Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk
Identifieur interne : 000A45 ( Ncbi/Merge ); précédent : 000A44; suivant : 000A46Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk
Auteurs : Emma L. Duncan [Australie] ; Patrick Danoy [Australie] ; John P. Kemp [Royaume-Uni] ; Paul J. Leo [Australie] ; Eugene Mccloskey [Royaume-Uni] ; Geoffrey C. Nicholson [Australie] ; Richard Eastell [Royaume-Uni] ; Richard L. Prince [Australie] ; John A. Eisman [Australie] ; Graeme Jones [Australie] ; Philip N. Sambrook [Australie] ; Ian R. Reid [Nouvelle-Zélande] ; Elaine M. Dennison [Royaume-Uni] ; John Wark [Australie] ; J. Brent Richards [Canada, Royaume-Uni] ; Andre G. Uitterlinden [Pays-Bas] ; Tim D. Spector [Royaume-Uni] ; Chris Esapa [Royaume-Uni] ; Roger D. Cox [Royaume-Uni] ; Steve D. M. Brown [Royaume-Uni] ; Rajesh V. Thakker [Royaume-Uni] ; Kathryn A. Addison [Australie] ; Linda A. Bradbury [Australie] ; Jacqueline R. Center [Australie] ; Cyrus Cooper [Royaume-Uni] ; Catherine Cremin [Australie] ; Karol Estrada [Pays-Bas] ; Dieter Felsenberg [Allemagne] ; Claus-C. Glüer [Allemagne] ; Johanna Hadler [Australie] ; Margaret J. Henry [Australie] ; Albert Hofman [Pays-Bas] ; Mark A. Kotowicz [Australie] ; Joanna Makovey [Australie] ; Sing C. Nguyen [Australie] ; Tuan V. Nguyen [Australie] ; Julie A. Pasco [Australie] ; Karena Pryce [Australie] ; David M. Reid [Royaume-Uni] ; Fernando Rivadeneira [Pays-Bas] ; Christian Roux [France] ; Kari Stefansson [Islande] ; Unnur Styrkarsdottir [Islande] ; Gudmar Thorleifsson [Islande] ; Rumbidzai Tichawangana [Australie] ; David M. Evans [Royaume-Uni] ; Matthew A. Brown [Australie, Royaume-Uni]Source :
- PLoS Genetics [ 1553-7390 ] ; 2011.
Abstract
Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low
bone mineral density (BMD) is a major predisposing factor to fracture and is
known to be highly heritable. Site-, gender-, and age-specific genetic effects
on BMD are thought to be significant, but have largely not been considered in
the design of genome-wide association studies (GWAS) of BMD to date. We report
here a GWAS using a novel study design focusing on women of a specific age
(postmenopausal women, age 55–85 years), with either extreme high or low
hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0,
n = 1055, or −4.0 to −1.5,
n = 900), with replication in cohorts of women drawn from
the general population (n = 20,898). The study replicates
21 of 26 known BMD–associated genes. Additionally, we report suggestive
association of a further six new genetic associations in or around the genes
Url:
DOI: 10.1371/journal.pgen.1001372
PubMed: 21533022
PubMed Central: 3080863
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 002874
- to stream Pmc, to step Curation: 002724
- to stream Pmc, to step Checkpoint: 002309
Links to Exploration step
PMC:3080863Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genome-Wide Association Study Using Extreme Truncate Selection
Identifies Novel Genes Affecting Bone Mineral Density and Fracture
Risk</title><author><name sortKey="Duncan, Emma L" sort="Duncan, Emma L" uniqKey="Duncan E" first="Emma L." last="Duncan">Emma L. Duncan</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Danoy, Patrick" sort="Danoy, Patrick" uniqKey="Danoy P" first="Patrick" last="Danoy">Patrick Danoy</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Kemp, John P" sort="Kemp, John P" uniqKey="Kemp J" first="John P." last="Kemp">John P. Kemp</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Leo, Paul J" sort="Leo, Paul J" uniqKey="Leo P" first="Paul J." last="Leo">Paul J. Leo</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Mccloskey, Eugene" sort="Mccloskey, Eugene" uniqKey="Mccloskey E" first="Eugene" last="Mccloskey">Eugene Mccloskey</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield</wicri:regionArea><wicri:noRegion>Sheffield</wicri:noRegion></affiliation></author><author><name sortKey="Nicholson, Geoffrey C" sort="Nicholson, Geoffrey C" uniqKey="Nicholson G" first="Geoffrey C." last="Nicholson">Geoffrey C. Nicholson</name><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Eastell, Richard" sort="Eastell, Richard" uniqKey="Eastell R" first="Richard" last="Eastell">Richard Eastell</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield</wicri:regionArea><wicri:noRegion>Sheffield</wicri:noRegion></affiliation></author><author><name sortKey="Prince, Richard L" sort="Prince, Richard L" uniqKey="Prince R" first="Richard L." last="Prince">Richard L. Prince</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>School of Medicine and Pharmacology, University of Western Australia, Perth, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medicine and Pharmacology, University of Western Australia, Perth</wicri:regionArea><wicri:noRegion>Perth</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth</wicri:regionArea><wicri:noRegion>Perth</wicri:noRegion></affiliation></author><author><name sortKey="Eisman, John A" sort="Eisman, John A" uniqKey="Eisman J" first="John A." last="Eisman">John A. Eisman</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Garvan Institute of Medical Research, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff8"><addr-line>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Jones, Graeme" sort="Jones, Graeme" uniqKey="Jones G" first="Graeme" last="Jones">Graeme Jones</name><affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Menzies Research Institute, University of Tasmania, Hobart, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Menzies Research Institute, University of Tasmania, Hobart</wicri:regionArea><wicri:noRegion>Hobart</wicri:noRegion></affiliation></author><author><name sortKey="Sambrook, Philip N" sort="Sambrook, Philip N" uniqKey="Sambrook P" first="Philip N." last="Sambrook">Philip N. Sambrook</name><affiliation wicri:level="4"><nlm:aff id="aff10"><addr-line>Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Reid, Ian R" sort="Reid, Ian R" uniqKey="Reid I" first="Ian R." last="Reid">Ian R. Reid</name><affiliation wicri:level="1"><nlm:aff id="aff11"><addr-line>Department of Medicine, University of Auckland, Auckland, New Zealand</addr-line></nlm:aff><country xml:lang="fr">Nouvelle-Zélande</country><wicri:regionArea>Department of Medicine, University of Auckland, Auckland</wicri:regionArea><wicri:noRegion>Auckland</wicri:noRegion></affiliation></author><author><name sortKey="Dennison, Elaine M" sort="Dennison, Elaine M" uniqKey="Dennison E" first="Elaine M." last="Dennison">Elaine M. Dennison</name><affiliation wicri:level="1"><nlm:aff id="aff12"><addr-line>Medical Research Council Lifecourse Epidemiology Unit, Southampton, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Lifecourse Epidemiology Unit, Southampton</wicri:regionArea><wicri:noRegion>Southampton</wicri:noRegion></affiliation></author><author><name sortKey="Wark, John" sort="Wark, John" uniqKey="Wark J" first="John" last="Wark">John Wark</name><affiliation wicri:level="3"><nlm:aff id="aff13"><addr-line>University of Melbourne Department of Medicine and Bone and Mineral Service, Royal Melbourne Hospital, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Melbourne Department of Medicine and Bone and Mineral Service, Royal Melbourne Hospital, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Richards, J Brent" sort="Richards, J Brent" uniqKey="Richards J" first="J. Brent" last="Richards">J. Brent Richards</name><affiliation wicri:level="4"><nlm:aff id="aff14"><addr-line>Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region><settlement type="city">Montréal</settlement></placeName><orgName type="university">Université McGill</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff15"><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's 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="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><affiliation wicri:level="3"><nlm:aff id="aff16"><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine and 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="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D." last="Spector">Tim D. Spector</name><affiliation wicri:level="3"><nlm:aff id="aff15"><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's 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="Esapa, Chris" sort="Esapa, Chris" uniqKey="Esapa C" first="Chris" last="Esapa">Chris Esapa</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire</wicri:regionArea><wicri:noRegion>Oxfordshire</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff18"><addr-line>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Cox, Roger D" sort="Cox, Roger D" uniqKey="Cox R" first="Roger D." last="Cox">Roger D. Cox</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire</wicri:regionArea><wicri:noRegion>Oxfordshire</wicri:noRegion></affiliation></author><author><name sortKey="Brown, Steve D M" sort="Brown, Steve D M" uniqKey="Brown S" first="Steve D. M." last="Brown">Steve D. M. Brown</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire</wicri:regionArea><wicri:noRegion>Oxfordshire</wicri:noRegion></affiliation></author><author><name sortKey="Thakker, Rajesh V" sort="Thakker, Rajesh V" uniqKey="Thakker R" first="Rajesh V." last="Thakker">Rajesh V. Thakker</name><affiliation wicri:level="4"><nlm:aff id="aff18"><addr-line>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Addison, Kathryn A" sort="Addison, Kathryn A" uniqKey="Addison K" first="Kathryn A." last="Addison">Kathryn A. Addison</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Bradbury, Linda A" sort="Bradbury, Linda A" uniqKey="Bradbury L" first="Linda A." last="Bradbury">Linda A. Bradbury</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Center, Jacqueline R" sort="Center, Jacqueline R" uniqKey="Center J" first="Jacqueline R." last="Center">Jacqueline R. Center</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Garvan Institute of Medical Research, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff8"><addr-line>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Cooper, Cyrus" sort="Cooper, Cyrus" uniqKey="Cooper C" first="Cyrus" last="Cooper">Cyrus Cooper</name><affiliation wicri:level="1"><nlm:aff id="aff12"><addr-line>Medical Research Council Lifecourse Epidemiology Unit, Southampton, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Lifecourse Epidemiology Unit, Southampton</wicri:regionArea><wicri:noRegion>Southampton</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff19"><addr-line>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Cremin, Catherine" sort="Cremin, Catherine" uniqKey="Cremin C" first="Catherine" last="Cremin">Catherine Cremin</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Estrada, Karol" sort="Estrada, Karol" uniqKey="Estrada K" first="Karol" last="Estrada">Karol Estrada</name><affiliation wicri:level="3"><nlm:aff id="aff16"><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine and 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="Felsenberg, Dieter" sort="Felsenberg, Dieter" uniqKey="Felsenberg D" first="Dieter" last="Felsenberg">Dieter Felsenberg</name><affiliation wicri:level="3"><nlm:aff id="aff20"><addr-line>Centre of Muscle and Bone Research, Charité – University Medicine Berlin, Campus Benjamin Franklin, Free and Humboldt University, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Centre of Muscle and Bone Research, Charité – University Medicine Berlin, Campus Benjamin Franklin, Free and Humboldt University, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Gluer, Claus C" sort="Gluer, Claus C" uniqKey="Gluer C" first="Claus-C." last="Glüer">Claus-C. Glüer</name><affiliation wicri:level="3"><nlm:aff id="aff21"><addr-line>Medizinische Physik, Klinik für Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Medizinische Physik, Klinik für Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel</wicri:regionArea><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Hadler, Johanna" sort="Hadler, Johanna" uniqKey="Hadler J" first="Johanna" last="Hadler">Johanna Hadler</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Henry, Margaret J" sort="Henry, Margaret J" uniqKey="Henry M" first="Margaret J." last="Henry">Margaret J. Henry</name><affiliation wicri:level="1"><nlm:aff id="aff22"><addr-line>School of Medicine, Deakin University, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medicine, Deakin University, Geelong</wicri:regionArea><wicri:noRegion>Geelong</wicri:noRegion></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation wicri:level="3"><nlm:aff id="aff16"><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine and 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="Kotowicz, Mark A" sort="Kotowicz, Mark A" uniqKey="Kotowicz M" first="Mark A." last="Kotowicz">Mark A. Kotowicz</name><affiliation wicri:level="1"><nlm:aff id="aff23"><addr-line>Department of Endocrinology and Diabetes, Barwon Health, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Endocrinology and Diabetes, Barwon Health, Geelong</wicri:regionArea><wicri:noRegion>Geelong</wicri:noRegion></affiliation></author><author><name sortKey="Makovey, Joanna" sort="Makovey, Joanna" uniqKey="Makovey J" first="Joanna" last="Makovey">Joanna Makovey</name><affiliation wicri:level="4"><nlm:aff id="aff24"><addr-line>Institute of Bone Joint Research, University of Sydney, Royal North Shore Hospital, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute of Bone Joint Research, University of Sydney, Royal North Shore Hospital, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Nguyen, Sing C" sort="Nguyen, Sing C" uniqKey="Nguyen S" first="Sing C." last="Nguyen">Sing C. Nguyen</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Garvan Institute of Medical Research, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff25"><addr-line>School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Public Health and Community Medicine, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Nguyen, Tuan V" sort="Nguyen, Tuan V" uniqKey="Nguyen T" first="Tuan V." last="Nguyen">Tuan V. Nguyen</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Garvan Institute of Medical Research, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff8"><addr-line>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff25"><addr-line>School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Public Health and Community Medicine, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Pasco, Julie A" sort="Pasco, Julie A" uniqKey="Pasco J" first="Julie A." last="Pasco">Julie A. Pasco</name><affiliation wicri:level="1"><nlm:aff id="aff22"><addr-line>School of Medicine, Deakin University, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medicine, Deakin University, Geelong</wicri:regionArea><wicri:noRegion>Geelong</wicri:noRegion></affiliation></author><author><name sortKey="Pryce, Karena" sort="Pryce, Karena" uniqKey="Pryce K" first="Karena" last="Pryce">Karena Pryce</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Reid, David M" sort="Reid, David M" uniqKey="Reid D" first="David M." last="Reid">David M. Reid</name><affiliation wicri:level="1"><nlm:aff id="aff26"><addr-line>Division of Applied Medicine, University of Aberdeen, Aberdeen, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Applied Medicine, University of Aberdeen, Aberdeen</wicri:regionArea><wicri:noRegion>Aberdeen</wicri:noRegion></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation wicri:level="3"><nlm:aff id="aff16"><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine and 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="Roux, Christian" sort="Roux, Christian" uniqKey="Roux C" first="Christian" last="Roux">Christian Roux</name><affiliation wicri:level="3"><nlm:aff id="aff27"><addr-line>Rheumatology Department, AP-HP Cochin Hospital – Paris-Descartes University, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Rheumatology Department, AP-HP Cochin Hospital – Paris-Descartes University, 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></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation wicri:level="1"><nlm:aff id="aff28"><addr-line>deCODE Genetics, Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>deCODE Genetics, Reykjavik</wicri:regionArea><wicri:noRegion>Reykjavik</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff29"><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>University of Iceland, Reykjavik</wicri:regionArea><wicri:noRegion>Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Styrkarsdottir, Unnur" sort="Styrkarsdottir, Unnur" uniqKey="Styrkarsdottir U" first="Unnur" last="Styrkarsdottir">Unnur Styrkarsdottir</name><affiliation wicri:level="1"><nlm:aff id="aff28"><addr-line>deCODE Genetics, Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>deCODE Genetics, Reykjavik</wicri:regionArea><wicri:noRegion>Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation wicri:level="1"><nlm:aff id="aff28"><addr-line>deCODE Genetics, Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>deCODE Genetics, Reykjavik</wicri:regionArea><wicri:noRegion>Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Tichawangana, Rumbidzai" sort="Tichawangana, Rumbidzai" uniqKey="Tichawangana R" first="Rumbidzai" last="Tichawangana">Rumbidzai Tichawangana</name><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></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="aff2"><addr-line>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Brown, Matthew A" sort="Brown, Matthew A" uniqKey="Brown M" first="Matthew A." last="Brown">Matthew A. Brown</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff19"><addr-line>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21533022</idno><idno type="pmc">3080863</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080863</idno><idno type="RBID">PMC:3080863</idno><idno type="doi">10.1371/journal.pgen.1001372</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">002874</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002874</idno><idno type="wicri:Area/Pmc/Curation">002724</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002724</idno><idno type="wicri:Area/Pmc/Checkpoint">002309</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002309</idno><idno type="wicri:Area/Ncbi/Merge">000A45</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-Wide Association Study Using Extreme Truncate Selection
Identifies Novel Genes Affecting Bone Mineral Density and Fracture
Risk</title><author><name sortKey="Duncan, Emma L" sort="Duncan, Emma L" uniqKey="Duncan E" first="Emma L." last="Duncan">Emma L. Duncan</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Danoy, Patrick" sort="Danoy, Patrick" uniqKey="Danoy P" first="Patrick" last="Danoy">Patrick Danoy</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Kemp, John P" sort="Kemp, John P" uniqKey="Kemp J" first="John P." last="Kemp">John P. Kemp</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Leo, Paul J" sort="Leo, Paul J" uniqKey="Leo P" first="Paul J." last="Leo">Paul J. Leo</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Mccloskey, Eugene" sort="Mccloskey, Eugene" uniqKey="Mccloskey E" first="Eugene" last="Mccloskey">Eugene Mccloskey</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield</wicri:regionArea><wicri:noRegion>Sheffield</wicri:noRegion></affiliation></author><author><name sortKey="Nicholson, Geoffrey C" sort="Nicholson, Geoffrey C" uniqKey="Nicholson G" first="Geoffrey C." last="Nicholson">Geoffrey C. Nicholson</name><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Eastell, Richard" sort="Eastell, Richard" uniqKey="Eastell R" first="Richard" last="Eastell">Richard Eastell</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield</wicri:regionArea><wicri:noRegion>Sheffield</wicri:noRegion></affiliation></author><author><name sortKey="Prince, Richard L" sort="Prince, Richard L" uniqKey="Prince R" first="Richard L." last="Prince">Richard L. Prince</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>School of Medicine and Pharmacology, University of Western Australia, Perth, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medicine and Pharmacology, University of Western Australia, Perth</wicri:regionArea><wicri:noRegion>Perth</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth</wicri:regionArea><wicri:noRegion>Perth</wicri:noRegion></affiliation></author><author><name sortKey="Eisman, John A" sort="Eisman, John A" uniqKey="Eisman J" first="John A." last="Eisman">John A. Eisman</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Garvan Institute of Medical Research, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff8"><addr-line>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Jones, Graeme" sort="Jones, Graeme" uniqKey="Jones G" first="Graeme" last="Jones">Graeme Jones</name><affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Menzies Research Institute, University of Tasmania, Hobart, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Menzies Research Institute, University of Tasmania, Hobart</wicri:regionArea><wicri:noRegion>Hobart</wicri:noRegion></affiliation></author><author><name sortKey="Sambrook, Philip N" sort="Sambrook, Philip N" uniqKey="Sambrook P" first="Philip N." last="Sambrook">Philip N. Sambrook</name><affiliation wicri:level="4"><nlm:aff id="aff10"><addr-line>Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Reid, Ian R" sort="Reid, Ian R" uniqKey="Reid I" first="Ian R." last="Reid">Ian R. Reid</name><affiliation wicri:level="1"><nlm:aff id="aff11"><addr-line>Department of Medicine, University of Auckland, Auckland, New Zealand</addr-line></nlm:aff><country xml:lang="fr">Nouvelle-Zélande</country><wicri:regionArea>Department of Medicine, University of Auckland, Auckland</wicri:regionArea><wicri:noRegion>Auckland</wicri:noRegion></affiliation></author><author><name sortKey="Dennison, Elaine M" sort="Dennison, Elaine M" uniqKey="Dennison E" first="Elaine M." last="Dennison">Elaine M. Dennison</name><affiliation wicri:level="1"><nlm:aff id="aff12"><addr-line>Medical Research Council Lifecourse Epidemiology Unit, Southampton, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Lifecourse Epidemiology Unit, Southampton</wicri:regionArea><wicri:noRegion>Southampton</wicri:noRegion></affiliation></author><author><name sortKey="Wark, John" sort="Wark, John" uniqKey="Wark J" first="John" last="Wark">John Wark</name><affiliation wicri:level="3"><nlm:aff id="aff13"><addr-line>University of Melbourne Department of Medicine and Bone and Mineral Service, Royal Melbourne Hospital, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Melbourne Department of Medicine and Bone and Mineral Service, Royal Melbourne Hospital, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Richards, J Brent" sort="Richards, J Brent" uniqKey="Richards J" first="J. Brent" last="Richards">J. Brent Richards</name><affiliation wicri:level="4"><nlm:aff id="aff14"><addr-line>Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region><settlement type="city">Montréal</settlement></placeName><orgName type="university">Université McGill</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff15"><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's 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="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><affiliation wicri:level="3"><nlm:aff id="aff16"><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine and 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="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D." last="Spector">Tim D. Spector</name><affiliation wicri:level="3"><nlm:aff id="aff15"><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's 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="Esapa, Chris" sort="Esapa, Chris" uniqKey="Esapa C" first="Chris" last="Esapa">Chris Esapa</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire</wicri:regionArea><wicri:noRegion>Oxfordshire</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff18"><addr-line>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Cox, Roger D" sort="Cox, Roger D" uniqKey="Cox R" first="Roger D." last="Cox">Roger D. Cox</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire</wicri:regionArea><wicri:noRegion>Oxfordshire</wicri:noRegion></affiliation></author><author><name sortKey="Brown, Steve D M" sort="Brown, Steve D M" uniqKey="Brown S" first="Steve D. M." last="Brown">Steve D. M. Brown</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire</wicri:regionArea><wicri:noRegion>Oxfordshire</wicri:noRegion></affiliation></author><author><name sortKey="Thakker, Rajesh V" sort="Thakker, Rajesh V" uniqKey="Thakker R" first="Rajesh V." last="Thakker">Rajesh V. Thakker</name><affiliation wicri:level="4"><nlm:aff id="aff18"><addr-line>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Addison, Kathryn A" sort="Addison, Kathryn A" uniqKey="Addison K" first="Kathryn A." last="Addison">Kathryn A. Addison</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Bradbury, Linda A" sort="Bradbury, Linda A" uniqKey="Bradbury L" first="Linda A." last="Bradbury">Linda A. Bradbury</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Center, Jacqueline R" sort="Center, Jacqueline R" uniqKey="Center J" first="Jacqueline R." last="Center">Jacqueline R. Center</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Garvan Institute of Medical Research, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff8"><addr-line>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Cooper, Cyrus" sort="Cooper, Cyrus" uniqKey="Cooper C" first="Cyrus" last="Cooper">Cyrus Cooper</name><affiliation wicri:level="1"><nlm:aff id="aff12"><addr-line>Medical Research Council Lifecourse Epidemiology Unit, Southampton, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Lifecourse Epidemiology Unit, Southampton</wicri:regionArea><wicri:noRegion>Southampton</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff19"><addr-line>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author><author><name sortKey="Cremin, Catherine" sort="Cremin, Catherine" uniqKey="Cremin C" first="Catherine" last="Cremin">Catherine Cremin</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Estrada, Karol" sort="Estrada, Karol" uniqKey="Estrada K" first="Karol" last="Estrada">Karol Estrada</name><affiliation wicri:level="3"><nlm:aff id="aff16"><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine and 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="Felsenberg, Dieter" sort="Felsenberg, Dieter" uniqKey="Felsenberg D" first="Dieter" last="Felsenberg">Dieter Felsenberg</name><affiliation wicri:level="3"><nlm:aff id="aff20"><addr-line>Centre of Muscle and Bone Research, Charité – University Medicine Berlin, Campus Benjamin Franklin, Free and Humboldt University, Berlin, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Centre of Muscle and Bone Research, Charité – University Medicine Berlin, Campus Benjamin Franklin, Free and Humboldt University, Berlin</wicri:regionArea><placeName><region type="land" nuts="3">Berlin</region><settlement type="city">Berlin</settlement></placeName></affiliation></author><author><name sortKey="Gluer, Claus C" sort="Gluer, Claus C" uniqKey="Gluer C" first="Claus-C." last="Glüer">Claus-C. Glüer</name><affiliation wicri:level="3"><nlm:aff id="aff21"><addr-line>Medizinische Physik, Klinik für Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Medizinische Physik, Klinik für Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel</wicri:regionArea><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Hadler, Johanna" sort="Hadler, Johanna" uniqKey="Hadler J" first="Johanna" last="Hadler">Johanna Hadler</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Henry, Margaret J" sort="Henry, Margaret J" uniqKey="Henry M" first="Margaret J." last="Henry">Margaret J. Henry</name><affiliation wicri:level="1"><nlm:aff id="aff22"><addr-line>School of Medicine, Deakin University, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medicine, Deakin University, Geelong</wicri:regionArea><wicri:noRegion>Geelong</wicri:noRegion></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation wicri:level="3"><nlm:aff id="aff16"><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine and 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="Kotowicz, Mark A" sort="Kotowicz, Mark A" uniqKey="Kotowicz M" first="Mark A." last="Kotowicz">Mark A. Kotowicz</name><affiliation wicri:level="1"><nlm:aff id="aff23"><addr-line>Department of Endocrinology and Diabetes, Barwon Health, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Endocrinology and Diabetes, Barwon Health, Geelong</wicri:regionArea><wicri:noRegion>Geelong</wicri:noRegion></affiliation></author><author><name sortKey="Makovey, Joanna" sort="Makovey, Joanna" uniqKey="Makovey J" first="Joanna" last="Makovey">Joanna Makovey</name><affiliation wicri:level="4"><nlm:aff id="aff24"><addr-line>Institute of Bone Joint Research, University of Sydney, Royal North Shore Hospital, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Institute of Bone Joint Research, University of Sydney, Royal North Shore Hospital, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Nguyen, Sing C" sort="Nguyen, Sing C" uniqKey="Nguyen S" first="Sing C." last="Nguyen">Sing C. Nguyen</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Garvan Institute of Medical Research, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff25"><addr-line>School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Public Health and Community Medicine, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Nguyen, Tuan V" sort="Nguyen, Tuan V" uniqKey="Nguyen T" first="Tuan V." last="Nguyen">Tuan V. Nguyen</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Garvan Institute of Medical Research, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff8"><addr-line>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff25"><addr-line>School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Public Health and Community Medicine, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Pasco, Julie A" sort="Pasco, Julie A" uniqKey="Pasco J" first="Julie A." last="Pasco">Julie A. Pasco</name><affiliation wicri:level="1"><nlm:aff id="aff22"><addr-line>School of Medicine, Deakin University, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Medicine, Deakin University, Geelong</wicri:regionArea><wicri:noRegion>Geelong</wicri:noRegion></affiliation></author><author><name sortKey="Pryce, Karena" sort="Pryce, Karena" uniqKey="Pryce K" first="Karena" last="Pryce">Karena Pryce</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Reid, David M" sort="Reid, David M" uniqKey="Reid D" first="David M." last="Reid">David M. Reid</name><affiliation wicri:level="1"><nlm:aff id="aff26"><addr-line>Division of Applied Medicine, University of Aberdeen, Aberdeen, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Applied Medicine, University of Aberdeen, Aberdeen</wicri:regionArea><wicri:noRegion>Aberdeen</wicri:noRegion></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation wicri:level="3"><nlm:aff id="aff16"><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Internal Medicine and 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="Roux, Christian" sort="Roux, Christian" uniqKey="Roux C" first="Christian" last="Roux">Christian Roux</name><affiliation wicri:level="3"><nlm:aff id="aff27"><addr-line>Rheumatology Department, AP-HP Cochin Hospital – Paris-Descartes University, Paris, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Rheumatology Department, AP-HP Cochin Hospital – Paris-Descartes University, 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></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation wicri:level="1"><nlm:aff id="aff28"><addr-line>deCODE Genetics, Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>deCODE Genetics, Reykjavik</wicri:regionArea><wicri:noRegion>Reykjavik</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff29"><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>University of Iceland, Reykjavik</wicri:regionArea><wicri:noRegion>Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Styrkarsdottir, Unnur" sort="Styrkarsdottir, Unnur" uniqKey="Styrkarsdottir U" first="Unnur" last="Styrkarsdottir">Unnur Styrkarsdottir</name><affiliation wicri:level="1"><nlm:aff id="aff28"><addr-line>deCODE Genetics, Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>deCODE Genetics, Reykjavik</wicri:regionArea><wicri:noRegion>Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation wicri:level="1"><nlm:aff id="aff28"><addr-line>deCODE Genetics, Reykjavik, Iceland</addr-line></nlm:aff><country xml:lang="fr">Islande</country><wicri:regionArea>deCODE Genetics, Reykjavik</wicri:regionArea><wicri:noRegion>Reykjavik</wicri:noRegion></affiliation></author><author><name sortKey="Tichawangana, Rumbidzai" sort="Tichawangana, Rumbidzai" uniqKey="Tichawangana R" first="Rumbidzai" last="Tichawangana">Rumbidzai Tichawangana</name><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></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="aff2"><addr-line>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol</wicri:regionArea><wicri:noRegion>Bristol</wicri:noRegion></affiliation></author><author><name sortKey="Brown, Matthew A" sort="Brown, Matthew A" uniqKey="Brown M" first="Matthew A." last="Brown">Matthew A. Brown</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff19"><addr-line>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Oxford</settlement></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author></analytic><series><title level="j">PLoS Genetics</title><idno type="ISSN">1553-7390</idno><idno type="eISSN">1553-7404</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low
bone mineral density (BMD) is a major predisposing factor to fracture and is
known to be highly heritable. Site-, gender-, and age-specific genetic effects
on BMD are thought to be significant, but have largely not been considered in
the design of genome-wide association studies (GWAS) of BMD to date. We report
here a GWAS using a novel study design focusing on women of a specific age
(postmenopausal women, age 55–85 years), with either extreme high or low
hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0,
n = 1055, or −4.0 to −1.5,
n = 900), with replication in cohorts of women drawn from
the general population (n = 20,898). The study replicates
21 of 26 known BMD–associated genes. Additionally, we report suggestive
association of a further six new genetic associations in or around the genes
<italic>CLCN7, GALNT3, IBSP, LTBP3, RSPO3</italic>, and
<italic>SOX4</italic>, with replication in two independent datasets. A novel
mouse model with a loss-of-function mutation in <italic>GALNT3</italic> is also
reported, which has high bone mass, supporting the involvement of this gene in
BMD determination. In addition to identifying further genes associated with BMD,
this study confirms the efficiency of extreme-truncate selection designs for
quantitative trait association studies.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Johnell, O" uniqKey="Johnell O">O Johnell</name></author><author><name sortKey="Kanis, Ja" uniqKey="Kanis J">JA Kanis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanis, Ja" uniqKey="Kanis J">JA Kanis</name></author><author><name sortKey="Johnell, O" uniqKey="Johnell O">O Johnell</name></author><author><name sortKey="Oden, A" uniqKey="Oden A">A Oden</name></author><author><name sortKey="Johansson, H" uniqKey="Johansson H">H Johansson</name></author><author><name sortKey="Mccloskey, E" uniqKey="Mccloskey E">E McCloskey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Henry, Mj" uniqKey="Henry M">MJ Henry</name></author><author><name sortKey="Pasco, Ja" uniqKey="Pasco J">JA Pasco</name></author><author><name sortKey="Seeman, E" uniqKey="Seeman E">E Seeman</name></author><author><name sortKey="Nicholson, Gc" uniqKey="Nicholson G">GC Nicholson</name></author><author><name sortKey="Sanders, Km" uniqKey="Sanders K">KM Sanders</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nguyen, Nd" uniqKey="Nguyen N">ND Nguyen</name></author><author><name sortKey="Pongchaiyakul, C" uniqKey="Pongchaiyakul C">C Pongchaiyakul</name></author><author><name sortKey="Center, Jr" uniqKey="Center J">JR Center</name></author><author><name sortKey="Eisman, Ja" uniqKey="Eisman J">JA Eisman</name></author><author><name sortKey="Nguyen, Tv" uniqKey="Nguyen T">TV Nguyen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arden, Nk" uniqKey="Arden N">NK Arden</name></author><author><name sortKey="Baker, J" uniqKey="Baker J">J Baker</name></author><author><name sortKey="Hogg, C" uniqKey="Hogg C">C Hogg</name></author><author><name sortKey="Baan, K" uniqKey="Baan K">K Baan</name></author><author><name sortKey="Spector, Td" uniqKey="Spector T">TD Spector</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arden, Nk" uniqKey="Arden N">NK Arden</name></author><author><name sortKey="Spector, Td" uniqKey="Spector T">TD Spector</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dequeker, J" uniqKey="Dequeker J">J Dequeker</name></author><author><name sortKey="Nijs, J" uniqKey="Nijs J">J Nijs</name></author><author><name sortKey="Verstraeten, A" uniqKey="Verstraeten A">A Verstraeten</name></author><author><name sortKey="Geusens, P" uniqKey="Geusens P">P Geusens</name></author><author><name sortKey="Gevers, G" uniqKey="Gevers G">G Gevers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harris, M" uniqKey="Harris M">M Harris</name></author><author><name sortKey="Nguyen, Tv" uniqKey="Nguyen T">TV Nguyen</name></author><author><name sortKey="Howard, Gm" uniqKey="Howard G">GM Howard</name></author><author><name sortKey="Kelly, Pj" uniqKey="Kelly P">PJ Kelly</name></author><author><name sortKey="Eisman, Ja" uniqKey="Eisman J">JA Eisman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nguyen, Tv" uniqKey="Nguyen T">TV Nguyen</name></author><author><name sortKey="Howard, Gm" uniqKey="Howard G">GM Howard</name></author><author><name sortKey="Kelly, Pj" uniqKey="Kelly P">PJ Kelly</name></author><author><name sortKey="Eisman, Ja" uniqKey="Eisman J">JA Eisman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Duncan, E" uniqKey="Duncan E">E Duncan</name></author><author><name sortKey="Cardon, L" uniqKey="Cardon L">L Cardon</name></author><author><name sortKey="Sinsheimer, J" uniqKey="Sinsheimer J">J Sinsheimer</name></author><author><name sortKey="Wass, J" uniqKey="Wass J">J Wass</name></author><author><name sortKey="Brown, M" uniqKey="Brown M">M Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sigurdsson, G" uniqKey="Sigurdsson G">G Sigurdsson</name></author><author><name sortKey="Halldorsson, Bv" uniqKey="Halldorsson B">BV Halldorsson</name></author><author><name sortKey="Styrkarsdottir, U" uniqKey="Styrkarsdottir U">U Styrkarsdottir</name></author><author><name sortKey="Kristjansson, K" uniqKey="Kristjansson K">K Kristjansson</name></author><author><name sortKey="Stefansson, K" uniqKey="Stefansson K">K Stefansson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flicker, L" uniqKey="Flicker L">L Flicker</name></author><author><name sortKey="Hopper, J" uniqKey="Hopper J">J Hopper</name></author><author><name sortKey="Rodgers, L" uniqKey="Rodgers L">L Rodgers</name></author><author><name sortKey="Kaymakci, B" uniqKey="Kaymakci B">B Kaymakci</name></author><author><name sortKey="Green, R" uniqKey="Green R">R Green</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Duncan, El" uniqKey="Duncan E">EL Duncan</name></author><author><name sortKey="Brown, Ma" uniqKey="Brown M">MA Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naganathan, V" uniqKey="Naganathan V">V Naganathan</name></author><author><name sortKey="Macgregor, A" uniqKey="Macgregor A">A Macgregor</name></author><author><name sortKey="Snieder, H" uniqKey="Snieder H">H Snieder</name></author><author><name sortKey="Nguyen, T" uniqKey="Nguyen T">T Nguyen</name></author><author><name sortKey="Spector, T" uniqKey="Spector T">T Spector</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rivadeneira, F" uniqKey="Rivadeneira F">F Rivadeneira</name></author><author><name sortKey="Styrkarsdottir, U" uniqKey="Styrkarsdottir U">U Styrkarsdottir</name></author><author><name sortKey="Estrada, K" uniqKey="Estrada K">K Estrada</name></author><author><name sortKey="Halldorsson, Bv" uniqKey="Halldorsson B">BV Halldorsson</name></author><author><name sortKey="Hsu, Yh" uniqKey="Hsu Y">YH Hsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Orwoll, Es" uniqKey="Orwoll E">ES Orwoll</name></author><author><name sortKey="Belknap, Jk" uniqKey="Belknap J">JK Belknap</name></author><author><name sortKey="Klein, Rf" uniqKey="Klein R">RF Klein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Henry, Mj" uniqKey="Henry M">MJ Henry</name></author><author><name sortKey="Pasco, Ja" uniqKey="Pasco J">JA Pasco</name></author><author><name sortKey="Nicholson, Gc" uniqKey="Nicholson G">GC Nicholson</name></author><author><name sortKey="Seeman, E" uniqKey="Seeman E">E Seeman</name></author><author><name sortKey="Kotowicz, Ma" uniqKey="Kotowicz M">MA Kotowicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bahlo, M" uniqKey="Bahlo M">M Bahlo</name></author><author><name sortKey="Stankovich, J" uniqKey="Stankovich J">J Stankovich</name></author><author><name sortKey="Danoy, P" uniqKey="Danoy P">P Danoy</name></author><author><name sortKey="Hickey, Pf" uniqKey="Hickey P">PF Hickey</name></author><author><name sortKey="Taylor, Bv" uniqKey="Taylor B">BV Taylor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Richards, Jb" uniqKey="Richards J">JB Richards</name></author><author><name sortKey="Rivadeneira, F" uniqKey="Rivadeneira F">F Rivadeneira</name></author><author><name sortKey="Inouye, M" uniqKey="Inouye M">M Inouye</name></author><author><name sortKey="Pastinen, Tm" uniqKey="Pastinen T">TM Pastinen</name></author><author><name sortKey="Soranzo, N" uniqKey="Soranzo N">N Soranzo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Styrkarsdottir, U" uniqKey="Styrkarsdottir U">U Styrkarsdottir</name></author><author><name sortKey="Halldorsson, Bv" uniqKey="Halldorsson B">BV Halldorsson</name></author><author><name sortKey="Gretarsdottir, S" uniqKey="Gretarsdottir S">S Gretarsdottir</name></author><author><name sortKey="Gudbjartsson, Df" uniqKey="Gudbjartsson D">DF Gudbjartsson</name></author><author><name sortKey="Walters, Gb" uniqKey="Walters G">GB Walters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Styrkarsdottir, U" uniqKey="Styrkarsdottir U">U Styrkarsdottir</name></author><author><name sortKey="Halldorsson, Bv" uniqKey="Halldorsson B">BV Halldorsson</name></author><author><name sortKey="Gretarsdottir, S" uniqKey="Gretarsdottir S">S Gretarsdottir</name></author><author><name sortKey="Gudbjartsson, Df" uniqKey="Gudbjartsson D">DF Gudbjartsson</name></author><author><name sortKey="Walters, Gb" uniqKey="Walters G">GB Walters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shepherd, Ja" uniqKey="Shepherd J">JA Shepherd</name></author><author><name sortKey="Fan, B" uniqKey="Fan B">B Fan</name></author><author><name sortKey="Lu, Y" uniqKey="Lu Y">Y Lu</name></author><author><name sortKey="Lewiecki, Em" uniqKey="Lewiecki E">EM Lewiecki</name></author><author><name sortKey="Miller, P" uniqKey="Miller P">P Miller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raychaudhuri, S" uniqKey="Raychaudhuri S">S Raychaudhuri</name></author><author><name sortKey="Plenge, Rm" uniqKey="Plenge R">RM Plenge</name></author><author><name sortKey="Rossin, Ej" uniqKey="Rossin E">EJ Rossin</name></author><author><name sortKey="Ng, Ac" uniqKey="Ng A">AC Ng</name></author><author><name sortKey="Purcell, Sm" uniqKey="Purcell S">SM Purcell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Price, Al" uniqKey="Price A">AL Price</name></author><author><name sortKey="Weale, Me" uniqKey="Weale M">ME Weale</name></author><author><name sortKey="Patterson, N" uniqKey="Patterson N">N Patterson</name></author><author><name sortKey="Myers, Sr" uniqKey="Myers S">SR Myers</name></author><author><name sortKey="Need, Ac" uniqKey="Need A">AC Need</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Willer, Cj" uniqKey="Willer C">CJ Willer</name></author><author><name sortKey="Sanna, S" uniqKey="Sanna S">S Sanna</name></author><author><name sortKey="Abecasis, Gr" uniqKey="Abecasis G">GR Abecasis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kung, Awc" uniqKey="Kung A">AWC Kung</name></author><author><name sortKey="Xiao, S M" uniqKey="Xiao S">S-M Xiao</name></author><author><name sortKey="Cherny, S" uniqKey="Cherny S">S Cherny</name></author><author><name sortKey="Li, Ghy" uniqKey="Li G">GHY Li</name></author><author><name sortKey="Gao, Y" uniqKey="Gao Y">Y Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Estrada, K" uniqKey="Estrada K">K Estrada</name></author><author><name sortKey="Abuseiris, A" uniqKey="Abuseiris A">A Abuseiris</name></author><author><name sortKey="Grosveld, Fg" uniqKey="Grosveld F">FG Grosveld</name></author><author><name sortKey="Uitterlinden, Ag" uniqKey="Uitterlinden A">AG Uitterlinden</name></author><author><name sortKey="Knoch, Ta" uniqKey="Knoch T">TA Knoch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Willer, Cj" uniqKey="Willer C">CJ Willer</name></author><author><name sortKey="Sanna, S" uniqKey="Sanna S">S Sanna</name></author><author><name sortKey="Jackson, Au" uniqKey="Jackson A">AU Jackson</name></author><author><name sortKey="Scuteri, A" uniqKey="Scuteri A">A Scuteri</name></author><author><name sortKey="Bonnycastle, Ll" uniqKey="Bonnycastle L">LL Bonnycastle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Purcell, S" uniqKey="Purcell S">S Purcell</name></author><author><name sortKey="Cherny, Ss" uniqKey="Cherny S">SS Cherny</name></author><author><name sortKey="Sham, Pc" uniqKey="Sham P">PC Sham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cho, Ys" uniqKey="Cho Y">YS Cho</name></author><author><name sortKey="Go, Mj" uniqKey="Go M">MJ Go</name></author><author><name sortKey="Kim, Yj" uniqKey="Kim Y">YJ Kim</name></author><author><name sortKey="Heo, Jy" uniqKey="Heo J">JY Heo</name></author><author><name sortKey="Oh, Jh" uniqKey="Oh J">JH Oh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiong, Dh" uniqKey="Xiong D">DH Xiong</name></author><author><name sortKey="Liu, Xg" uniqKey="Liu X">XG Liu</name></author><author><name sortKey="Guo, Yf" uniqKey="Guo Y">YF Guo</name></author><author><name sortKey="Tan, Lj" uniqKey="Tan L">LJ Tan</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Timpson, Nj" uniqKey="Timpson N">NJ Timpson</name></author><author><name sortKey="Tobias, Jh" uniqKey="Tobias J">JH Tobias</name></author><author><name sortKey="Richards, Jb" uniqKey="Richards J">JB Richards</name></author><author><name sortKey="Soranzo, N" uniqKey="Soranzo N">N Soranzo</name></author><author><name sortKey="Duncan, El" uniqKey="Duncan E">EL Duncan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Esapa, C" uniqKey="Esapa C">C Esapa</name></author><author><name sortKey="Head, R" uniqKey="Head R">R Head</name></author><author><name sortKey="Chan, E" uniqKey="Chan E">E Chan</name></author><author><name sortKey="Crane, M" uniqKey="Crane M">M Crane</name></author><author><name sortKey="Cheeseman, M" uniqKey="Cheeseman M">M Cheeseman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pettersson, U" uniqKey="Pettersson U">U Pettersson</name></author><author><name sortKey="Albagha, Om" uniqKey="Albagha O">OM Albagha</name></author><author><name sortKey="Mirolo, M" uniqKey="Mirolo M">M Mirolo</name></author><author><name sortKey="Taranta, A" uniqKey="Taranta A">A Taranta</name></author><author><name sortKey="Frattini, A" uniqKey="Frattini A">A Frattini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koller, Dl" uniqKey="Koller D">DL Koller</name></author><author><name sortKey="Ichikawa, S" uniqKey="Ichikawa S">S Ichikawa</name></author><author><name sortKey="Lai, D" uniqKey="Lai D">D Lai</name></author><author><name sortKey="Padgett, Lr" uniqKey="Padgett L">LR Padgett</name></author><author><name sortKey="Doheny, Kf" uniqKey="Doheny K">KF Doheny</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Topaz, O" uniqKey="Topaz O">O Topaz</name></author><author><name sortKey="Shurman, Dl" uniqKey="Shurman D">DL Shurman</name></author><author><name sortKey="Bergman, R" uniqKey="Bergman R">R Bergman</name></author><author><name sortKey="Indelman, M" uniqKey="Indelman M">M Indelman</name></author><author><name sortKey="Ratajczak, P" uniqKey="Ratajczak P">P Ratajczak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frishberg, Y" uniqKey="Frishberg Y">Y Frishberg</name></author><author><name sortKey="Topaz, O" uniqKey="Topaz O">O Topaz</name></author><author><name sortKey="Bergman, R" uniqKey="Bergman R">R Bergman</name></author><author><name sortKey="Behar, D" uniqKey="Behar D">D Behar</name></author><author><name sortKey="Fisher, D" uniqKey="Fisher D">D Fisher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larsson, T" uniqKey="Larsson T">T Larsson</name></author><author><name sortKey="Davis, Si" uniqKey="Davis S">SI Davis</name></author><author><name sortKey="Garringer, Hj" uniqKey="Garringer H">HJ Garringer</name></author><author><name sortKey="Mooney, Sd" uniqKey="Mooney S">SD Mooney</name></author><author><name sortKey="Draman, Ms" uniqKey="Draman M">MS Draman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Urakawa, I" uniqKey="Urakawa I">I Urakawa</name></author><author><name sortKey="Yamazaki, Y" uniqKey="Yamazaki Y">Y Yamazaki</name></author><author><name sortKey="Shimada, T" uniqKey="Shimada T">T Shimada</name></author><author><name sortKey="Iijima, K" uniqKey="Iijima K">K Iijima</name></author><author><name sortKey="Hasegawa, H" uniqKey="Hasegawa H">H Hasegawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawano, K" uniqKey="Kawano K">K Kawano</name></author><author><name sortKey="Ogata, N" uniqKey="Ogata N">N Ogata</name></author><author><name sortKey="Chiano, M" uniqKey="Chiano M">M Chiano</name></author><author><name sortKey="Molloy, H" uniqKey="Molloy H">H Molloy</name></author><author><name sortKey="Kleyn, P" uniqKey="Kleyn P">P Kleyn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ogata, N" uniqKey="Ogata N">N Ogata</name></author><author><name sortKey="Matsumura, Y" uniqKey="Matsumura Y">Y Matsumura</name></author><author><name sortKey="Shiraki, M" uniqKey="Shiraki M">M Shiraki</name></author><author><name sortKey="Kawano, K" uniqKey="Kawano K">K Kawano</name></author><author><name sortKey="Koshizuka, Y" uniqKey="Koshizuka Y">Y Koshizuka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riancho, Ja" uniqKey="Riancho J">JA Riancho</name></author><author><name sortKey="Valero, C" uniqKey="Valero C">C Valero</name></author><author><name sortKey="Hernandez, Jl" uniqKey="Hernandez J">JL Hernandez</name></author><author><name sortKey="Ortiz, F" uniqKey="Ortiz F">F Ortiz</name></author><author><name sortKey="Zarrabeitia, A" uniqKey="Zarrabeitia A">A Zarrabeitia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamada, Y" uniqKey="Yamada Y">Y Yamada</name></author><author><name sortKey="Ando, F" uniqKey="Ando F">F Ando</name></author><author><name sortKey="Niino, N" uniqKey="Niino N">N Niino</name></author><author><name sortKey="Shimokata, H" uniqKey="Shimokata H">H Shimokata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sims, Am" uniqKey="Sims A">AM Sims</name></author><author><name sortKey="Shephard, N" uniqKey="Shephard N">N Shephard</name></author><author><name sortKey="Carter, K" uniqKey="Carter K">K Carter</name></author><author><name sortKey="Doan, T" uniqKey="Doan T">T Doan</name></author><author><name sortKey="Dowling, A" uniqKey="Dowling A">A Dowling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Meurs, Jb" uniqKey="Van Meurs J">JB van Meurs</name></author><author><name sortKey="Rivadeneira, F" uniqKey="Rivadeneira F">F Rivadeneira</name></author><author><name sortKey="Jhamai, M" uniqKey="Jhamai M">M Jhamai</name></author><author><name sortKey="Hugens, W" uniqKey="Hugens W">W Hugens</name></author><author><name sortKey="Hofman, A" uniqKey="Hofman A">A Hofman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Ka" uniqKey="Kim K">KA Kim</name></author><author><name sortKey="Wagle, M" uniqKey="Wagle M">M Wagle</name></author><author><name sortKey="Tran, K" uniqKey="Tran K">K Tran</name></author><author><name sortKey="Zhan, X" uniqKey="Zhan X">X Zhan</name></author><author><name sortKey="Dixon, Ma" uniqKey="Dixon M">MA Dixon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blaydon, Dc" uniqKey="Blaydon D">DC Blaydon</name></author><author><name sortKey="Ishii, Y" uniqKey="Ishii Y">Y Ishii</name></author><author><name sortKey="O Toole, Ea" uniqKey="O Toole E">EA O'Toole</name></author><author><name sortKey="Unsworth, Hc" uniqKey="Unsworth H">HC Unsworth</name></author><author><name sortKey="Teh, Mt" uniqKey="Teh M">MT Teh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aoki, M" uniqKey="Aoki M">M Aoki</name></author><author><name sortKey="Mieda, M" uniqKey="Mieda M">M Mieda</name></author><author><name sortKey="Ikeda, T" uniqKey="Ikeda T">T Ikeda</name></author><author><name sortKey="Hamada, Y" uniqKey="Hamada Y">Y Hamada</name></author><author><name sortKey="Nakamura, H" uniqKey="Nakamura H">H Nakamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trost, Z" uniqKey="Trost Z">Z Trost</name></author><author><name sortKey="Trebse, R" uniqKey="Trebse R">R Trebse</name></author><author><name sortKey="Prezelj, J" uniqKey="Prezelj J">J Prezelj</name></author><author><name sortKey="Komadina, R" uniqKey="Komadina R">R Komadina</name></author><author><name sortKey="Logar, Db" uniqKey="Logar D">DB Logar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malaval, L" uniqKey="Malaval L">L Malaval</name></author><author><name sortKey="Wade Gueye, Nm" uniqKey="Wade Gueye N">NM Wade-Gueye</name></author><author><name sortKey="Boudiffa, M" uniqKey="Boudiffa M">M Boudiffa</name></author><author><name sortKey="Fei, J" uniqKey="Fei J">J Fei</name></author><author><name sortKey="Zirngibl, R" uniqKey="Zirngibl R">R Zirngibl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Noor, A" uniqKey="Noor A">A Noor</name></author><author><name sortKey="Windpassinger, C" uniqKey="Windpassinger C">C Windpassinger</name></author><author><name sortKey="Vitcu, I" uniqKey="Vitcu I">I Vitcu</name></author><author><name sortKey="Orlic, M" uniqKey="Orlic M">M Orlic</name></author><author><name sortKey="Rafiq, Ma" uniqKey="Rafiq M">MA Rafiq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dabovic, B" uniqKey="Dabovic B">B Dabovic</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Colarossi, C" uniqKey="Colarossi C">C Colarossi</name></author><author><name sortKey="Obata, H" uniqKey="Obata H">H Obata</name></author><author><name sortKey="Zambuto, L" uniqKey="Zambuto L">L Zambuto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nissen Meyer, Ls" uniqKey="Nissen Meyer L">LS Nissen-Meyer</name></author><author><name sortKey="Jemtland, R" uniqKey="Jemtland R">R Jemtland</name></author><author><name sortKey="Gautvik, Vt" uniqKey="Gautvik V">VT Gautvik</name></author><author><name sortKey="Pedersen, Me" uniqKey="Pedersen M">ME Pedersen</name></author><author><name sortKey="Paro, R" uniqKey="Paro R">R Paro</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Genet</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Genet</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosgen</journal-id><journal-title-group><journal-title>PLoS Genetics</journal-title></journal-title-group><issn pub-type="ppub">1553-7390</issn><issn pub-type="epub">1553-7404</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21533022</article-id><article-id pub-id-type="pmc">3080863</article-id><article-id pub-id-type="publisher-id">10-PLGE-RA-NV-4180R4</article-id><article-id pub-id-type="doi">10.1371/journal.pgen.1001372</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline"><subject>Diabetes and Endocrinology/Bone and Mineral Metabolism</subject><subject>Genetics and Genomics/Genetics of Disease</subject><subject>Rheumatology/Bone and Mineral Metabolism</subject></subj-group></article-categories><title-group><article-title>Genome-Wide Association Study Using Extreme Truncate Selection
Identifies Novel Genes Affecting Bone Mineral Density and Fracture
Risk</article-title><alt-title alt-title-type="running-head">Genetics of Osteoporosis</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Duncan</surname><given-names>Emma L.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Danoy</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kemp</surname><given-names>John P.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Leo</surname><given-names>Paul J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>McCloskey</surname><given-names>Eugene</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nicholson</surname><given-names>Geoffrey C.</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Eastell</surname><given-names>Richard</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Prince</surname><given-names>Richard L.</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Eisman</surname><given-names>John A.</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jones</surname><given-names>Graeme</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sambrook</surname><given-names>Philip N.</given-names></name><xref ref-type="aff" rid="aff10"><sup>10</sup></xref></contrib><contrib contrib-type="author"><name><surname>Reid</surname><given-names>Ian R.</given-names></name><xref ref-type="aff" rid="aff11"><sup>11</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dennison</surname><given-names>Elaine M.</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wark</surname><given-names>John</given-names></name><xref ref-type="aff" rid="aff13"><sup>13</sup></xref></contrib><contrib contrib-type="author"><name><surname>Richards</surname><given-names>J. Brent</given-names></name><xref ref-type="aff" rid="aff14"><sup>14</sup></xref><xref ref-type="aff" rid="aff15"><sup>15</sup></xref></contrib><contrib contrib-type="author"><name><surname>Uitterlinden</surname><given-names>Andre G.</given-names></name><xref ref-type="aff" rid="aff16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Spector</surname><given-names>Tim D.</given-names></name><xref ref-type="aff" rid="aff15"><sup>15</sup></xref></contrib><contrib contrib-type="author"><name><surname>Esapa</surname><given-names>Chris</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref><xref ref-type="aff" rid="aff18"><sup>18</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cox</surname><given-names>Roger D.</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref></contrib><contrib contrib-type="author"><name><surname>Brown</surname><given-names>Steve D. M.</given-names></name><xref ref-type="aff" rid="aff17"><sup>17</sup></xref></contrib><contrib contrib-type="author"><name><surname>Thakker</surname><given-names>Rajesh V.</given-names></name><xref ref-type="aff" rid="aff18"><sup>18</sup></xref></contrib><contrib contrib-type="author"><name><surname>Addison</surname><given-names>Kathryn A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bradbury</surname><given-names>Linda A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Center</surname><given-names>Jacqueline R.</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cooper</surname><given-names>Cyrus</given-names></name><xref ref-type="aff" rid="aff12"><sup>12</sup></xref><xref ref-type="aff" rid="aff19"><sup>19</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cremin</surname><given-names>Catherine</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Estrada</surname><given-names>Karol</given-names></name><xref ref-type="aff" rid="aff16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Felsenberg</surname><given-names>Dieter</given-names></name><xref ref-type="aff" rid="aff20"><sup>20</sup></xref></contrib><contrib contrib-type="author"><name><surname>Glüer</surname><given-names>Claus-C.</given-names></name><xref ref-type="aff" rid="aff21"><sup>21</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hadler</surname><given-names>Johanna</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Henry</surname><given-names>Margaret J.</given-names></name><xref ref-type="aff" rid="aff22"><sup>22</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hofman</surname><given-names>Albert</given-names></name><xref ref-type="aff" rid="aff16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kotowicz</surname><given-names>Mark A.</given-names></name><xref ref-type="aff" rid="aff23"><sup>23</sup></xref></contrib><contrib contrib-type="author"><name><surname>Makovey</surname><given-names>Joanna</given-names></name><xref ref-type="aff" rid="aff24"><sup>24</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nguyen</surname><given-names>Sing C.</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="aff" rid="aff25"><sup>25</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nguyen</surname><given-names>Tuan V.</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="aff" rid="aff8"><sup>8</sup></xref><xref ref-type="aff" rid="aff25"><sup>25</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pasco</surname><given-names>Julie A.</given-names></name><xref ref-type="aff" rid="aff22"><sup>22</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pryce</surname><given-names>Karena</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Reid</surname><given-names>David M.</given-names></name><xref ref-type="aff" rid="aff26"><sup>26</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rivadeneira</surname><given-names>Fernando</given-names></name><xref ref-type="aff" rid="aff16"><sup>16</sup></xref></contrib><contrib contrib-type="author"><name><surname>Roux</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="aff27"><sup>27</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stefansson</surname><given-names>Kari</given-names></name><xref ref-type="aff" rid="aff28"><sup>28</sup></xref><xref ref-type="aff" rid="aff29"><sup>29</sup></xref></contrib><contrib contrib-type="author"><name><surname>Styrkarsdottir</surname><given-names>Unnur</given-names></name><xref ref-type="aff" rid="aff28"><sup>28</sup></xref></contrib><contrib contrib-type="author"><name><surname>Thorleifsson</surname><given-names>Gudmar</given-names></name><xref ref-type="aff" rid="aff28"><sup>28</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tichawangana</surname><given-names>Rumbidzai</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Evans</surname><given-names>David M.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Brown</surname><given-names>Matthew A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff19"><sup>19</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield, United Kingdom</addr-line></aff><aff id="aff4"><label>4</label><addr-line>The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong, Australia</addr-line></aff><aff id="aff5"><label>5</label><addr-line>School of Medicine and Pharmacology, University of Western Australia, Perth, Australia</addr-line></aff><aff id="aff6"><label>6</label><addr-line>Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Australia</addr-line></aff><aff id="aff7"><label>7</label><addr-line>Garvan Institute of Medical Research, Sydney, Australia</addr-line></aff><aff id="aff8"><label>8</label><addr-line>St. Vincent's Clinical School, St. Vincent's Hospital Campus, University of New South Wales, Sydney, Australia</addr-line></aff><aff id="aff9"><label>9</label><addr-line>Menzies Research Institute, University of Tasmania, Hobart, Australia</addr-line></aff><aff id="aff10"><label>10</label><addr-line>Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, Australia</addr-line></aff><aff id="aff11"><label>11</label><addr-line>Department of Medicine, University of Auckland, Auckland, New Zealand</addr-line></aff><aff id="aff12"><label>12</label><addr-line>Medical Research Council Lifecourse Epidemiology Unit, Southampton, United Kingdom</addr-line></aff><aff id="aff13"><label>13</label><addr-line>University of Melbourne Department of Medicine and Bone and Mineral Service, Royal Melbourne Hospital, Melbourne, Australia</addr-line></aff><aff id="aff14"><label>14</label><addr-line>Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada</addr-line></aff><aff id="aff15"><label>15</label><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></aff><aff id="aff16"><label>16</label><addr-line>Department of Internal Medicine and Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</addr-line></aff><aff id="aff17"><label>17</label><addr-line>Medical Research Council Mammalian Genetics Unit, Harwell Science and Innovation Campus, Harwell, Oxfordshire, United Kingdom</addr-line></aff><aff id="aff18"><label>18</label><addr-line>Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, United Kingdom</addr-line></aff><aff id="aff19"><label>19</label><addr-line>National Institute for Health and Research Biomedical Research Unit, University of Oxford, Oxford, United Kingdom</addr-line></aff><aff id="aff20"><label>20</label><addr-line>Centre of Muscle and Bone Research, Charité – University Medicine Berlin, Campus Benjamin Franklin, Free and Humboldt University, Berlin, Germany</addr-line></aff><aff id="aff21"><label>21</label><addr-line>Medizinische Physik, Klinik für Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany</addr-line></aff><aff id="aff22"><label>22</label><addr-line>School of Medicine, Deakin University, Geelong, Australia</addr-line></aff><aff id="aff23"><label>23</label><addr-line>Department of Endocrinology and Diabetes, Barwon Health, Geelong, Australia</addr-line></aff><aff id="aff24"><label>24</label><addr-line>Institute of Bone Joint Research, University of Sydney, Royal North Shore Hospital, Sydney, Australia</addr-line></aff><aff id="aff25"><label>25</label><addr-line>School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia</addr-line></aff><aff id="aff26"><label>26</label><addr-line>Division of Applied Medicine, University of Aberdeen, Aberdeen, United Kingdom</addr-line></aff><aff id="aff27"><label>27</label><addr-line>Rheumatology Department, AP-HP Cochin Hospital – Paris-Descartes University, Paris, France</addr-line></aff><aff id="aff28"><label>28</label><addr-line>deCODE Genetics, Reykjavik, Iceland</addr-line></aff><aff id="aff29"><label>29</label><addr-line>University of Iceland, Reykjavik, Iceland</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Gibson</surname><given-names>Greg</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">Georgia Institute of Technology, United States of America; David B. Allison, University of Alabama at Birmingham, United States of America</aff><author-notes><corresp id="cor1">* E-mail: <email>matt.brown@uq.edu.au</email></corresp><fn fn-type="con"><p>Conceived and designed the experiments: EL Duncan, P Danoy, E McCloskey, GC
Nicholson, R Eastell, RL Prince, JA Eisman, G Jones, JB Richards, AG
Uitterlinden, TD Spector, C Esapa, RD Cox, SDM Brown, RV Thakker, K Estrada,
F Rivadeneira, K Stafansson, U Styrkarsdottir, G Thorleifsson, MA Brown.
Performed the experiments: EL Duncan, P Danoy, C Esapa, RD Cox, KA Addison,
LA Bradbury, C Cremin, K Estrada, CC Glüer, J Hadler, K Pryce. Analyzed
the data: EL Duncan, P Danoy, JP Kemp, PJ Leo, JB Richards, AG Uitterlinden,
TD Spector, C Esapa, RD Cox, SDM Brown, RV Thakker, K Estrada, CC
Glüer, J Hadler, F Rivadeneira, K Stefansson, U Styrkarsdottir, G
Thorleifsson, DM Evans, MA Brown. Contributed reagents/materials/analysis
tools: EL Duncan, P Danoy, JP Kemp, PJ Leo, E McCloskey, GC Nicholson, R
Eastell, RLPrince, JA Eisman, G Jones, PN Sambrook, IR Reid, EM Dennison, J
Wark, JB Richards, AG Uitterlinden, TD Spector, C Esapa, SDM Brown, RV
Thakker, LA Bradbury, JR Center, C Cooper, K Estrada, D Felsenberg, CC
Glüer, MJ Henry, A Hofman, MA Kotowicz, J Makovey, SC Nguyen, TV
Nguyen, JA Pasco, DM Reid, F Rivadeneira, C Roux, K Stefansson, U
Styrkarsdottir, G Thorleifsson, R Tichawangana, DM Evans, MA Brown. Wrote
the paper: EL Duncan, PJ Leo, DM Evans, MA Brown.</p></fn></author-notes><pub-date pub-type="collection"><month>4</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>21</day><month>4</month><year>2011</year></pub-date><volume>7</volume><issue>4</issue><elocation-id>e1001372</elocation-id><history><date date-type="received"><day>16</day><month>9</month><year>2010</year></date><date date-type="accepted"><day>13</day><month>3</month><year>2011</year></date></history><permissions><copyright-statement>Duncan et al.</copyright-statement><copyright-year>2011</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><abstract><p>Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low
bone mineral density (BMD) is a major predisposing factor to fracture and is
known to be highly heritable. Site-, gender-, and age-specific genetic effects
on BMD are thought to be significant, but have largely not been considered in
the design of genome-wide association studies (GWAS) of BMD to date. We report
here a GWAS using a novel study design focusing on women of a specific age
(postmenopausal women, age 55–85 years), with either extreme high or low
hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0,
n = 1055, or −4.0 to −1.5,
n = 900), with replication in cohorts of women drawn from
the general population (n = 20,898). The study replicates
21 of 26 known BMD–associated genes. Additionally, we report suggestive
association of a further six new genetic associations in or around the genes
<italic>CLCN7, GALNT3, IBSP, LTBP3, RSPO3</italic>, and
<italic>SOX4</italic>, with replication in two independent datasets. A novel
mouse model with a loss-of-function mutation in <italic>GALNT3</italic> is also
reported, which has high bone mass, supporting the involvement of this gene in
BMD determination. In addition to identifying further genes associated with BMD,
this study confirms the efficiency of extreme-truncate selection designs for
quantitative trait association studies.</p></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>Osteoporotic fracture is a major cause of early mortality and morbidity in the
community. To identify genes associated with osteoporosis, we have performed a
genome-wide association study. In order to improve study power and to address
the demographic group of highest risk from osteoporotic fracture, we have used a
unique study design, studying 1,955 postmenopausal women with either extreme
high or low hip bone mineral density. We then confirmed our findings in 20,898
women from the general population. Our study replicated 21 of 26 known
osteoporosis genes, and it identified a further six novel loci (in or nearby
<italic>CLCN7, GALNT3, IBSP, LTBP3, RSPO3</italic>, and
<italic>SOX4</italic>). For one of these loci, <italic>GALTN3</italic>, we
demonstrate in a mouse model that a loss-of-function genetic mutation in
<italic>GALNT3</italic> causes high bone mass. These findings report novel
mechanisms by which osteoporosis can arise, and they significantly add to our
understanding of the aetiology of the disease.</p></abstract><counts><page-count count="10"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Canada</li><li>France</li><li>Islande</li><li>Nouvelle-Zélande</li><li>Pays-Bas</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Berlin</li><li>Grand Londres</li><li>Hollande-Méridionale</li><li>Nouvelle-Galles du Sud</li><li>Oxfordshire</li><li>Québec</li><li>Schleswig-Holstein</li><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Berlin</li><li>Kiel</li><li>Londres</li><li>Melbourne</li><li>Montréal</li><li>Oxford</li><li>Paris</li><li>Rotterdam</li><li>Sydney</li></settlement><orgName><li>Université McGill</li><li>Université d'Oxford</li><li>Université de Melbourne</li><li>Université de Sydney</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Duncan, Emma L" sort="Duncan, Emma L" uniqKey="Duncan E" first="Emma L." last="Duncan">Emma L. Duncan</name></noRegion><name sortKey="Addison, Kathryn A" sort="Addison, Kathryn A" uniqKey="Addison K" first="Kathryn A." last="Addison">Kathryn A. Addison</name><name sortKey="Bradbury, Linda A" sort="Bradbury, Linda A" uniqKey="Bradbury L" first="Linda A." last="Bradbury">Linda A. Bradbury</name><name sortKey="Brown, Matthew A" sort="Brown, Matthew A" uniqKey="Brown M" first="Matthew A." last="Brown">Matthew A. Brown</name><name sortKey="Center, Jacqueline R" sort="Center, Jacqueline R" uniqKey="Center J" first="Jacqueline R." last="Center">Jacqueline R. Center</name><name sortKey="Center, Jacqueline R" sort="Center, Jacqueline R" uniqKey="Center J" first="Jacqueline R." last="Center">Jacqueline R. Center</name><name sortKey="Cremin, Catherine" sort="Cremin, Catherine" uniqKey="Cremin C" first="Catherine" last="Cremin">Catherine Cremin</name><name sortKey="Danoy, Patrick" sort="Danoy, Patrick" uniqKey="Danoy P" first="Patrick" last="Danoy">Patrick Danoy</name><name sortKey="Eisman, John A" sort="Eisman, John A" uniqKey="Eisman J" first="John A." last="Eisman">John A. Eisman</name><name sortKey="Eisman, John A" sort="Eisman, John A" uniqKey="Eisman J" first="John A." last="Eisman">John A. Eisman</name><name sortKey="Hadler, Johanna" sort="Hadler, Johanna" uniqKey="Hadler J" first="Johanna" last="Hadler">Johanna Hadler</name><name sortKey="Henry, Margaret J" sort="Henry, Margaret J" uniqKey="Henry M" first="Margaret J." last="Henry">Margaret J. Henry</name><name sortKey="Jones, Graeme" sort="Jones, Graeme" uniqKey="Jones G" first="Graeme" last="Jones">Graeme Jones</name><name sortKey="Kotowicz, Mark A" sort="Kotowicz, Mark A" uniqKey="Kotowicz M" first="Mark A." last="Kotowicz">Mark A. Kotowicz</name><name sortKey="Leo, Paul J" sort="Leo, Paul J" uniqKey="Leo P" first="Paul J." last="Leo">Paul J. Leo</name><name sortKey="Makovey, Joanna" sort="Makovey, Joanna" uniqKey="Makovey J" first="Joanna" last="Makovey">Joanna Makovey</name><name sortKey="Nguyen, Sing C" sort="Nguyen, Sing C" uniqKey="Nguyen S" first="Sing C." last="Nguyen">Sing C. Nguyen</name><name sortKey="Nguyen, Sing C" sort="Nguyen, Sing C" uniqKey="Nguyen S" first="Sing C." last="Nguyen">Sing C. Nguyen</name><name sortKey="Nguyen, Tuan V" sort="Nguyen, Tuan V" uniqKey="Nguyen T" first="Tuan V." last="Nguyen">Tuan V. Nguyen</name><name sortKey="Nguyen, Tuan V" sort="Nguyen, Tuan V" uniqKey="Nguyen T" first="Tuan V." last="Nguyen">Tuan V. Nguyen</name><name sortKey="Nguyen, Tuan V" sort="Nguyen, Tuan V" uniqKey="Nguyen T" first="Tuan V." last="Nguyen">Tuan V. Nguyen</name><name sortKey="Nicholson, Geoffrey C" sort="Nicholson, Geoffrey C" uniqKey="Nicholson G" first="Geoffrey C." last="Nicholson">Geoffrey C. Nicholson</name><name sortKey="Pasco, Julie A" sort="Pasco, Julie A" uniqKey="Pasco J" first="Julie A." last="Pasco">Julie A. Pasco</name><name sortKey="Prince, Richard L" sort="Prince, Richard L" uniqKey="Prince R" first="Richard L." last="Prince">Richard L. Prince</name><name sortKey="Prince, Richard L" sort="Prince, Richard L" uniqKey="Prince R" first="Richard L." last="Prince">Richard L. Prince</name><name sortKey="Pryce, Karena" sort="Pryce, Karena" uniqKey="Pryce K" first="Karena" last="Pryce">Karena Pryce</name><name sortKey="Sambrook, Philip N" sort="Sambrook, Philip N" uniqKey="Sambrook P" first="Philip N." last="Sambrook">Philip N. Sambrook</name><name sortKey="Tichawangana, Rumbidzai" sort="Tichawangana, Rumbidzai" uniqKey="Tichawangana R" first="Rumbidzai" last="Tichawangana">Rumbidzai Tichawangana</name><name sortKey="Wark, John" sort="Wark, John" uniqKey="Wark J" first="John" last="Wark">John Wark</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Kemp, John P" sort="Kemp, John P" uniqKey="Kemp J" first="John P." last="Kemp">John P. Kemp</name></noRegion><name sortKey="Brown, Matthew A" sort="Brown, Matthew A" uniqKey="Brown M" first="Matthew A." last="Brown">Matthew A. Brown</name><name sortKey="Brown, Steve D M" sort="Brown, Steve D M" uniqKey="Brown S" first="Steve D. M." last="Brown">Steve D. M. Brown</name><name sortKey="Cooper, Cyrus" sort="Cooper, Cyrus" uniqKey="Cooper C" first="Cyrus" last="Cooper">Cyrus Cooper</name><name sortKey="Cooper, Cyrus" sort="Cooper, Cyrus" uniqKey="Cooper C" first="Cyrus" last="Cooper">Cyrus Cooper</name><name sortKey="Cox, Roger D" sort="Cox, Roger D" uniqKey="Cox R" first="Roger D." last="Cox">Roger D. Cox</name><name sortKey="Dennison, Elaine M" sort="Dennison, Elaine M" uniqKey="Dennison E" first="Elaine M." last="Dennison">Elaine M. Dennison</name><name sortKey="Eastell, Richard" sort="Eastell, Richard" uniqKey="Eastell R" first="Richard" last="Eastell">Richard Eastell</name><name sortKey="Esapa, Chris" sort="Esapa, Chris" uniqKey="Esapa C" first="Chris" last="Esapa">Chris Esapa</name><name sortKey="Esapa, Chris" sort="Esapa, Chris" uniqKey="Esapa C" first="Chris" last="Esapa">Chris Esapa</name><name sortKey="Evans, David M" sort="Evans, David M" uniqKey="Evans D" first="David M." last="Evans">David M. Evans</name><name sortKey="Mccloskey, Eugene" sort="Mccloskey, Eugene" uniqKey="Mccloskey E" first="Eugene" last="Mccloskey">Eugene Mccloskey</name><name sortKey="Reid, David M" sort="Reid, David M" uniqKey="Reid D" first="David M." last="Reid">David M. Reid</name><name sortKey="Richards, J Brent" sort="Richards, J Brent" uniqKey="Richards J" first="J. Brent" last="Richards">J. Brent Richards</name><name sortKey="Spector, Tim D" sort="Spector, Tim D" uniqKey="Spector T" first="Tim D." last="Spector">Tim D. Spector</name><name sortKey="Thakker, Rajesh V" sort="Thakker, Rajesh V" uniqKey="Thakker R" first="Rajesh V." last="Thakker">Rajesh V. Thakker</name></country><country name="Nouvelle-Zélande"><noRegion><name sortKey="Reid, Ian R" sort="Reid, Ian R" uniqKey="Reid I" first="Ian R." last="Reid">Ian R. Reid</name></noRegion></country><country name="Canada"><region name="Québec"><name sortKey="Richards, J Brent" sort="Richards, J Brent" uniqKey="Richards J" first="J. Brent" last="Richards">J. Brent Richards</name></region></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name></region><name sortKey="Estrada, Karol" sort="Estrada, Karol" uniqKey="Estrada K" first="Karol" last="Estrada">Karol Estrada</name><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name></country><country name="Allemagne"><region name="Berlin"><name sortKey="Felsenberg, Dieter" sort="Felsenberg, Dieter" uniqKey="Felsenberg D" first="Dieter" last="Felsenberg">Dieter Felsenberg</name></region><name sortKey="Gluer, Claus C" sort="Gluer, Claus C" uniqKey="Gluer C" first="Claus-C." last="Glüer">Claus-C. Glüer</name></country><country name="France"><region name="Île-de-France"><name sortKey="Roux, Christian" sort="Roux, Christian" uniqKey="Roux C" first="Christian" last="Roux">Christian Roux</name></region></country><country name="Islande"><noRegion><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name></noRegion><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><name sortKey="Styrkarsdottir, Unnur" sort="Styrkarsdottir, Unnur" uniqKey="Styrkarsdottir U" first="Unnur" last="Styrkarsdottir">Unnur Styrkarsdottir</name><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A45 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000A45 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:3080863
|texte= Genome-Wide Association Study Using Extreme Truncate Selection
Identifies Novel Genes Affecting Bone Mineral Density and Fracture
Risk
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:21533022" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |