author><author><name sortKey="Larrieu, D" uniqKey="Larrieu D">D Larrieu</name></author><author><name sortKey="Fonti, C" uniqKey="Fonti C">C Fonti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hancock, Db" uniqKey="Hancock D">DB Hancock</name></author><author><name sortKey="Eijgelsheim, M" uniqKey="Eijgelsheim M">M Eijgelsheim</name></author><author><name sortKey="Wilk, Jb" uniqKey="Wilk J">JB Wilk</name></author><author><name sortKey="Gharib, Sa" uniqKey="Gharib S">SA Gharib</name></author><author><name sortKey="Loehr, Lr" uniqKey="Loehr L">LR Loehr</name></author><author><name sortKey="Marciante, Kd" uniqKey="Marciante K">KD Marciante</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>Canada</li><li>Finlande</li><li>France</li><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Auvergne-Rhône-Alpes</li><li>Grand Londres</li><li>Groningue (province)</li><li>Hollande-Méridionale</li><li>Rhône-Alpes</li><li>Île-de-France</li></region><settlement><li>Grenoble</li><li>Groningue</li><li>Groningue (ville)</li><li>Londres</li><li>Paris</li><li>Rotterdam</li></settlement><orgName><li>Université de Groningue</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Minelli, Cosetta" sort="Minelli, Cosetta" uniqKey="Minelli C" first="Cosetta" last="Minelli">Cosetta Minelli</name></region><name sortKey="Alves, Alexessander Couto" sort="Alves, Alexessander Couto" uniqKey="Alves A" first="Alexessander Couto" last="Alves">Alexessander Couto Alves</name><name sortKey="Amaral, Andre F S" sort="Amaral, Andre F S" uniqKey="Amaral A" first="André F. S." last="Amaral">André F. S. Amaral</name><name sortKey="Amaral, Andre F S" sort="Amaral, Andre F S" uniqKey="Amaral A" first="André F. S." last="Amaral">André F. S. Amaral</name><name sortKey="Burney, Peter" sort="Burney, Peter" uniqKey="Burney P" first="Peter" last="Burney">Peter Burney</name><name sortKey="Burney, Peter" sort="Burney, Peter" uniqKey="Burney P" first="Peter" last="Burney">Peter Burney</name><name sortKey="Dean, Charlotte H" sort="Dean, Charlotte H" uniqKey="Dean C" first="Charlotte H." last="Dean">Charlotte H. Dean</name><name sortKey="Dean, Charlotte H" sort="Dean, Charlotte H" uniqKey="Dean C" first="Charlotte H." last="Dean">Charlotte H. Dean</name><name sortKey="Evans, David M" sort="Evans, David M" uniqKey="Evans D" first="David M." last="Evans">David M. Evans</name><name sortKey="Henderson, John" sort="Henderson, John" uniqKey="Henderson J" first="John" last="Henderson">John Henderson</name><name sortKey="Hind, Matthew" sort="Hind, Matthew" uniqKey="Hind M" first="Matthew" last="Hind">Matthew Hind</name><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name><name sortKey="Jarvis, Deborah" sort="Jarvis, Deborah" uniqKey="Jarvis D" first="Deborah" last="Jarvis">Deborah Jarvis</name><name sortKey="Jarvis, Deborah" sort="Jarvis, Deborah" uniqKey="Jarvis D" first="Deborah" last="Jarvis">Deborah Jarvis</name><name sortKey="Soler Artigas, Maria" sort="Soler Artigas, Maria" uniqKey="Soler Artigas M" first="María" last="Soler Artigas">María Soler Artigas</name><name sortKey="Thompson, John" sort="Thompson, John" uniqKey="Thompson J" first="John" last="Thompson">John Thompson</name></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Siroux, Valerie" sort="Siroux, Valerie" uniqKey="Siroux V" first="Valerie" last="Siroux">Valerie Siroux</name></region><name sortKey="Bouzigon, Emmanuelle" sort="Bouzigon, Emmanuelle" uniqKey="Bouzigon E" first="Emmanuelle" last="Bouzigon">Emmanuelle Bouzigon</name><name sortKey="Bouzigon, Emmanuelle" sort="Bouzigon, Emmanuelle" uniqKey="Bouzigon E" first="Emmanuelle" last="Bouzigon">Emmanuelle Bouzigon</name><name sortKey="Demenais, Florence" sort="Demenais, Florence" uniqKey="Demenais F" first="Florence" last="Demenais">Florence Demenais</name><name sortKey="Demenais, Florence" sort="Demenais, Florence" uniqKey="Demenais F" first="Florence" last="Demenais">Florence Demenais</name><name sortKey="Siroux, Valerie" sort="Siroux, Valerie" uniqKey="Siroux V" first="Valerie" last="Siroux">Valerie Siroux</name><name sortKey="Siroux, Valerie" sort="Siroux, Valerie" uniqKey="Siroux V" first="Valerie" last="Siroux">Valerie Siroux</name></country><country name="Finlande"><noRegion><name sortKey="Huikari, Ville" sort="Huikari, Ville" uniqKey="Huikari V" first="Ville" last="Huikari">Ville Huikari</name></noRegion><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name><name sortKey="J Rvelin, Marjo Riitta" sort="J Rvelin, Marjo Riitta" uniqKey="J Rvelin M" first="Marjo-Riitta" last="J Rvelin">Marjo-Riitta J Rvelin</name></country><country name="Australie"><noRegion><name sortKey="Evans, David M" sort="Evans, David M" uniqKey="Evans D" first="David M." last="Evans">David M. Evans</name></noRegion></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Loth, Daan W" sort="Loth, Daan W" uniqKey="Loth D" first="Daan W." last="Loth">Daan W. Loth</name></region><name sortKey="Postma, Dirkje S" sort="Postma, Dirkje S" uniqKey="Postma D" first="Dirkje S." last="Postma">Dirkje S. Postma</name></country><country name="Canada"><noRegion><name sortKey="Bosse, Yohan" sort="Bosse, Yohan" uniqKey="Bosse Y" first="Yohan" last="Bossé">Yohan Bossé</name></noRegion><name sortKey="Sin, Don" sort="Sin, Don" uniqKey="Sin D" first="Don" last="Sin">Don Sin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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