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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Whole-genome sequencing identifies <italic>EN1</italic> as a determinant of bone density and fracture</title><author><name sortKey="Zheng, Hou Feng" sort="Zheng, Hou Feng" uniqKey="Zheng H" first="Hou-Feng" last="Zheng">Hou-Feng Zheng</name><affiliation><nlm:aff id="A1">Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Forgetta, Vincenzo" sort="Forgetta, Vincenzo" uniqKey="Forgetta V" first="Vincenzo" last="Forgetta">Vincenzo Forgetta</name><affiliation><nlm:aff id="A1">Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Hsu, Yi Hsiang" sort="Hsu, Yi Hsiang" uniqKey="Hsu Y" first="Yi-Hsiang" last="Hsu">Yi-Hsiang Hsu</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Broad Institute of MIT and Harvard, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Estrada, Karol" sort="Estrada, Karol" uniqKey="Estrada K" first="Karol" last="Estrada">Karol Estrada</name><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Broad Institute of MIT and Harvard, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Rosello Diez, Alberto" sort="Rosello Diez, Alberto" uniqKey="Rosello Diez A" first="Alberto" last="Rosello-Diez">Alberto Rosello-Diez</name><affiliation><nlm:aff id="A8">Department of Developmental Biology, Sloan-Kettering Institute, New York, NY, USA</nlm:aff></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><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Dahia, Chitra L" sort="Dahia, Chitra L" uniqKey="Dahia C" first="Chitra L" last="Dahia">Chitra L. Dahia</name><affiliation><nlm:aff id="A10">Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Park Min, Kyung Hyun" sort="Park Min, Kyung Hyun" uniqKey="Park Min K" first="Kyung Hyun" last="Park-Min">Kyung Hyun Park-Min</name><affiliation><nlm:aff id="A12">Rheumatology Divison, Hospital for Special Surgery New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Tobias, Jonathan H" sort="Tobias, Jonathan H" uniqKey="Tobias J" first="Jonathan H" last="Tobias">Jonathan H. Tobias</name><affiliation><nlm:aff id="A13">School of Clinical Science, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Kooperberg, Charles" sort="Kooperberg, Charles" uniqKey="Kooperberg C" first="Charles" last="Kooperberg">Charles Kooperberg</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Kleinman, Aaron" sort="Kleinman, Aaron" uniqKey="Kleinman A" first="Aaron" last="Kleinman">Aaron Kleinman</name><affiliation><nlm:aff id="A16">Department of Research, 23andMe, Inc. Mountain View, USA</nlm:aff></affiliation></author><author><name sortKey="Styrkarsdottir, Unnur" sort="Styrkarsdottir, Unnur" uniqKey="Styrkarsdottir U" first="Unnur" last="Styrkarsdottir">Unnur Styrkarsdottir</name><affiliation><nlm:aff id="A17">Department of Population Genomics, deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Liu, Ching Ti" sort="Liu, Ching Ti" uniqKey="Liu C" first="Ching-Ti" last="Liu">Ching-Ti Liu</name><affiliation><nlm:aff id="A18">Department of Biostatistics, Boston University School of Public Health, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Uggla, Charlotta" sort="Uggla, Charlotta" uniqKey="Uggla C" first="Charlotta" last="Uggla">Charlotta Uggla</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Evans, Daniel S" sort="Evans, Daniel S" uniqKey="Evans D" first="Daniel S" last="Evans">Daniel S. Evans</name><affiliation><nlm:aff id="A20">California Pacific Medical Center, San Francisco, USA</nlm:aff></affiliation></author><author><name sortKey="Nielson, Carrie M" sort="Nielson, Carrie M" uniqKey="Nielson C" first="Carrie M" last="Nielson">Carrie M. Nielson</name><affiliation><nlm:aff id="A21">Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Bone & Mineral Unit, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation></author><author><name sortKey="Walter, Klaudia" sort="Walter, Klaudia" uniqKey="Walter K" first="Klaudia" last="Walter">Klaudia Walter</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Pettersson Kymmer, Ulrika" sort="Pettersson Kymmer, Ulrika" uniqKey="Pettersson Kymmer U" first="Ulrika" last="Pettersson-Kymmer">Ulrika Pettersson-Kymmer</name><affiliation><nlm:aff id="A24">Departments of Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Mccarthy, Shane" sort="Mccarthy, Shane" uniqKey="Mccarthy S" first="Shane" last="Mccarthy">Shane Mccarthy</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Joel" sort="Eriksson, Joel" uniqKey="Eriksson J" first="Joel" last="Eriksson">Joel Eriksson</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Kwan, Tony" sort="Kwan, Tony" uniqKey="Kwan T" first="Tony" last="Kwan">Tony Kwan</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Jhamai, Mila" sort="Jhamai, Mila" uniqKey="Jhamai M" first="Mila" last="Jhamai">Mila Jhamai</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Trajanoska, Katerina" sort="Trajanoska, Katerina" uniqKey="Trajanoska K" first="Katerina" last="Trajanoska">Katerina Trajanoska</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Memari, Yasin" sort="Memari, Yasin" uniqKey="Memari Y" first="Yasin" last="Memari">Yasin Memari</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Min, Josine" sort="Min, Josine" uniqKey="Min J" first="Josine" last="Min">Josine Min</name><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Danecek, Petr" sort="Danecek, Petr" uniqKey="Danecek P" first="Petr" last="Danecek">Petr Danecek</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Wilmot, Beth" sort="Wilmot, Beth" uniqKey="Wilmot B" first="Beth" last="Wilmot">Beth Wilmot</name><affiliation><nlm:aff id="A29">Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Department of Medical and Clinical Informatics, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Rui" sort="Li, Rui" uniqKey="Li R" first="Rui" last="Li">Rui Li</name><affiliation><nlm:aff id="A1">Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Chou, Wen Chi" sort="Chou, Wen Chi" uniqKey="Chou W" first="Wen-Chi" last="Chou">Wen-Chi Chou</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Mokry, Lauren E" sort="Mokry, Lauren E" uniqKey="Mokry L" first="Lauren E" last="Mokry">Lauren E. Mokry</name><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Moayyeri, Alireza" sort="Moayyeri, Alireza" uniqKey="Moayyeri A" first="Alireza" last="Moayyeri">Alireza Moayyeri</name><affiliation><nlm:aff id="A31">Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Claussnitzer, Melina" sort="Claussnitzer, Melina" uniqKey="Claussnitzer M" first="Melina" last="Claussnitzer">Melina Claussnitzer</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Broad Institute of MIT and Harvard, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Cheng, Chia Ho" sort="Cheng, Chia Ho" uniqKey="Cheng C" first="Chia-Ho" last="Cheng">Chia-Ho Cheng</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Cheung, Warren" sort="Cheung, Warren" uniqKey="Cheung W" first="Warren" last="Cheung">Warren Cheung</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Human Genetics, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Medina G Mez, Carolina" sort="Medina G Mez, Carolina" uniqKey="Medina G Mez C" first="Carolina" last="Medina-G Mez">Carolina Medina-G Mez</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ge, Bing" sort="Ge, Bing" uniqKey="Ge B" first="Bing" last="Ge">Bing Ge</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Chen, Shu Huang" sort="Chen, Shu Huang" uniqKey="Chen S" first="Shu-Huang" last="Chen">Shu-Huang Chen</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Choi, Kwangbom" sort="Choi, Kwangbom" uniqKey="Choi K" first="Kwangbom" last="Choi">Kwangbom Choi</name><affiliation><nlm:aff id="A35">The Jackson Laboratory, Bar Harbor, Maine, USA</nlm:aff></affiliation></author><author><name sortKey="Oei, Ling" sort="Oei, Ling" uniqKey="Oei L" first="Ling" last="Oei">Ling Oei</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Fraser, James" sort="Fraser, James" uniqKey="Fraser J" first="James" last="Fraser">James Fraser</name><affiliation><nlm:aff id="A36">Department of Biochemistry, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Kraaij, Robert" sort="Kraaij, Robert" uniqKey="Kraaij R" first="Robert" last="Kraaij">Robert Kraaij</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hibbs, Matthew A" sort="Hibbs, Matthew A" uniqKey="Hibbs M" first="Matthew A" last="Hibbs">Matthew A. Hibbs</name><affiliation><nlm:aff id="A35">The Jackson Laboratory, Bar Harbor, Maine, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Department of Computer Science, Trinity University, San Antonio, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Gregson, Celia L" sort="Gregson, Celia L" uniqKey="Gregson C" first="Celia L" last="Gregson">Celia L. Gregson</name><affiliation><nlm:aff id="A38">Musculoskeletal Research Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Medical Research Council Epidemiology Unit, University of Southhampton, Southhampton, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Paquette, Denis" sort="Paquette, Denis" uniqKey="Paquette D" first="Denis" last="Paquette">Denis Paquette</name><affiliation><nlm:aff id="A36">Department of Biochemistry, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wibom, Carl" sort="Wibom, Carl" uniqKey="Wibom C" first="Carl" last="Wibom">Carl Wibom</name><affiliation><nlm:aff id="A40">Department of Radiation Sciences, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Tranah, Gregory J" sort="Tranah, Gregory J" uniqKey="Tranah G" first="Gregory J" last="Tranah">Gregory J. Tranah</name><affiliation><nlm:aff id="A21">Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Bone & Mineral Unit, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation></author><author><name sortKey="Marshall, Mhairi" sort="Marshall, Mhairi" uniqKey="Marshall M" first="Mhairi" last="Marshall">Mhairi Marshall</name><affiliation><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Gardiner, Brooke B" sort="Gardiner, Brooke B" uniqKey="Gardiner B" first="Brooke B" last="Gardiner">Brooke B. Gardiner</name><affiliation><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Cremin, Katie" sort="Cremin, Katie" uniqKey="Cremin K" first="Katie" last="Cremin">Katie Cremin</name><affiliation><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Auer, Paul" sort="Auer, Paul" uniqKey="Auer P" first="Paul" last="Auer">Paul Auer</name><affiliation><nlm:aff id="A41">School of Public Health, University of Wisconsin, Milwaukee, USA</nlm:aff></affiliation></author><author><name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Ring, Sue" sort="Ring, Sue" uniqKey="Ring S" first="Sue" last="Ring">Sue Ring</name><affiliation><nlm:aff id="A42">School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Tung, Joyce Y" sort="Tung, Joyce Y" uniqKey="Tung J" first="Joyce Y" last="Tung">Joyce Y. Tung</name><affiliation><nlm:aff id="A16">Department of Research, 23andMe, Inc. Mountain View, USA</nlm:aff></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation><nlm:aff id="A43">Department of Statistics, deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Enneman, Anke W" sort="Enneman, Anke W" uniqKey="Enneman A" first="Anke W" last="Enneman">Anke W. Enneman</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Schoor, Natasja M" sort="Van Schoor, Natasja M" uniqKey="Van Schoor N" first="Natasja M" last="Van Schoor">Natasja M. Van Schoor</name><affiliation><nlm:aff id="A44">Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="De Groot, Lisette C P G M" sort="De Groot, Lisette C P G M" uniqKey="De Groot L" first="Lisette C. P. G. M." last="De Groot">Lisette C. P. G. M. De Groot</name><affiliation><nlm:aff id="A45">Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Der Velde, Nathalie" sort="Van Der Velde, Nathalie" uniqKey="Van Der Velde N" first="Nathalie" last="Van Der Velde">Nathalie Van Der Velde</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A46">Department of Internal Medicine, Section Geriatrics, Academic Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Melin, Beatrice" sort="Melin, Beatrice" uniqKey="Melin B" first="Beatrice" last="Melin">Beatrice Melin</name><affiliation><nlm:aff id="A40">Department of Radiation Sciences, Umeå University, Umeå, Sweden</nlm:aff></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><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Christiansen, Claus" sort="Christiansen, Claus" uniqKey="Christiansen C" first="Claus" last="Christiansen">Claus Christiansen</name><affiliation><nlm:aff id="A47">Nordic Bioscience, Herlev, Denmark</nlm:aff></affiliation></author><author><name sortKey="Sayers, Adrian" sort="Sayers, Adrian" uniqKey="Sayers A" first="Adrian" last="Sayers">Adrian Sayers</name><affiliation><nlm:aff id="A38">Musculoskeletal Research Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Zhou, Yanhua" sort="Zhou, Yanhua" uniqKey="Zhou Y" first="Yanhua" last="Zhou">Yanhua Zhou</name><affiliation><nlm:aff id="A18">Department of Biostatistics, Boston University School of Public Health, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Calderari, Sophie" sort="Calderari, Sophie" uniqKey="Calderari S" first="Sophie" last="Calderari">Sophie Calderari</name><affiliation><nlm:aff id="A48">Cordeliers Research Centre, INSERM UMRS 1138, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Institute of Cardiometabolism and Nutrition, University Pierre & Marie Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Van Rooij, Jeroen" sort="Van Rooij, Jeroen" uniqKey="Van Rooij J" first="Jeroen" last="Van Rooij">Jeroen Van Rooij</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Carlson, Chris" sort="Carlson, Chris" uniqKey="Carlson C" first="Chris" last="Carlson">Chris Carlson</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Berlivet, Soizik" sort="Berlivet, Soizik" uniqKey="Berlivet S" first="Soizik" last="Berlivet">Soizik Berlivet</name><affiliation><nlm:aff id="A36">Department of Biochemistry, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Dostie, Josee" sort="Dostie, Josee" uniqKey="Dostie J" first="Josée" last="Dostie">Josée Dostie</name><affiliation><nlm:aff id="A36">Department of Biochemistry, McGill University, Montreal, Canada</nlm:aff></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><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Williams, Stephen R" sort="Williams, Stephen R" uniqKey="Williams S" first="Stephen R." last="Williams">Stephen R. Williams</name><affiliation><nlm:aff id="A50">Departments of Medicine (Cardiovascular Medicine), Centre for Public Health Genomics, University of Virginia, Charlottesville, Virginia</nlm:aff></affiliation></author><author><name sortKey="Farber, Charles" sort="Farber, Charles" uniqKey="Farber C" first="Charles" last="Farber">Charles Farber</name><affiliation><nlm:aff id="A50">Departments of Medicine (Cardiovascular Medicine), Centre for Public Health Genomics, University of Virginia, Charlottesville, Virginia</nlm:aff></affiliation></author><author><name sortKey="Grinberg, Daniel" sort="Grinberg, Daniel" uniqKey="Grinberg D" first="Daniel" last="Grinberg">Daniel Grinberg</name><affiliation><nlm:aff id="A51">Department of Genetics, University of Barcelona, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A52">U-720, Centre for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Department of Human Molecular Genetics, The Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Lacroix, Andrea Z" sort="Lacroix, Andrea Z" uniqKey="Lacroix A" first="Andrea Z" last="Lacroix">Andrea Z. Lacroix</name><affiliation><nlm:aff id="A54">Women’s Health Center of Excellence Family Medicine and Public Health, University of California - San Diego, San Diego, USA</nlm:aff></affiliation></author><author><name sortKey="Haessler, Jeff" sort="Haessler, Jeff" uniqKey="Haessler J" first="Jeff" last="Haessler">Jeff Haessler</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I" last="Chasman">Daniel I. Chasman</name><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A55">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Giulianini, Franco" sort="Giulianini, Franco" uniqKey="Giulianini F" first="Franco" last="Giulianini">Franco Giulianini</name><affiliation><nlm:aff id="A55">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Rose, Lynda M" sort="Rose, Lynda M" uniqKey="Rose L" first="Lynda M" last="Rose">Lynda M. Rose</name><affiliation><nlm:aff id="A55">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M" last="Ridker">Paul M. Ridker</name><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A55">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</nlm:aff></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><nlm:aff id="A56">Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A57">School of Medicine Sydney, University of Notre Dame Australia, Sydney, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A58">St. Vincent’s Hospital & Clinical School, NSW University, Sydney, Australia</nlm:aff></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><nlm:aff id="A56">Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A58">St. Vincent’s Hospital & Clinical School, NSW University, Sydney, Australia</nlm:aff></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><nlm:aff id="A56">Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A58">St. Vincent’s Hospital & Clinical School, NSW University, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Nogues, Xavier" sort="Nogues, Xavier" uniqKey="Nogues X" first="Xavier" last="Nogues">Xavier Nogues</name><affiliation><nlm:aff id="A59">Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A60">Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A61">Department of Internal Medicine, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Garcia Giralt, Natalia" sort="Garcia Giralt, Natalia" uniqKey="Garcia Giralt N" first="Natalia" last="Garcia-Giralt">Natalia Garcia-Giralt</name><affiliation><nlm:aff id="A59">Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A60">Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III, Spain</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore L" sort="Launer, Lenore L" uniqKey="Launer L" first="Lenore L" last="Launer">Lenore L. Launer</name><affiliation><nlm:aff id="A62">Neuroepidemiology Section, National Institute on Aging, National Institutes on Health, Bethesda, USA</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmunder" sort="Gudnason, Vilmunder" uniqKey="Gudnason V" first="Vilmunder" last="Gudnason">Vilmunder Gudnason</name><affiliation><nlm:aff id="A63">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Mellstrom, Dan" sort="Mellstrom, Dan" uniqKey="Mellstrom D" first="Dan" last="Mellström">Dan Mellström</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Vandenput, Liesbeth" sort="Vandenput, Liesbeth" uniqKey="Vandenput L" first="Liesbeth" last="Vandenput">Liesbeth Vandenput</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Karlsson, Magnus K" sort="Karlsson, Magnus K" uniqKey="Karlsson M" first="Magnus K" last="Karlsson">Magnus K. Karlsson</name><affiliation><nlm:aff id="A65">Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Department of Orthopaedics, Skåne University Hospital Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Ljunggren, Osten" sort="Ljunggren, Osten" uniqKey="Ljunggren O" first="Östen" last="Ljunggren">Östen Ljunggren</name><affiliation><nlm:aff id="A67">Department of Medical Sciences, University of Uppsala, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="Svensson, Olle" sort="Svensson, Olle" uniqKey="Svensson O" first="Olle" last="Svensson">Olle Svensson</name><affiliation><nlm:aff id="A68">Department of Surgical and Perioperative Sciences, Umeå Unviersity, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Hallmans, Goran" sort="Hallmans, Goran" uniqKey="Hallmans G" first="Göran" last="Hallmans">Göran Hallmans</name><affiliation><nlm:aff id="A25">Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rousseau, Francois" sort="Rousseau, Francois" uniqKey="Rousseau F" first="François" last="Rousseau">François Rousseau</name><affiliation><nlm:aff id="A69">Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec City, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A70">Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec City, Canada</nlm:aff></affiliation></author><author><name sortKey="Giroux, Sylvie" sort="Giroux, Sylvie" uniqKey="Giroux S" first="Sylvie" last="Giroux">Sylvie Giroux</name><affiliation><nlm:aff id="A70">Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec City, Canada</nlm:aff></affiliation></author><author><name sortKey="Bussiere, Johanne" sort="Bussiere, Johanne" uniqKey="Bussiere J" first="Johanne" last="Bussière">Johanne Bussière</name><affiliation><nlm:aff id="A70">Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec City, Canada</nlm:aff></affiliation></author><author><name sortKey="Arp, Pascal P" sort="Arp, Pascal P" uniqKey="Arp P" first="Pascal P" last="Arp">Pascal P. Arp</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Koromani, Fjorda" sort="Koromani, Fjorda" uniqKey="Koromani F" first="Fjorda" last="Koromani">Fjorda Koromani</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></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><nlm:aff id="A71">Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A72">Department of Medicine, University of Western Australia, Perth, Australia</nlm:aff></affiliation></author><author><name sortKey="Lewis, Joshua R" sort="Lewis, Joshua R" uniqKey="Lewis J" first="Joshua R" last="Lewis">Joshua R. Lewis</name><affiliation><nlm:aff id="A71">Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A72">Department of Medicine, University of Western Australia, Perth, Australia</nlm:aff></affiliation></author><author><name sortKey="Langdahl, Bente L" sort="Langdahl, Bente L" uniqKey="Langdahl B" first="Bente L" last="Langdahl">Bente L. Langdahl</name><affiliation><nlm:aff id="A73">Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark</nlm:aff></affiliation></author><author><name sortKey="Hermann, A Pernille" sort="Hermann, A Pernille" uniqKey="Hermann A" first="A Pernille" last="Hermann">A Pernille Hermann</name><affiliation><nlm:aff id="A74">Department of Endocrinology, Odense University Hospital, Odense C, Denmark</nlm:aff></affiliation></author><author><name sortKey="Jensen, Jens Erik B" sort="Jensen, Jens Erik B" uniqKey="Jensen J" first="Jens-Erik B" last="Jensen">Jens-Erik B. Jensen</name><affiliation><nlm:aff id="A75">Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark</nlm:aff></affiliation></author><author><name sortKey="Kaptoge, Stephen" sort="Kaptoge, Stephen" uniqKey="Kaptoge S" first="Stephen" last="Kaptoge">Stephen Kaptoge</name><affiliation><nlm:aff id="A31">Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation><nlm:aff id="A76">Clinical Gerontology Unit, Unviersity of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Reeve, Jonathan" sort="Reeve, Jonathan" uniqKey="Reeve J" first="Jonathan" last="Reeve">Jonathan Reeve</name><affiliation><nlm:aff id="A77">Medicine and Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A78">Institute of Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Formosa, Melissa M" sort="Formosa, Melissa M" uniqKey="Formosa M" first="Melissa M" last="Formosa">Melissa M. Formosa</name><affiliation><nlm:aff id="A79">Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta</nlm:aff></affiliation></author><author><name sortKey="Xuereb Anastasi, Angela" sort="Xuereb Anastasi, Angela" uniqKey="Xuereb Anastasi A" first="Angela" last="Xuereb-Anastasi">Angela Xuereb-Anastasi</name><affiliation><nlm:aff id="A79">Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta</nlm:aff></affiliation></author><author><name sortKey=" Kesson, Kristina" sort=" Kesson, Kristina" uniqKey=" Kesson K" first="Kristina" last=" Kesson">Kristina Kesson</name><affiliation><nlm:aff id="A66">Department of Orthopaedics, Skåne University Hospital Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Mcguigan, Fiona E" sort="Mcguigan, Fiona E" uniqKey="Mcguigan F" first="Fiona E" last="Mcguigan">Fiona E. Mcguigan</name><affiliation><nlm:aff id="A80">Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Garg, Gaurav" sort="Garg, Gaurav" uniqKey="Garg G" first="Gaurav" last="Garg">Gaurav Garg</name><affiliation><nlm:aff id="A80">Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Olmos, Jose M" sort="Olmos, Jose M" uniqKey="Olmos J" first="Jose M" last="Olmos">Jose M. Olmos</name><affiliation><nlm:aff id="A81">Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Department of Internal Medicine, Hospital U.M. Valdecilla- IDIVAL, Santander, Spain</nlm:aff></affiliation></author><author><name sortKey="Zarrabeitia, Maria T" sort="Zarrabeitia, Maria T" uniqKey="Zarrabeitia M" first="Maria T" last="Zarrabeitia">Maria T. Zarrabeitia</name><affiliation><nlm:aff id="A83">Department of Legal Medicine, University of Cantabria, Santander, Spain</nlm:aff></affiliation></author><author><name sortKey="Riancho, Jose A" sort="Riancho, Jose A" uniqKey="Riancho J" first="Jose A" last="Riancho">Jose A. Riancho</name><affiliation><nlm:aff id="A81">Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Department of Internal Medicine, Hospital U.M. Valdecilla- IDIVAL, Santander, Spain</nlm:aff></affiliation></author><author><name sortKey="Ralston, Stuart H" sort="Ralston, Stuart H" uniqKey="Ralston S" first="Stuart H" last="Ralston">Stuart H. Ralston</name><affiliation><nlm:aff id="A84">Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Alonso, Nerea" sort="Alonso, Nerea" uniqKey="Alonso N" first="Nerea" last="Alonso">Nerea Alonso</name><affiliation><nlm:aff id="A84">Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Jiang, Xi" sort="Jiang, Xi" uniqKey="Jiang X" first="Xi" last="Jiang">Xi Jiang</name><affiliation><nlm:aff id="A85">Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA</nlm:aff></affiliation></author><author><name sortKey="Goltzman, David" sort="Goltzman, David" uniqKey="Goltzman D" first="David" last="Goltzman">David Goltzman</name><affiliation><nlm:aff id="A86">Department of Medicine and Physiology, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Pastinen, Tomi" sort="Pastinen, Tomi" uniqKey="Pastinen T" first="Tomi" last="Pastinen">Tomi Pastinen</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Human Genetics, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Grundberg, Elin" sort="Grundberg, Elin" uniqKey="Grundberg E" first="Elin" last="Grundberg">Elin Grundberg</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Human Genetics, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Gauguier, Dominique" sort="Gauguier, Dominique" uniqKey="Gauguier D" first="Dominique" last="Gauguier">Dominique Gauguier</name><affiliation><nlm:aff id="A48">Cordeliers Research Centre, INSERM UMRS 1138, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Institute of Cardiometabolism and Nutrition, University Pierre & Marie Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Orwoll, Eric S" sort="Orwoll, Eric S" uniqKey="Orwoll E" first="Eric S" last="Orwoll">Eric S. Orwoll</name><affiliation><nlm:aff id="A22">Bone & Mineral Unit, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A87">Department of Medicine, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation></author><author><name sortKey="Karasik, David" sort="Karasik, David" uniqKey="Karasik D" first="David" last="Karasik">David Karasik</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Davey Smith, George" sort="Davey Smith, George" uniqKey="Davey Smith G" first="George" last="Davey-Smith">George Davey-Smith</name><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V" last="Smith">Albert V. Smith</name><affiliation><nlm:aff id="A63">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Siggeirsdottir, Kristin" sort="Siggeirsdottir, Kristin" uniqKey="Siggeirsdottir K" first="Kristin" last="Siggeirsdottir">Kristin Siggeirsdottir</name><affiliation><nlm:aff id="A63">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B" last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="A88">Laboratory of Epidemiology, National Institute on Aging, National Institutes of Health, Bethesda, USA</nlm:aff></affiliation></author><author><name sortKey="Zillikens, M Carola" sort="Zillikens, M Carola" uniqKey="Zillikens M" first="M Carola" last="Zillikens">M Carola Zillikens</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Meurs, Joyce Bj" sort="Van Meurs, Joyce Bj" uniqKey="Van Meurs J" first="Joyce Bj" last="Van Meurs">Joyce Bj Van Meurs</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation><nlm:aff id="A17">Department of Population Genomics, deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Maurano, Matthew T" sort="Maurano, Matthew T" uniqKey="Maurano M" first="Matthew T" last="Maurano">Matthew T. Maurano</name><affiliation><nlm:aff id="A89">Department of Genome Sciences, University of Washington, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Timpson, Nicholas J" sort="Timpson, Nicholas J" uniqKey="Timpson N" first="Nicholas J" last="Timpson">Nicholas J. Timpson</name><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Durbin, Richard" sort="Durbin, Richard" uniqKey="Durbin R" first="Richard" last="Durbin">Richard Durbin</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Wilson, Scott G" sort="Wilson, Scott G" uniqKey="Wilson S" first="Scott G" last="Wilson">Scott G. Wilson</name><affiliation><nlm:aff id="A32">Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</nlm:aff></affiliation><affiliation><nlm:aff id="A71">Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A90">School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia</nlm:aff></affiliation></author><author><name sortKey="Ntzani, Evangelia E" sort="Ntzani, Evangelia E" uniqKey="Ntzani E" first="Evangelia E" last="Ntzani">Evangelia E. Ntzani</name><affiliation><nlm:aff id="A91">Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, USA</nlm:aff></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><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A64">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A93">CEO, deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Hinds, David A" sort="Hinds, David A" uniqKey="Hinds D" first="David A" last="Hinds">David A. Hinds</name><affiliation><nlm:aff id="A16">Department of Research, 23andMe, Inc. Mountain View, USA</nlm:aff></affiliation></author><author><name sortKey="Spector, Tim" sort="Spector, Tim" uniqKey="Spector T" first="Tim" last="Spector">Tim Spector</name><affiliation><nlm:aff id="A32">Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Cupples, L Adrienne" sort="Cupples, L Adrienne" uniqKey="Cupples L" first="L Adrienne" last="Cupples">L Adrienne Cupples</name><affiliation><nlm:aff id="A18">Department of Biostatistics, Boston University School of Public Health, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Framingham Heart Study, Framingham, USA</nlm:aff></affiliation></author><author><name sortKey="Ohlsson, Claes" sort="Ohlsson, Claes" uniqKey="Ohlsson C" first="Claes" last="Ohlsson">Claes Ohlsson</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Greenwood, Celia Mt" sort="Greenwood, Celia Mt" uniqKey="Greenwood C" first="Celia Mt" last="Greenwood">Celia Mt Greenwood</name><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Human Genetics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A95">Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Department of Oncology, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Jackson, Rebecca D" sort="Jackson, Rebecca D" uniqKey="Jackson R" first="Rebecca D" last="Jackson">Rebecca D. Jackson</name><affiliation><nlm:aff id="A97">Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio USA</nlm:aff></affiliation></author><author><name sortKey="Rowe, David W" sort="Rowe, David W" uniqKey="Rowe D" first="David W" last="Rowe">David W. Rowe</name><affiliation><nlm:aff id="A85">Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA</nlm:aff></affiliation></author><author><name sortKey="Loomis, Cynthia A" sort="Loomis, Cynthia A" uniqKey="Loomis C" first="Cynthia A" last="Loomis">Cynthia A. Loomis</name><affiliation><nlm:aff id="A98">The Ronald O Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York USA</nlm:aff></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><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Ackert Bicknell, Cheryl L" sort="Ackert Bicknell, Cheryl L" uniqKey="Ackert Bicknell C" first="Cheryl L" last="Ackert-Bicknell">Cheryl L. Ackert-Bicknell</name><affiliation><nlm:aff id="A35">The Jackson Laboratory, Bar Harbor, Maine, USA</nlm:aff></affiliation></author><author><name sortKey="Joyner, Alexandra L" sort="Joyner, Alexandra L" uniqKey="Joyner A" first="Alexandra L" last="Joyner">Alexandra L. Joyner</name><affiliation><nlm:aff id="A8">Department of Developmental Biology, Sloan-Kettering Institute, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Duncan, Emma L" sort="Duncan, Emma L" uniqKey="Duncan E" first="Emma L" last="Duncan">Emma L. Duncan</name><affiliation><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Department of Diabetes and Endocrinology, Royal Brisbane and Women’s Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Kiel, Douglas P" sort="Kiel, Douglas P" uniqKey="Kiel D" first="Douglas P" last="Kiel">Douglas P. Kiel</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A100">Beth Israel Deaconess Medical Center, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></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><nlm:aff id="A1">Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26367794</idno><idno type="pmc">4755714</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755714</idno><idno type="RBID">PMC:4755714</idno><idno type="doi">10.1038/nature14878</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">001D40</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001D40</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Whole-genome sequencing identifies <italic>EN1</italic> as a determinant of bone density and fracture</title><author><name sortKey="Zheng, Hou Feng" sort="Zheng, Hou Feng" uniqKey="Zheng H" first="Hou-Feng" last="Zheng">Hou-Feng Zheng</name><affiliation><nlm:aff id="A1">Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Forgetta, Vincenzo" sort="Forgetta, Vincenzo" uniqKey="Forgetta V" first="Vincenzo" last="Forgetta">Vincenzo Forgetta</name><affiliation><nlm:aff id="A1">Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Hsu, Yi Hsiang" sort="Hsu, Yi Hsiang" uniqKey="Hsu Y" first="Yi-Hsiang" last="Hsu">Yi-Hsiang Hsu</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Broad Institute of MIT and Harvard, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Estrada, Karol" sort="Estrada, Karol" uniqKey="Estrada K" first="Karol" last="Estrada">Karol Estrada</name><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Broad Institute of MIT and Harvard, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Rosello Diez, Alberto" sort="Rosello Diez, Alberto" uniqKey="Rosello Diez A" first="Alberto" last="Rosello-Diez">Alberto Rosello-Diez</name><affiliation><nlm:aff id="A8">Department of Developmental Biology, Sloan-Kettering Institute, New York, NY, USA</nlm:aff></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><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Dahia, Chitra L" sort="Dahia, Chitra L" uniqKey="Dahia C" first="Chitra L" last="Dahia">Chitra L. Dahia</name><affiliation><nlm:aff id="A10">Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Park Min, Kyung Hyun" sort="Park Min, Kyung Hyun" uniqKey="Park Min K" first="Kyung Hyun" last="Park-Min">Kyung Hyun Park-Min</name><affiliation><nlm:aff id="A12">Rheumatology Divison, Hospital for Special Surgery New York, New York, USA</nlm:aff></affiliation></author><author><name sortKey="Tobias, Jonathan H" sort="Tobias, Jonathan H" uniqKey="Tobias J" first="Jonathan H" last="Tobias">Jonathan H. Tobias</name><affiliation><nlm:aff id="A13">School of Clinical Science, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Kooperberg, Charles" sort="Kooperberg, Charles" uniqKey="Kooperberg C" first="Charles" last="Kooperberg">Charles Kooperberg</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Kleinman, Aaron" sort="Kleinman, Aaron" uniqKey="Kleinman A" first="Aaron" last="Kleinman">Aaron Kleinman</name><affiliation><nlm:aff id="A16">Department of Research, 23andMe, Inc. Mountain View, USA</nlm:aff></affiliation></author><author><name sortKey="Styrkarsdottir, Unnur" sort="Styrkarsdottir, Unnur" uniqKey="Styrkarsdottir U" first="Unnur" last="Styrkarsdottir">Unnur Styrkarsdottir</name><affiliation><nlm:aff id="A17">Department of Population Genomics, deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Liu, Ching Ti" sort="Liu, Ching Ti" uniqKey="Liu C" first="Ching-Ti" last="Liu">Ching-Ti Liu</name><affiliation><nlm:aff id="A18">Department of Biostatistics, Boston University School of Public Health, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Uggla, Charlotta" sort="Uggla, Charlotta" uniqKey="Uggla C" first="Charlotta" last="Uggla">Charlotta Uggla</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Evans, Daniel S" sort="Evans, Daniel S" uniqKey="Evans D" first="Daniel S" last="Evans">Daniel S. Evans</name><affiliation><nlm:aff id="A20">California Pacific Medical Center, San Francisco, USA</nlm:aff></affiliation></author><author><name sortKey="Nielson, Carrie M" sort="Nielson, Carrie M" uniqKey="Nielson C" first="Carrie M" last="Nielson">Carrie M. Nielson</name><affiliation><nlm:aff id="A21">Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Bone & Mineral Unit, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation></author><author><name sortKey="Walter, Klaudia" sort="Walter, Klaudia" uniqKey="Walter K" first="Klaudia" last="Walter">Klaudia Walter</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Pettersson Kymmer, Ulrika" sort="Pettersson Kymmer, Ulrika" uniqKey="Pettersson Kymmer U" first="Ulrika" last="Pettersson-Kymmer">Ulrika Pettersson-Kymmer</name><affiliation><nlm:aff id="A24">Departments of Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Mccarthy, Shane" sort="Mccarthy, Shane" uniqKey="Mccarthy S" first="Shane" last="Mccarthy">Shane Mccarthy</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Joel" sort="Eriksson, Joel" uniqKey="Eriksson J" first="Joel" last="Eriksson">Joel Eriksson</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A26">Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Kwan, Tony" sort="Kwan, Tony" uniqKey="Kwan T" first="Tony" last="Kwan">Tony Kwan</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Jhamai, Mila" sort="Jhamai, Mila" uniqKey="Jhamai M" first="Mila" last="Jhamai">Mila Jhamai</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Trajanoska, Katerina" sort="Trajanoska, Katerina" uniqKey="Trajanoska K" first="Katerina" last="Trajanoska">Katerina Trajanoska</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Memari, Yasin" sort="Memari, Yasin" uniqKey="Memari Y" first="Yasin" last="Memari">Yasin Memari</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Min, Josine" sort="Min, Josine" uniqKey="Min J" first="Josine" last="Min">Josine Min</name><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Danecek, Petr" sort="Danecek, Petr" uniqKey="Danecek P" first="Petr" last="Danecek">Petr Danecek</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Wilmot, Beth" sort="Wilmot, Beth" uniqKey="Wilmot B" first="Beth" last="Wilmot">Beth Wilmot</name><affiliation><nlm:aff id="A29">Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Department of Medical and Clinical Informatics, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Rui" sort="Li, Rui" uniqKey="Li R" first="Rui" last="Li">Rui Li</name><affiliation><nlm:aff id="A1">Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Chou, Wen Chi" sort="Chou, Wen Chi" uniqKey="Chou W" first="Wen-Chi" last="Chou">Wen-Chi Chou</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Mokry, Lauren E" sort="Mokry, Lauren E" uniqKey="Mokry L" first="Lauren E" last="Mokry">Lauren E. Mokry</name><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Moayyeri, Alireza" sort="Moayyeri, Alireza" uniqKey="Moayyeri A" first="Alireza" last="Moayyeri">Alireza Moayyeri</name><affiliation><nlm:aff id="A31">Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Claussnitzer, Melina" sort="Claussnitzer, Melina" uniqKey="Claussnitzer M" first="Melina" last="Claussnitzer">Melina Claussnitzer</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Broad Institute of MIT and Harvard, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Cheng, Chia Ho" sort="Cheng, Chia Ho" uniqKey="Cheng C" first="Chia-Ho" last="Cheng">Chia-Ho Cheng</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Cheung, Warren" sort="Cheung, Warren" uniqKey="Cheung W" first="Warren" last="Cheung">Warren Cheung</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Human Genetics, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Medina G Mez, Carolina" sort="Medina G Mez, Carolina" uniqKey="Medina G Mez C" first="Carolina" last="Medina-G Mez">Carolina Medina-G Mez</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ge, Bing" sort="Ge, Bing" uniqKey="Ge B" first="Bing" last="Ge">Bing Ge</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Chen, Shu Huang" sort="Chen, Shu Huang" uniqKey="Chen S" first="Shu-Huang" last="Chen">Shu-Huang Chen</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Choi, Kwangbom" sort="Choi, Kwangbom" uniqKey="Choi K" first="Kwangbom" last="Choi">Kwangbom Choi</name><affiliation><nlm:aff id="A35">The Jackson Laboratory, Bar Harbor, Maine, USA</nlm:aff></affiliation></author><author><name sortKey="Oei, Ling" sort="Oei, Ling" uniqKey="Oei L" first="Ling" last="Oei">Ling Oei</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Fraser, James" sort="Fraser, James" uniqKey="Fraser J" first="James" last="Fraser">James Fraser</name><affiliation><nlm:aff id="A36">Department of Biochemistry, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Kraaij, Robert" sort="Kraaij, Robert" uniqKey="Kraaij R" first="Robert" last="Kraaij">Robert Kraaij</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Hibbs, Matthew A" sort="Hibbs, Matthew A" uniqKey="Hibbs M" first="Matthew A" last="Hibbs">Matthew A. Hibbs</name><affiliation><nlm:aff id="A35">The Jackson Laboratory, Bar Harbor, Maine, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A37">Department of Computer Science, Trinity University, San Antonio, Texas, USA</nlm:aff></affiliation></author><author><name sortKey="Gregson, Celia L" sort="Gregson, Celia L" uniqKey="Gregson C" first="Celia L" last="Gregson">Celia L. Gregson</name><affiliation><nlm:aff id="A38">Musculoskeletal Research Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Medical Research Council Epidemiology Unit, University of Southhampton, Southhampton, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Paquette, Denis" sort="Paquette, Denis" uniqKey="Paquette D" first="Denis" last="Paquette">Denis Paquette</name><affiliation><nlm:aff id="A36">Department of Biochemistry, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wibom, Carl" sort="Wibom, Carl" uniqKey="Wibom C" first="Carl" last="Wibom">Carl Wibom</name><affiliation><nlm:aff id="A40">Department of Radiation Sciences, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Tranah, Gregory J" sort="Tranah, Gregory J" uniqKey="Tranah G" first="Gregory J" last="Tranah">Gregory J. Tranah</name><affiliation><nlm:aff id="A21">Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A22">Bone & Mineral Unit, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation></author><author><name sortKey="Marshall, Mhairi" sort="Marshall, Mhairi" uniqKey="Marshall M" first="Mhairi" last="Marshall">Mhairi Marshall</name><affiliation><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Gardiner, Brooke B" sort="Gardiner, Brooke B" uniqKey="Gardiner B" first="Brooke B" last="Gardiner">Brooke B. Gardiner</name><affiliation><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Cremin, Katie" sort="Cremin, Katie" uniqKey="Cremin K" first="Katie" last="Cremin">Katie Cremin</name><affiliation><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Auer, Paul" sort="Auer, Paul" uniqKey="Auer P" first="Paul" last="Auer">Paul Auer</name><affiliation><nlm:aff id="A41">School of Public Health, University of Wisconsin, Milwaukee, USA</nlm:aff></affiliation></author><author><name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Ring, Sue" sort="Ring, Sue" uniqKey="Ring S" first="Sue" last="Ring">Sue Ring</name><affiliation><nlm:aff id="A42">School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Tung, Joyce Y" sort="Tung, Joyce Y" uniqKey="Tung J" first="Joyce Y" last="Tung">Joyce Y. Tung</name><affiliation><nlm:aff id="A16">Department of Research, 23andMe, Inc. Mountain View, USA</nlm:aff></affiliation></author><author><name sortKey="Thorleifsson, Gudmar" sort="Thorleifsson, Gudmar" uniqKey="Thorleifsson G" first="Gudmar" last="Thorleifsson">Gudmar Thorleifsson</name><affiliation><nlm:aff id="A43">Department of Statistics, deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Enneman, Anke W" sort="Enneman, Anke W" uniqKey="Enneman A" first="Anke W" last="Enneman">Anke W. Enneman</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Schoor, Natasja M" sort="Van Schoor, Natasja M" uniqKey="Van Schoor N" first="Natasja M" last="Van Schoor">Natasja M. Van Schoor</name><affiliation><nlm:aff id="A44">Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="De Groot, Lisette C P G M" sort="De Groot, Lisette C P G M" uniqKey="De Groot L" first="Lisette C. P. G. M." last="De Groot">Lisette C. P. G. M. De Groot</name><affiliation><nlm:aff id="A45">Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Der Velde, Nathalie" sort="Van Der Velde, Nathalie" uniqKey="Van Der Velde N" first="Nathalie" last="Van Der Velde">Nathalie Van Der Velde</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A46">Department of Internal Medicine, Section Geriatrics, Academic Medical Center, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Melin, Beatrice" sort="Melin, Beatrice" uniqKey="Melin B" first="Beatrice" last="Melin">Beatrice Melin</name><affiliation><nlm:aff id="A40">Department of Radiation Sciences, Umeå University, Umeå, Sweden</nlm:aff></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><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Christiansen, Claus" sort="Christiansen, Claus" uniqKey="Christiansen C" first="Claus" last="Christiansen">Claus Christiansen</name><affiliation><nlm:aff id="A47">Nordic Bioscience, Herlev, Denmark</nlm:aff></affiliation></author><author><name sortKey="Sayers, Adrian" sort="Sayers, Adrian" uniqKey="Sayers A" first="Adrian" last="Sayers">Adrian Sayers</name><affiliation><nlm:aff id="A38">Musculoskeletal Research Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Zhou, Yanhua" sort="Zhou, Yanhua" uniqKey="Zhou Y" first="Yanhua" last="Zhou">Yanhua Zhou</name><affiliation><nlm:aff id="A18">Department of Biostatistics, Boston University School of Public Health, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Calderari, Sophie" sort="Calderari, Sophie" uniqKey="Calderari S" first="Sophie" last="Calderari">Sophie Calderari</name><affiliation><nlm:aff id="A48">Cordeliers Research Centre, INSERM UMRS 1138, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Institute of Cardiometabolism and Nutrition, University Pierre & Marie Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Van Rooij, Jeroen" sort="Van Rooij, Jeroen" uniqKey="Van Rooij J" first="Jeroen" last="Van Rooij">Jeroen Van Rooij</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Carlson, Chris" sort="Carlson, Chris" uniqKey="Carlson C" first="Chris" last="Carlson">Chris Carlson</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Berlivet, Soizik" sort="Berlivet, Soizik" uniqKey="Berlivet S" first="Soizik" last="Berlivet">Soizik Berlivet</name><affiliation><nlm:aff id="A36">Department of Biochemistry, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Dostie, Josee" sort="Dostie, Josee" uniqKey="Dostie J" first="Josée" last="Dostie">Josée Dostie</name><affiliation><nlm:aff id="A36">Department of Biochemistry, McGill University, Montreal, Canada</nlm:aff></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><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Williams, Stephen R" sort="Williams, Stephen R" uniqKey="Williams S" first="Stephen R." last="Williams">Stephen R. Williams</name><affiliation><nlm:aff id="A50">Departments of Medicine (Cardiovascular Medicine), Centre for Public Health Genomics, University of Virginia, Charlottesville, Virginia</nlm:aff></affiliation></author><author><name sortKey="Farber, Charles" sort="Farber, Charles" uniqKey="Farber C" first="Charles" last="Farber">Charles Farber</name><affiliation><nlm:aff id="A50">Departments of Medicine (Cardiovascular Medicine), Centre for Public Health Genomics, University of Virginia, Charlottesville, Virginia</nlm:aff></affiliation></author><author><name sortKey="Grinberg, Daniel" sort="Grinberg, Daniel" uniqKey="Grinberg D" first="Daniel" last="Grinberg">Daniel Grinberg</name><affiliation><nlm:aff id="A51">Department of Genetics, University of Barcelona, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A52">U-720, Centre for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A53">Department of Human Molecular Genetics, The Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Lacroix, Andrea Z" sort="Lacroix, Andrea Z" uniqKey="Lacroix A" first="Andrea Z" last="Lacroix">Andrea Z. Lacroix</name><affiliation><nlm:aff id="A54">Women’s Health Center of Excellence Family Medicine and Public Health, University of California - San Diego, San Diego, USA</nlm:aff></affiliation></author><author><name sortKey="Haessler, Jeff" sort="Haessler, Jeff" uniqKey="Haessler J" first="Jeff" last="Haessler">Jeff Haessler</name><affiliation><nlm:aff id="A15">Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I" last="Chasman">Daniel I. Chasman</name><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A55">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Giulianini, Franco" sort="Giulianini, Franco" uniqKey="Giulianini F" first="Franco" last="Giulianini">Franco Giulianini</name><affiliation><nlm:aff id="A55">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Rose, Lynda M" sort="Rose, Lynda M" uniqKey="Rose L" first="Lynda M" last="Rose">Lynda M. Rose</name><affiliation><nlm:aff id="A55">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M" last="Ridker">Paul M. Ridker</name><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A55">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</nlm:aff></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><nlm:aff id="A56">Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A57">School of Medicine Sydney, University of Notre Dame Australia, Sydney, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A58">St. Vincent’s Hospital & Clinical School, NSW University, Sydney, Australia</nlm:aff></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><nlm:aff id="A56">Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A58">St. Vincent’s Hospital & Clinical School, NSW University, Sydney, Australia</nlm:aff></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><nlm:aff id="A56">Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A58">St. Vincent’s Hospital & Clinical School, NSW University, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Nogues, Xavier" sort="Nogues, Xavier" uniqKey="Nogues X" first="Xavier" last="Nogues">Xavier Nogues</name><affiliation><nlm:aff id="A59">Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A60">Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A61">Department of Internal Medicine, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Garcia Giralt, Natalia" sort="Garcia Giralt, Natalia" uniqKey="Garcia Giralt N" first="Natalia" last="Garcia-Giralt">Natalia Garcia-Giralt</name><affiliation><nlm:aff id="A59">Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A60">Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III, Spain</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore L" sort="Launer, Lenore L" uniqKey="Launer L" first="Lenore L" last="Launer">Lenore L. Launer</name><affiliation><nlm:aff id="A62">Neuroepidemiology Section, National Institute on Aging, National Institutes on Health, Bethesda, USA</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmunder" sort="Gudnason, Vilmunder" uniqKey="Gudnason V" first="Vilmunder" last="Gudnason">Vilmunder Gudnason</name><affiliation><nlm:aff id="A63">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Mellstrom, Dan" sort="Mellstrom, Dan" uniqKey="Mellstrom D" first="Dan" last="Mellström">Dan Mellström</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Vandenput, Liesbeth" sort="Vandenput, Liesbeth" uniqKey="Vandenput L" first="Liesbeth" last="Vandenput">Liesbeth Vandenput</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Karlsson, Magnus K" sort="Karlsson, Magnus K" uniqKey="Karlsson M" first="Magnus K" last="Karlsson">Magnus K. Karlsson</name><affiliation><nlm:aff id="A65">Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A66">Department of Orthopaedics, Skåne University Hospital Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Ljunggren, Osten" sort="Ljunggren, Osten" uniqKey="Ljunggren O" first="Östen" last="Ljunggren">Östen Ljunggren</name><affiliation><nlm:aff id="A67">Department of Medical Sciences, University of Uppsala, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="Svensson, Olle" sort="Svensson, Olle" uniqKey="Svensson O" first="Olle" last="Svensson">Olle Svensson</name><affiliation><nlm:aff id="A68">Department of Surgical and Perioperative Sciences, Umeå Unviersity, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Hallmans, Goran" sort="Hallmans, Goran" uniqKey="Hallmans G" first="Göran" last="Hallmans">Göran Hallmans</name><affiliation><nlm:aff id="A25">Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rousseau, Francois" sort="Rousseau, Francois" uniqKey="Rousseau F" first="François" last="Rousseau">François Rousseau</name><affiliation><nlm:aff id="A69">Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec City, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A70">Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec City, Canada</nlm:aff></affiliation></author><author><name sortKey="Giroux, Sylvie" sort="Giroux, Sylvie" uniqKey="Giroux S" first="Sylvie" last="Giroux">Sylvie Giroux</name><affiliation><nlm:aff id="A70">Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec City, Canada</nlm:aff></affiliation></author><author><name sortKey="Bussiere, Johanne" sort="Bussiere, Johanne" uniqKey="Bussiere J" first="Johanne" last="Bussière">Johanne Bussière</name><affiliation><nlm:aff id="A70">Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec City, Canada</nlm:aff></affiliation></author><author><name sortKey="Arp, Pascal P" sort="Arp, Pascal P" uniqKey="Arp P" first="Pascal P" last="Arp">Pascal P. Arp</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Koromani, Fjorda" sort="Koromani, Fjorda" uniqKey="Koromani F" first="Fjorda" last="Koromani">Fjorda Koromani</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></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><nlm:aff id="A71">Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A72">Department of Medicine, University of Western Australia, Perth, Australia</nlm:aff></affiliation></author><author><name sortKey="Lewis, Joshua R" sort="Lewis, Joshua R" uniqKey="Lewis J" first="Joshua R" last="Lewis">Joshua R. Lewis</name><affiliation><nlm:aff id="A71">Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A72">Department of Medicine, University of Western Australia, Perth, Australia</nlm:aff></affiliation></author><author><name sortKey="Langdahl, Bente L" sort="Langdahl, Bente L" uniqKey="Langdahl B" first="Bente L" last="Langdahl">Bente L. Langdahl</name><affiliation><nlm:aff id="A73">Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark</nlm:aff></affiliation></author><author><name sortKey="Hermann, A Pernille" sort="Hermann, A Pernille" uniqKey="Hermann A" first="A Pernille" last="Hermann">A Pernille Hermann</name><affiliation><nlm:aff id="A74">Department of Endocrinology, Odense University Hospital, Odense C, Denmark</nlm:aff></affiliation></author><author><name sortKey="Jensen, Jens Erik B" sort="Jensen, Jens Erik B" uniqKey="Jensen J" first="Jens-Erik B" last="Jensen">Jens-Erik B. Jensen</name><affiliation><nlm:aff id="A75">Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark</nlm:aff></affiliation></author><author><name sortKey="Kaptoge, Stephen" sort="Kaptoge, Stephen" uniqKey="Kaptoge S" first="Stephen" last="Kaptoge">Stephen Kaptoge</name><affiliation><nlm:aff id="A31">Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation><nlm:aff id="A76">Clinical Gerontology Unit, Unviersity of Cambridge, Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Reeve, Jonathan" sort="Reeve, Jonathan" uniqKey="Reeve J" first="Jonathan" last="Reeve">Jonathan Reeve</name><affiliation><nlm:aff id="A77">Medicine and Public Health and Primary Care, University of Cambridge, Cambridge, UK</nlm:aff></affiliation><affiliation><nlm:aff id="A78">Institute of Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Formosa, Melissa M" sort="Formosa, Melissa M" uniqKey="Formosa M" first="Melissa M" last="Formosa">Melissa M. Formosa</name><affiliation><nlm:aff id="A79">Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta</nlm:aff></affiliation></author><author><name sortKey="Xuereb Anastasi, Angela" sort="Xuereb Anastasi, Angela" uniqKey="Xuereb Anastasi A" first="Angela" last="Xuereb-Anastasi">Angela Xuereb-Anastasi</name><affiliation><nlm:aff id="A79">Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta</nlm:aff></affiliation></author><author><name sortKey=" Kesson, Kristina" sort=" Kesson, Kristina" uniqKey=" Kesson K" first="Kristina" last=" Kesson">Kristina Kesson</name><affiliation><nlm:aff id="A66">Department of Orthopaedics, Skåne University Hospital Malmö, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="A80">Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Mcguigan, Fiona E" sort="Mcguigan, Fiona E" uniqKey="Mcguigan F" first="Fiona E" last="Mcguigan">Fiona E. Mcguigan</name><affiliation><nlm:aff id="A80">Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Garg, Gaurav" sort="Garg, Gaurav" uniqKey="Garg G" first="Gaurav" last="Garg">Gaurav Garg</name><affiliation><nlm:aff id="A80">Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden</nlm:aff></affiliation></author><author><name sortKey="Olmos, Jose M" sort="Olmos, Jose M" uniqKey="Olmos J" first="Jose M" last="Olmos">Jose M. Olmos</name><affiliation><nlm:aff id="A81">Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Department of Internal Medicine, Hospital U.M. Valdecilla- IDIVAL, Santander, Spain</nlm:aff></affiliation></author><author><name sortKey="Zarrabeitia, Maria T" sort="Zarrabeitia, Maria T" uniqKey="Zarrabeitia M" first="Maria T" last="Zarrabeitia">Maria T. Zarrabeitia</name><affiliation><nlm:aff id="A83">Department of Legal Medicine, University of Cantabria, Santander, Spain</nlm:aff></affiliation></author><author><name sortKey="Riancho, Jose A" sort="Riancho, Jose A" uniqKey="Riancho J" first="Jose A" last="Riancho">Jose A. Riancho</name><affiliation><nlm:aff id="A81">Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="A82">Department of Internal Medicine, Hospital U.M. Valdecilla- IDIVAL, Santander, Spain</nlm:aff></affiliation></author><author><name sortKey="Ralston, Stuart H" sort="Ralston, Stuart H" uniqKey="Ralston S" first="Stuart H" last="Ralston">Stuart H. Ralston</name><affiliation><nlm:aff id="A84">Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Alonso, Nerea" sort="Alonso, Nerea" uniqKey="Alonso N" first="Nerea" last="Alonso">Nerea Alonso</name><affiliation><nlm:aff id="A84">Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK</nlm:aff></affiliation></author><author><name sortKey="Jiang, Xi" sort="Jiang, Xi" uniqKey="Jiang X" first="Xi" last="Jiang">Xi Jiang</name><affiliation><nlm:aff id="A85">Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA</nlm:aff></affiliation></author><author><name sortKey="Goltzman, David" sort="Goltzman, David" uniqKey="Goltzman D" first="David" last="Goltzman">David Goltzman</name><affiliation><nlm:aff id="A86">Department of Medicine and Physiology, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Pastinen, Tomi" sort="Pastinen, Tomi" uniqKey="Pastinen T" first="Tomi" last="Pastinen">Tomi Pastinen</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Human Genetics, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Grundberg, Elin" sort="Grundberg, Elin" uniqKey="Grundberg E" first="Elin" last="Grundberg">Elin Grundberg</name><affiliation><nlm:aff id="A27">McGill University and Genome Quebec Innovation Centre, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Human Genetics, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Gauguier, Dominique" sort="Gauguier, Dominique" uniqKey="Gauguier D" first="Dominique" last="Gauguier">Dominique Gauguier</name><affiliation><nlm:aff id="A48">Cordeliers Research Centre, INSERM UMRS 1138, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A49">Institute of Cardiometabolism and Nutrition, University Pierre & Marie Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Orwoll, Eric S" sort="Orwoll, Eric S" uniqKey="Orwoll E" first="Eric S" last="Orwoll">Eric S. Orwoll</name><affiliation><nlm:aff id="A22">Bone & Mineral Unit, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A87">Department of Medicine, Oregon Health & Science University, Portland, USA</nlm:aff></affiliation></author><author><name sortKey="Karasik, David" sort="Karasik, David" uniqKey="Karasik D" first="David" last="Karasik">David Karasik</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Davey Smith, George" sort="Davey Smith, George" uniqKey="Davey Smith G" first="George" last="Davey-Smith">George Davey-Smith</name><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V" last="Smith">Albert V. Smith</name><affiliation><nlm:aff id="A63">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Siggeirsdottir, Kristin" sort="Siggeirsdottir, Kristin" uniqKey="Siggeirsdottir K" first="Kristin" last="Siggeirsdottir">Kristin Siggeirsdottir</name><affiliation><nlm:aff id="A63">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B" last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="A88">Laboratory of Epidemiology, National Institute on Aging, National Institutes of Health, Bethesda, USA</nlm:aff></affiliation></author><author><name sortKey="Zillikens, M Carola" sort="Zillikens, M Carola" uniqKey="Zillikens M" first="M Carola" last="Zillikens">M Carola Zillikens</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Meurs, Joyce Bj" sort="Van Meurs, Joyce Bj" uniqKey="Van Meurs J" first="Joyce Bj" last="Van Meurs">Joyce Bj Van Meurs</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Thorsteinsdottir, Unnur" sort="Thorsteinsdottir, Unnur" uniqKey="Thorsteinsdottir U" first="Unnur" last="Thorsteinsdottir">Unnur Thorsteinsdottir</name><affiliation><nlm:aff id="A17">Department of Population Genomics, deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A64">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Maurano, Matthew T" sort="Maurano, Matthew T" uniqKey="Maurano M" first="Matthew T" last="Maurano">Matthew T. Maurano</name><affiliation><nlm:aff id="A89">Department of Genome Sciences, University of Washington, Seattle, USA</nlm:aff></affiliation></author><author><name sortKey="Timpson, Nicholas J" sort="Timpson, Nicholas J" uniqKey="Timpson N" first="Nicholas J" last="Timpson">Nicholas J. Timpson</name><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Soranzo, Nicole" sort="Soranzo, Nicole" uniqKey="Soranzo N" first="Nicole" last="Soranzo">Nicole Soranzo</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Durbin, Richard" sort="Durbin, Richard" uniqKey="Durbin R" first="Richard" last="Durbin">Richard Durbin</name><affiliation><nlm:aff id="A23">Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Wilson, Scott G" sort="Wilson, Scott G" uniqKey="Wilson S" first="Scott G" last="Wilson">Scott G. Wilson</name><affiliation><nlm:aff id="A32">Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</nlm:aff></affiliation><affiliation><nlm:aff id="A71">Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A90">School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia</nlm:aff></affiliation></author><author><name sortKey="Ntzani, Evangelia E" sort="Ntzani, Evangelia E" uniqKey="Ntzani E" first="Evangelia E" last="Ntzani">Evangelia E. Ntzani</name><affiliation><nlm:aff id="A91">Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece</nlm:aff></affiliation><affiliation><nlm:aff id="A92">Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, USA</nlm:aff></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><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A64">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A93">CEO, deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Hinds, David A" sort="Hinds, David A" uniqKey="Hinds D" first="David A" last="Hinds">David A. Hinds</name><affiliation><nlm:aff id="A16">Department of Research, 23andMe, Inc. Mountain View, USA</nlm:aff></affiliation></author><author><name sortKey="Spector, Tim" sort="Spector, Tim" uniqKey="Spector T" first="Tim" last="Spector">Tim Spector</name><affiliation><nlm:aff id="A32">Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Cupples, L Adrienne" sort="Cupples, L Adrienne" uniqKey="Cupples L" first="L Adrienne" last="Cupples">L Adrienne Cupples</name><affiliation><nlm:aff id="A18">Department of Biostatistics, Boston University School of Public Health, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A94">Framingham Heart Study, Framingham, USA</nlm:aff></affiliation></author><author><name sortKey="Ohlsson, Claes" sort="Ohlsson, Claes" uniqKey="Ohlsson C" first="Claes" last="Ohlsson">Claes Ohlsson</name><affiliation><nlm:aff id="A19">Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</nlm:aff></affiliation></author><author><name sortKey="Greenwood, Celia Mt" sort="Greenwood, Celia Mt" uniqKey="Greenwood C" first="Celia Mt" last="Greenwood">Celia Mt Greenwood</name><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Department of Human Genetics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A95">Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A96">Department of Oncology, McGill University, Montreal, Canada</nlm:aff></affiliation></author><author><name sortKey="Jackson, Rebecca D" sort="Jackson, Rebecca D" uniqKey="Jackson R" first="Rebecca D" last="Jackson">Rebecca D. Jackson</name><affiliation><nlm:aff id="A97">Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio USA</nlm:aff></affiliation></author><author><name sortKey="Rowe, David W" sort="Rowe, David W" uniqKey="Rowe D" first="David W" last="Rowe">David W. Rowe</name><affiliation><nlm:aff id="A85">Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA</nlm:aff></affiliation></author><author><name sortKey="Loomis, Cynthia A" sort="Loomis, Cynthia A" uniqKey="Loomis C" first="Cynthia A" last="Loomis">Cynthia A. Loomis</name><affiliation><nlm:aff id="A98">The Ronald O Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York USA</nlm:aff></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><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A14">MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Ackert Bicknell, Cheryl L" sort="Ackert Bicknell, Cheryl L" uniqKey="Ackert Bicknell C" first="Cheryl L" last="Ackert-Bicknell">Cheryl L. Ackert-Bicknell</name><affiliation><nlm:aff id="A35">The Jackson Laboratory, Bar Harbor, Maine, USA</nlm:aff></affiliation></author><author><name sortKey="Joyner, Alexandra L" sort="Joyner, Alexandra L" uniqKey="Joyner A" first="Alexandra L" last="Joyner">Alexandra L. Joyner</name><affiliation><nlm:aff id="A8">Department of Developmental Biology, Sloan-Kettering Institute, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Duncan, Emma L" sort="Duncan, Emma L" uniqKey="Duncan E" first="Emma L" last="Duncan">Emma L. Duncan</name><affiliation><nlm:aff id="A9">The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A99">Department of Diabetes and Endocrinology, Royal Brisbane and Women’s Hospital, Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Kiel, Douglas P" sort="Kiel, Douglas P" uniqKey="Kiel D" first="Douglas P" last="Kiel">Douglas P. Kiel</name><affiliation><nlm:aff id="A3">Institute for Aging Research, Hebrew SeniorLife, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Harvard Medical School, Boston, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A100">Beth Israel Deaconess Medical Center, Boston, USA</nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="A6">Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</nlm:aff></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><nlm:aff id="A1">Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</nlm:aff></affiliation></author></analytic><series><title level="j">Nature</title><idno type="ISSN">0028-0836</idno><idno type="eISSN">1476-4687</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>SUMMARY</title><p id="P2">The extent to which low-frequency (minor allele frequency [MAF] between 1–5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is largely unknown. Bone mineral density (BMD) is highly heritable, is a major predictor of osteoporotic fractures and has been previously associated with common genetic variants<sup><xref rid="R1" ref-type="bibr">1</xref>–<xref rid="R8" ref-type="bibr">8</xref></sup>, and rare, population-specific, coding variants<sup><xref rid="R9" ref-type="bibr">9</xref></sup>. Here we identify novel non-coding genetic variants with large effects on BMD (<italic>n<sub>total</sub></italic> = 53,236) and fracture (n<sub>total</sub> = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (<italic>n</italic>=2,882 from UK10K), whole-exome sequencing (<italic>n</italic>= 3,549), deep imputation of genotyped samples using a combined UK10K/1000Genomes reference panel (<italic>n</italic>=26,534), and <italic>de-novo</italic> replication genotyping (<italic>n</italic>= 20,271). We identified a low-frequency non-coding variant near a novel locus, <italic>EN1,</italic> with an effect size 4-fold larger than the mean of previously reported common variants for lumbar spine BMD<sup><xref rid="R8" ref-type="bibr">8</xref></sup> (rs11692564[T], MAF = 1.7%, replication effect size = +0.20 standard deviations [SD], <italic>Pmeta</italic> = 2×10<sup>−14</sup>), which was also associated with a decreased risk of fracture (OR = 0.85; P = 2×10<sup>−11</sup>; n<sub>cases</sub> = 98,742 and n<sub>controls</sub> = 409,511). Using an <italic>En1<sup>Cre/flox</sup></italic> mouse model, we observed that conditional loss of <italic>En1</italic> results in low bone mass, likely as a consequence of high bone turn-over. We also identified a novel low-frequency non-coding variant with large effects on BMD near <italic>WNT16</italic> (rs148771817[T], MAF = 1.1%, replication effect size = +0.39 SD, <italic>P<sub>meta</sub></italic> = 1×10<sup>−11</sup>). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0410462</journal-id><journal-id journal-id-type="pubmed-jr-id">6011</journal-id><journal-id journal-id-type="nlm-ta">Nature</journal-id><journal-id journal-id-type="iso-abbrev">Nature</journal-id><journal-title-group><journal-title>Nature</journal-title></journal-title-group><issn pub-type="ppub">0028-0836</issn><issn pub-type="epub">1476-4687</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26367794</article-id><article-id pub-id-type="pmc">4755714</article-id><article-id pub-id-type="doi">10.1038/nature14878</article-id><article-id pub-id-type="manuscript">CAMS5439</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Whole-genome sequencing identifies <italic>EN1</italic> as a determinant of bone density and fracture</article-title></title-group><contrib-group><contrib 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ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Brown</surname><given-names>Matthew A</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Stefansson</surname><given-names>Kari</given-names></name><xref ref-type="aff" rid="A64">64</xref><xref ref-type="aff" rid="A93">93</xref></contrib><contrib contrib-type="author"><name><surname>Hinds</surname><given-names>David A</given-names></name><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Spector</surname><given-names>Tim</given-names></name><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Cupples</surname><given-names>L Adrienne</given-names></name><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A94">94</xref></contrib><contrib contrib-type="author"><name><surname>Ohlsson</surname><given-names>Claes</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Greenwood</surname><given-names>Celia MT</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A33">33</xref><xref ref-type="aff" rid="A95">95</xref><xref ref-type="aff" rid="A96">96</xref></contrib><contrib contrib-type="author"><name><surname>Jackson</surname><given-names>Rebecca D</given-names></name><xref ref-type="aff" rid="A97">97</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Rowe</surname><given-names>David W</given-names></name><xref ref-type="aff" rid="A85">85</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Loomis</surname><given-names>Cynthia A</given-names></name><xref ref-type="aff" rid="A98">98</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Evans</surname><given-names>David M</given-names></name><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A14">14</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Ackert-Bicknell</surname><given-names>Cheryl L</given-names></name><xref ref-type="aff" rid="A35">35</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Joyner</surname><given-names>Alexandra L</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Duncan</surname><given-names>Emma L</given-names></name><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A99">99</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Kiel</surname><given-names>Douglas P</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A100">100</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Rivadeneira</surname><given-names>Fernando</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A28">28</xref><xref ref-type="aff" rid="A34">34</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><contrib contrib-type="author"><name><surname>Richards</surname><given-names>J Brent</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A32">32</xref><xref rid="FN3" ref-type="author-notes">†</xref></contrib><on-behalf-of>for the GEFOS and UK10K Consortia</on-behalf-of></contrib-group><aff id="A1"><label>1</label>Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal, Canada</aff><aff id="A2"><label>2</label>Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada</aff><aff id="A3"><label>3</label>Institute for Aging Research, Hebrew SeniorLife, Boston, USA</aff><aff id="A4"><label>4</label>Harvard Medical School, Boston, USA</aff><aff id="A5"><label>5</label>Broad Institute of MIT and Harvard, Boston, USA</aff><aff id="A6"><label>6</label>Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="A7"><label>7</label>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA</aff><aff id="A8"><label>8</label>Department of Developmental Biology, Sloan-Kettering Institute, New York, NY, USA</aff><aff id="A9"><label>9</label>The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia</aff><aff id="A10"><label>10</label>Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY</aff><aff id="A11"><label>11</label>Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, New York, USA</aff><aff id="A12"><label>12</label>Rheumatology Divison, Hospital for Special Surgery New York, New York, USA</aff><aff id="A13"><label>13</label>School of Clinical Science, University of Bristol, Bristol, United Kingdom</aff><aff id="A14"><label>14</label>MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom</aff><aff id="A15"><label>15</label>Fred Hutchinson Cancer Research Center, Seattle, USA</aff><aff id="A16"><label>16</label>Department of Research, 23andMe, Inc. Mountain View, USA</aff><aff id="A17"><label>17</label>Department of Population Genomics, deCODE Genetics, Reykjavik, Iceland</aff><aff id="A18"><label>18</label>Department of Biostatistics, Boston University School of Public Health, Boston, USA</aff><aff id="A19"><label>19</label>Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</aff><aff id="A20"><label>20</label>California Pacific Medical Center, San Francisco, USA</aff><aff id="A21"><label>21</label>Department of Public Health and Preventative Medicine, Oregon Health & Science University, Portland, USA</aff><aff id="A22"><label>22</label>Bone & Mineral Unit, Oregon Health & Science University, Portland, USA</aff><aff id="A23"><label>23</label>Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom</aff><aff id="A24"><label>24</label>Departments of Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden</aff><aff id="A25"><label>25</label>Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden</aff><aff id="A26"><label>26</label>Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden</aff><aff id="A27"><label>27</label>McGill University and Genome Quebec Innovation Centre, Montreal, Canada</aff><aff id="A28"><label>28</label>Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="A29"><label>29</label>Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, USA</aff><aff id="A30"><label>30</label>Department of Medical and Clinical Informatics, Oregon Health & Science University, Portland, USA</aff><aff id="A31"><label>31</label>Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom</aff><aff id="A32"><label>32</label>Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom</aff><aff id="A33"><label>33</label>Department of Human Genetics, McGill University, Montreal, Canada</aff><aff id="A34"><label>34</label>Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands</aff><aff id="A35"><label>35</label>The Jackson Laboratory, Bar Harbor, Maine, USA</aff><aff id="A36"><label>36</label>Department of Biochemistry, McGill University, Montreal, Canada</aff><aff id="A37"><label>37</label>Department of Computer Science, Trinity University, San Antonio, Texas, USA</aff><aff id="A38"><label>38</label>Musculoskeletal Research Unit, University of Bristol, Bristol, United Kingdom</aff><aff id="A39"><label>39</label>Medical Research Council Epidemiology Unit, University of Southhampton, Southhampton, United Kingdom</aff><aff id="A40"><label>40</label>Department of Radiation Sciences, Umeå University, Umeå, Sweden</aff><aff id="A41"><label>41</label>School of Public Health, University of Wisconsin, Milwaukee, USA</aff><aff id="A42"><label>42</label>School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom</aff><aff id="A43"><label>43</label>Department of Statistics, deCODE Genetics, Reykjavik, Iceland</aff><aff id="A44"><label>44</label>Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands</aff><aff id="A45"><label>45</label>Department of Human Nutrition, Wageningen University, Wageningen, The Netherlands</aff><aff id="A46"><label>46</label>Department of Internal Medicine, Section Geriatrics, Academic Medical Center, Amsterdam, The Netherlands</aff><aff id="A47"><label>47</label>Nordic Bioscience, Herlev, Denmark</aff><aff id="A48"><label>48</label>Cordeliers Research Centre, INSERM UMRS 1138, Paris, France</aff><aff id="A49"><label>49</label>Institute of Cardiometabolism and Nutrition, University Pierre & Marie Curie, Paris, France</aff><aff id="A50"><label>50</label>Departments of Medicine (Cardiovascular Medicine), Centre for Public Health Genomics, University of Virginia, Charlottesville, Virginia</aff><aff id="A51"><label>51</label>Department of Genetics, University of Barcelona, Barcelona, Spain</aff><aff id="A52"><label>52</label>U-720, Centre for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona, Spain</aff><aff id="A53"><label>53</label>Department of Human Molecular Genetics, The Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain</aff><aff id="A54"><label>54</label>Women’s Health Center of Excellence Family Medicine and Public Health, University of California - San Diego, San Diego, USA</aff><aff id="A55"><label>55</label>Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA</aff><aff id="A56"><label>56</label>Osteoporosis & Bone Biology Program, Garvan Institute of Medical Research, Sydney, Australia</aff><aff id="A57"><label>57</label>School of Medicine Sydney, University of Notre Dame Australia, Sydney, Australia</aff><aff id="A58"><label>58</label>St. Vincent’s Hospital & Clinical School, NSW University, Sydney, Australia</aff><aff id="A59"><label>59</label>Musculoskeletal Research Group, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain</aff><aff id="A60"><label>60</label>Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III, Spain</aff><aff id="A61"><label>61</label>Department of Internal Medicine, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain</aff><aff id="A62"><label>62</label>Neuroepidemiology Section, National Institute on Aging, National Institutes on Health, Bethesda, USA</aff><aff id="A63"><label>63</label>Icelandic Heart Association, Kopavogur, Iceland</aff><aff id="A64"><label>64</label>Faculty of Medicine, University of Iceland, Reykjavik, Iceland</aff><aff id="A65"><label>65</label>Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden</aff><aff id="A66"><label>66</label>Department of Orthopaedics, Skåne University Hospital Malmö, Sweden</aff><aff id="A67"><label>67</label>Department of Medical Sciences, University of Uppsala, Uppsala, Sweden</aff><aff id="A68"><label>68</label>Department of Surgical and Perioperative Sciences, Umeå Unviersity, Umeå, Sweden</aff><aff id="A69"><label>69</label>Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec City, Canada</aff><aff id="A70"><label>70</label>Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec City, Canada</aff><aff id="A71"><label>71</label>Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia</aff><aff id="A72"><label>72</label>Department of Medicine, University of Western Australia, Perth, Australia</aff><aff id="A73"><label>73</label>Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark</aff><aff id="A74"><label>74</label>Department of Endocrinology, Odense University Hospital, Odense C, Denmark</aff><aff id="A75"><label>75</label>Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark</aff><aff id="A76"><label>76</label>Clinical Gerontology Unit, Unviersity of Cambridge, Cambridge, UK</aff><aff id="A77"><label>77</label>Medicine and Public Health and Primary Care, University of Cambridge, Cambridge, UK</aff><aff id="A78"><label>78</label>Institute of Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, United Kingdom</aff><aff id="A79"><label>79</label>Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta</aff><aff id="A80"><label>80</label>Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden</aff><aff id="A81"><label>81</label>Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain</aff><aff id="A82"><label>82</label>Department of Internal Medicine, Hospital U.M. Valdecilla- IDIVAL, Santander, Spain</aff><aff id="A83"><label>83</label>Department of Legal Medicine, University of Cantabria, Santander, Spain</aff><aff id="A84"><label>84</label>Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK</aff><aff id="A85"><label>85</label>Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA</aff><aff id="A86"><label>86</label>Department of Medicine and Physiology, McGill University, Montreal, Canada</aff><aff id="A87"><label>87</label>Department of Medicine, Oregon Health & Science University, Portland, USA</aff><aff id="A88"><label>88</label>Laboratory of Epidemiology, National Institute on Aging, National Institutes of Health, Bethesda, USA</aff><aff id="A89"><label>89</label>Department of Genome Sciences, University of Washington, Seattle, USA</aff><aff id="A90"><label>90</label>School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia</aff><aff id="A91"><label>91</label>Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece</aff><aff id="A92"><label>92</label>Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, USA</aff><aff id="A93"><label>93</label>CEO, deCODE Genetics, Reykjavik, Iceland</aff><aff id="A94"><label>94</label>Framingham Heart Study, Framingham, USA</aff><aff id="A95"><label>95</label>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada</aff><aff id="A96"><label>96</label>Department of Oncology, McGill University, Montreal, Canada</aff><aff id="A97"><label>97</label>Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio USA</aff><aff id="A98"><label>98</label>The Ronald O Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York USA</aff><aff id="A99"><label>99</label>Department of Diabetes and Endocrinology, Royal Brisbane and Women’s Hospital, Brisbane, Australia</aff><aff id="A100"><label>100</label>Beth Israel Deaconess Medical Center, Boston, USA</aff><author-notes><corresp id="FN1">Correspondence to: Brent Richards, Pavillon H-413, Jewish General Hospital, 3755 Cote Ste Catherine, Montreal, QC, Canada, H3T 1E2, <email>brent.richards@mcgill.ca</email></corresp><fn id="FN2"><label>*</label><p>Denotes shared contribution</p></fn><fn id="FN3"><label>†</label><p>Denotes shared contribution</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>10</day><month>2</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>14</day><month>9</month><year>2015</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>10</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>4</month><year>2016</year></pub-date><volume>526</volume><issue>7571</issue><fpage>112</fpage><lpage>117</lpage><pmc-comment>elocation-id from pubmed: 10.1038/nature14878</pmc-comment>
<abstract><title>SUMMARY</title><p id="P2">The extent to which low-frequency (minor allele frequency [MAF] between 1–5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is largely unknown. Bone mineral density (BMD) is highly heritable, is a major predictor of osteoporotic fractures and has been previously associated with common genetic variants<sup><xref rid="R1" ref-type="bibr">1</xref>–<xref rid="R8" ref-type="bibr">8</xref></sup>, and rare, population-specific, coding variants<sup><xref rid="R9" ref-type="bibr">9</xref></sup>. Here we identify novel non-coding genetic variants with large effects on BMD (<italic>n<sub>total</sub></italic> = 53,236) and fracture (n<sub>total</sub> = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (<italic>n</italic>=2,882 from UK10K), whole-exome sequencing (<italic>n</italic>= 3,549), deep imputation of genotyped samples using a combined UK10K/1000Genomes reference panel (<italic>n</italic>=26,534), and <italic>de-novo</italic> replication genotyping (<italic>n</italic>= 20,271). We identified a low-frequency non-coding variant near a novel locus, <italic>EN1,</italic> with an effect size 4-fold larger than the mean of previously reported common variants for lumbar spine BMD<sup><xref rid="R8" ref-type="bibr">8</xref></sup> (rs11692564[T], MAF = 1.7%, replication effect size = +0.20 standard deviations [SD], <italic>Pmeta</italic> = 2×10<sup>−14</sup>), which was also associated with a decreased risk of fracture (OR = 0.85; P = 2×10<sup>−11</sup>; n<sub>cases</sub> = 98,742 and n<sub>controls</sub> = 409,511). Using an <italic>En1<sup>Cre/flox</sup></italic> mouse model, we observed that conditional loss of <italic>En1</italic> results in low bone mass, likely as a consequence of high bone turn-over. We also identified a novel low-frequency non-coding variant with large effects on BMD near <italic>WNT16</italic> (rs148771817[T], MAF = 1.1%, replication effect size = +0.39 SD, <italic>P<sub>meta</sub></italic> = 1×10<sup>−11</sup>). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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