Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for l...

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Published inNature genetics Vol. 44; no. 5; pp. 491 - 501
Main Authors Estrada, Karol, Styrkarsdottir, Unnur, Evangelou, Evangelos, Hsu, Yi-Hsiang, Ntzani, Evangelia E, Albagha, Omar M E, Koller, Daniel L, Minster, Ryan L, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Zheng, Hou-Feng, Alonso, Nerea, Kammerer, Candace M, Kaptoge, Stephen K, Leo, Paul J, Wilson, James F, Alen, Markku, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Duggan, David J, Garcia, Melissa, Husted, Lise Bjerre, Jameson, Karen A, Kim, Ghi Su, Kooperberg, Charles, Kruk, Marcin, Laaksonen, Marika, Leung, Ping C, Lewis, Joshua R, Nogues, Xavier, Prezelj, Janez, Scollen, Serena, Svensson, Olle, Trompet, Stella, Woo, Jean, Zhu, Kun, Cheng, Sulin, Dedoussis, George, Frost, Morten, Goltzman, David, Kähönen, Mika, Karlsson, Magnus, Langdahl, Bente Lomholt, Lips, Paul, Lorenc, Roman S, Mellström, Dan, Olmos, José M, Pettersson-Kymmer, Ulrika, Riancho, José A, Ridker, Paul M, Rousseau, François, lagboom, P Eline S, Urreizti, Roser, Zarrabeitia, María T, Castano-Betancourt, Martha, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gómez, Carolina, Th Palsson, Stefan, Rotter, Jerome I, Sigurdsson, Gunnar, van Meurs, Joyce B J, Williams, Frances M K, Zhou, Yanhua, Pastinen, Tomi, Cauley, Jane A, Chasman, Daniel I, Clark, Graeme R, Cummings, Steven R, Eastell, Richard, Eisman, John A, Hofman, Albert, Jukema, J Wouter, Khaw, Kay-Tee, Lehtimäki, Terho, Liu, Yongmei, Oostra, Ben A, Pols, Huibert A P, Reid, Ian R, Robbins, John, Sambrook, Philip N, Sham, Pak Chung, Shuldiner, Alan R, van Duijn, Cornelia M, Wareham, Nick J, Econs, Michael J, Harris, Tamara B, Kung, Annie Wai Chee, Streeten, Elizabeth A, Thorsteinsdottir, Unnur, Karasik, David, Richards, J Brent, Brown, Matthew A, Ralston, Stuart H, Ioannidis, John P A, Kiel, Douglas P
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.05.2012
Nature Publishing Group
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Online AccessGet full text
ISSN1061-4036
1546-1718
1546-1718
DOI10.1038/ng.2249

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Abstract Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture. Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance ( P < 5 × 10 −8 ). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk ( P < 5 × 10 −4 , Bonferroni corrected), of which six reached P < 5 × 10 −8 , including at 18p11.21 ( FAM210A ), 7q21.3 ( SLC25A13 ), 11q13.2 ( LRP5) , 4q22.1 ( MEPE ), 2p16.2 ( SPTBN1 ) and 10q21.1 ( DKK1 ). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
AbstractList Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10^sup -8^). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10^sup -4^, Bonferroni corrected), of which six reached P < 5 × 10^sup -8^, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. [PUBLICATION ABSTRACT]
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P &lt; 5 x 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P &lt; 5 x 10(-4), Bonferroni corrected), of which six reached P &lt; 5 x 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 x 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 x 10(-4), Bonferroni corrected), of which six reached P < 5 x 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Bone mineral density (BMD) is the most important predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and East Asian ancestry. We tested the top-associated BMD markers for replication in 50,933 independent subjects and for risk of low-trauma fracture in 31,016 cases and 102,444 controls. We identified 56 loci (32 novel)associated with BMD atgenome-wide significant level (P<5×10 −8 ). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal-stem-cell differentiation, endochondral ossification and the Wnt signalling pathways. However, we also discovered loci containing genes not known to play a role in bone biology. Fourteen BMD loci were also associated with fracture risk (P<5×10 −4 , Bonferroni corrected), of which six reached P<5×10 −8 including: 18p11.21 ( C18orf19 ), 7q21.3 ( SLC25A13 ), 11q13.2 ( LRP5) , 4q22.1 ( MEPE ), 2p16.2 ( SPTBN1 ) and 10q21.1 ( DKK1 ). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture. Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance ( P < 5 × 10 −8 ). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk ( P < 5 × 10 −4 , Bonferroni corrected), of which six reached P < 5 × 10 −8 , including at 18p11.21 ( FAM210A ), 7q21.3 ( SLC25A13 ), 11q13.2 ( LRP5) , 4q22.1 ( MEPE ), 2p16.2 ( SPTBN1 ) and 10q21.1 ( DKK1 ). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 x 10 super(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 x 10 super(-4), Bonferroni corrected), of which six reached P < 5 x 10 super(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P &lt; 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P &lt; 5 × 10(-4), Bonferroni corrected), of which six reached P &lt; 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 x [10.sup.-8]). Several of these factors cluster within the RANKRANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 x [10.sup.-4], Bonferroni corrected), of which six reached P < 5 x [10.sup.-8], including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11 q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Audience Academic
Author Albagha, Omar M E
Koromila, Theodora
Eastell, Richard
Jackson, Rebecca D
Cupples, L Adrienne
Spector, Timothy D
Van Hul, Wim
Herrera, Lizbeth
Urreizti, Roser
Pastinen, Tomi
Gudnason, Vilmundur
Streeten, Elizabeth A
Frost, Morten
Rotter, Jerome I
Minster, Ryan L
Harris, Tamara B
Amin, Najaf
Khaw, Kay-Tee
Richards, J Brent
Tang, Nelson L S
Liu, Yongmei
Pols, Huibert A P
Oei, Ling
Garcia, Melissa
Econs, Michael J
Kemp, John P
Ljunggren, Östen
Reid, Ian R
Stefansson, Kari
Jones, Graeme
McCloskey, Eugene
Khusnutdinova, Elza
Hsu, Yi-Hsiang
Masi, Laura
Siggeirsdottir, Kristin
Eisman, John A
Nguyen, Tuan V
Williams, Frances M K
Sigurdsson, Gunnar
Wilson, James F
Lewis, Joshua R
Sham, Pak Chung
Aragaki, Aaron K
Uitterlinden, André G
Estrada, Karol
Liu, Ching-Ti
Karlsson, Magnus
Zarrabeitia, María T
Kähönen, Mika
Wareham, Nick J
Reid, David M
Khusainova, Rita
Lee, Seung Hun
Jukema, J Wouter
Lorenc, Roman S
Nogues, Xavier
Xiao, Su-Mei
Christiansen, Claus
Langdahl, Bente Lomholt
Mellström, Dan
Duggan, David J
Peacock, Munro
Psaty, Bruce M
Koh, Jung-Min
Viikari
AuthorAffiliation 67 Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
7 Department of Medicine, Harvard Medical School, Boston, USA
35 Department of Medicine, University of New South Wales, Sydney, Australia
41 Unité de recherche en génétique humaine et moléculaire, Centre de recherche du Centre hospitalier universitaire de Québec - Hôpital St-François-d’Assise (CHUQ/HSFA), Québec City, Canada
64 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
97 Wellcome Trust Sanger Institute, Hinxton, UK
81 Department of Endocrinology, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands
101 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
118 Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
58 Department of Medicine, University of Cambridge, Cambridge, UK
100 Department of Epidemiology and Biostatistics, Lady Davis Institute, McGill University, Montreal, Canada
93 Depart
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– name: 115 Menzies Research Institute, University of Tasmania, Hobart, Australia
– name: 26 Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
– name: 81 Department of Endocrinology, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands
– name: 87 The APOGEE-Net/CanGèneTest Network on Genetic Health Services and Policy, Université Laval, Québec City, Canada
– name: 137 Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, McGill University, Montreal, Canada
– name: 114 Center for Clinical and Translational Science, The Ohio State University, Columbus, USA
– name: 19 Australian Centre for Ecogenomics, University of Queensland, Brisbane, Australia
– name: 40 Department of Internal Medicine, Hospital del Mar, Instituto Municipal de Investigación Médica (IMIM), Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF), Universitat Autònoma de Barcelona (UAB), Barcelone, Spain
– name: 93 Department of Medicine, University of Turku, Turku, Finland
– name: 58 Department of Medicine, University of Cambridge, Cambridge, UK
– name: 35 Department of Medicine, University of New South Wales, Sydney, Australia
– name: 97 Wellcome Trust Sanger Institute, Hinxton, UK
– name: 17 Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK
– name: 71 Robertson Center for Biostatistics, University of Glasgow, Glasgow, United Kingdom
– name: 8 Human Genetics Group, University of Queensland Diamantina Institute, Brisbane, Australia
– name: 67 Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
– name: 60 Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
– name: 116 Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands
– name: 5 Department of Hygiene and Epidemiology, University of Ioannina, Ioannina, Greece
– name: 64 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
– name: 91 Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
– name: 3 Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands
– name: 38 Translational Genomics Research Institute, Phoenix, USA
– name: 46 Ufa Scientific Centre of Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa, Russia
– name: 92 Department of Medicine, Turku University Hospital, Turku, Finland
– name: 111 California Pacific Medical Center, San Francisco, CA, USA
– name: 12 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA
– name: 78 Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland
– name: 22 Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA
– name: 33 Faculty of Medicine, University of Iceland, Reykjavik, Iceland
– name: 104 Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, England
– name: 14 Department of Biostatistics, Boston University School of Public Health, Boston, USA
– name: 117 Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
– name: 105 Department of Clinical Biochemistry, Lovisenberg Deacon Hospital, Oslo, Norway
– name: 1 Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
– name: 133 Framingham Heart Study, Framingham, USA
– name: 76 Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla and Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain
– name: 13 Cardiovascular Health Research Unit, University of Washington, Seattle, USA
– name: 41 Unité de recherche en génétique humaine et moléculaire, Centre de recherche du Centre hospitalier universitaire de Québec - Hôpital St-François-d’Assise (CHUQ/HSFA), Québec City, Canada
– name: 32 Icelandic Heart Association, Kopavogur, Iceland
– name: 106 Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
– name: 37 Department of Orthopaedic Surgery, Medical School University of Thessalia, Larissa, Greece
– name: 21 Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong, China
– name: 119 Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland
– name: 6 Institute for Aging Research, Hebrew SeniorLife, Boston, USA
– name: 118 Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
– name: 88 Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
– name: 49 Department of Genetics and Biotechnology, Faculty of Biology, University of Athens, Athens, Greece
– name: 70 Department of Nutrition and Dietetics, Harokopio University, Athens, Greece
– name: 20 Department of Medicine, The University of Hong Kong, Hong Kong, China
– name: 130 Geriatric Research and Education Clinical Center (GRECC), Veterans Administration Medical Center, Baltimore, MD, USA
– name: 101 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
– name: 77 Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
– name: 69 Center for Clinical and Basic Research (CCBR)-Synarc, Ballerup, Denmark
– name: 39 Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA
– name: 95 Department of Human Genetics, McGill University, Montreal, Canada
– name: 103 Department of Endocrinology and Metabolism, University Hospital, Reykjavik, Iceland
– name: 66 Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland
– name: 74 Department of Medicine, McGill University, Montreal, Canada
– name: 79 Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Department of Orthopaedics, Lund University, Malmö, Sweden
– name: 89 Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
– name: 131 Department of Preventive Medicine, University of Tennessee College of Medicine, Memphis, TN, USA
– name: 53 Department of Internal Medicine, University of Florence, Florence, Italy
– name: 42 Department of Public Health and Clinical Medicine, Umeå Unviersity, Umeå, Sweden
– name: 98 Department of Orthopedic Surgery, Akureyri Hospital, Akureyri, Iceland
– name: 108 Division of Genetics and Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States
– name: 126 Department of Medicine, University of Davis, Sacramento, CA, USA
– name: 11 Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK
– name: 57 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA
– name: 80 Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
– name: 54 Department of Clinical Biochemistry, University of Ljubljana, Ljubljana, Slovenia
– name: 61 Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
– name: 82 Extramuraal Geneeskundig Onderzoek (EMGO) Institute for Health and Care Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands
– name: 112 National Institute for Health and Research (NIHR) Musculoskeletal Biomedical Research Unit, University of Sheffield, Sheffield, UK
– name: 84 Department of Pharmacology and Neuroscience, Umeå University, Umeå, Sweden
– name: 99 Institution of Health Science, University Of Akureyri, Akureyri, Iceland
– name: 86 Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec City, Canada
– name: 110 Department of Epidemiology, University of Pittsburgh, Pittsburgh, USA
– name: 113 Department of Internal Medicine, The Ohio State University, Columbus, USA
– name: 90 Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
– name: 59 Department of Surgical and Perioperative Sciences, Umeå Unviersity, Umeå, Sweden
– name: 129 Centre for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong, China
– name: 134 Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, USA
– name: 47 Biological Department, Bashkir State University, Ufa, Russia
– name: 100 Department of Epidemiology and Biostatistics, Lady Davis Institute, McGill University, Montreal, Canada
– name: 136 Medicine box 157, University of Cambridge, Cambridge, UK
– name: 10 Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
– name: 63 Department of Epidemiology and Biostatistics, Extramuraal Geneeskundig Onderzoek (EMGO) Institute for Health and Care Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands
– name: 132 MRC Epidemiology Unit Box 285, Medical Research Council, Cambridge, UK
– name: 15 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
– name: 50 Department of Biochemistry and Experimental Medicine, The Children’s Memorial Health Institute, Warsaw, Poland
– name: 96 McGill University and Genome Québec Innovation Centre, Montreal, Canada
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– name: 120 Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
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  organization: Department of Public Health and Primary Care, University of Cambridge, Department of Twin Research and Genetic Epidemiology, King's College London
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– sequence: 20
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  organization: Department of Human Genetics, Lady Davis Institute, McGill University
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  organization: Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh
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  givenname: Candace M
  surname: Kammerer
  fullname: Kammerer, Candace M
  organization: Department of Human Genetics, University of Pittsburgh
– sequence: 24
  givenname: Stephen K
  surname: Kaptoge
  fullname: Kaptoge, Stephen K
  organization: Department of Public Health and Primary Care, University of Cambridge
– sequence: 25
  givenname: Paul J
  surname: Leo
  fullname: Leo, Paul J
  organization: Human Genetics Group, University of Queensland Diamantina Institute
– sequence: 28
  givenname: James F
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  organization: Centre for Population Health Sciences, University of Edinburgh, MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh
– sequence: 30
  givenname: Markku
  surname: Alen
  fullname: Alen, Markku
  organization: Department of Medical Rehabilitation, Oulu University Hospital and Institute of Health Sciences
– sequence: 32
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  surname: Aspelund
  fullname: Aspelund, Thor
  organization: Icelandic Heart Association, Faculty of Medicine, University of Iceland
– sequence: 33
  givenname: Jacqueline R
  surname: Center
  fullname: Center, Jacqueline R
  organization: Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, Department of Medicine, University of New South Wales, Department of Endocrinology, St. Vincent's Hospital
– sequence: 34
  givenname: Zoe
  surname: Dailiana
  fullname: Dailiana, Zoe
  organization: Department of Orthopaedic Surgery, Medical School University of Thessalia
– sequence: 35
  givenname: David J
  surname: Duggan
  fullname: Duggan, David J
  organization: Translational Genomics Research Institute
– sequence: 36
  givenname: Melissa
  surname: Garcia
  fullname: Garcia, Melissa
  organization: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging
– sequence: 41
  givenname: Lise Bjerre
  surname: Husted
  fullname: Husted, Lise Bjerre
  organization: Department of Endocrinology and Internal Medicine, Aarhus University Hospital
– sequence: 42
  givenname: Karen A
  surname: Jameson
  fullname: Jameson, Karen A
  organization: MRC Lifecourse Epidemiology Unit, University of Southampton
– sequence: 44
  givenname: Ghi Su
  surname: Kim
  fullname: Kim, Ghi Su
  organization: Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine
– sequence: 45
  givenname: Charles
  surname: Kooperberg
  fullname: Kooperberg, Charles
  organization: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center
– sequence: 47
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  surname: Kruk
  fullname: Kruk, Marcin
  organization: Department of Biochemistry and Experimental Medicine, The Children's Memorial Health Institute
– sequence: 48
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  surname: Laaksonen
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  organization: Department of Food and Environmental Sciences, University of Helsinki
– sequence: 51
  givenname: Ping C
  surname: Leung
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  organization: Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong
– sequence: 52
  givenname: Joshua R
  surname: Lewis
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  organization: School of Medicine and Pharmacology, University of Western Australia, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital
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  organization: Department of Endocrinology, University Medical Center
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  organization: Department of Medicine, University of Cambridge
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  organization: Department of Surgical and Perioperative Sciences, Umeå Unviersity
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  organization: Department of Cardiology, Leiden University Medical Center, Department of Gerontology and Geriatrics, Leiden University Medical Center
– sequence: 67
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  surname: Woo
  fullname: Woo, Jean
  organization: Department of Medicine and Therapeutics, The Chinese University of Hong Kong
– sequence: 68
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  surname: Zhu
  fullname: Zhu, Kun
  organization: School of Medicine and Pharmacology, University of Western Australia, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital
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  givenname: Sulin
  surname: Cheng
  fullname: Cheng, Sulin
  organization: Department of Health Sciences, University of Jyväskylä, Department of Orthopaedics and Traumatology, Kuopio University Hospital
– sequence: 75
  givenname: George
  surname: Dedoussis
  fullname: Dedoussis, George
  organization: Department of Nutrition and Dietetics, Harokopio University
– sequence: 77
  givenname: Morten
  surname: Frost
  fullname: Frost, Morten
  organization: Department of Endocrinology, Odense University Hospital, Clinical Institute, University of Southern Denmark
– sequence: 78
  givenname: David
  surname: Goltzman
  fullname: Goltzman, David
  organization: Department of Medicine, McGill University
– sequence: 80
  givenname: Mika
  surname: Kähönen
  fullname: Kähönen, Mika
  organization: Department of Clinical Physiology, Tampere University Hospital, Department of Clinical Physiology, University of Tampere School of Medicine
– sequence: 81
  givenname: Magnus
  surname: Karlsson
  fullname: Karlsson, Magnus
  organization: Department of Clinical Sciences, Clinical and Molecular Osteoporosis Research Unit, Lund University, Department of Orthopaedics, Lund University
– sequence: 85
  givenname: Bente Lomholt
  surname: Langdahl
  fullname: Langdahl, Bente Lomholt
  organization: Department of Endocrinology and Internal Medicine, Aarhus University Hospital
– sequence: 87
  givenname: Paul
  surname: Lips
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  organization: Department of Endocrinology, VU University Medical Center, Extramuraal Geneeskundig Onderzoek (EMGO) Institute for Health and Care Research, VU University Medical Center
– sequence: 89
  givenname: Roman S
  surname: Lorenc
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  organization: Department of Biochemistry and Experimental Medicine, The Children's Memorial Health Institute
– sequence: 91
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  organization: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
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  givenname: José M
  surname: Olmos
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  organization: Department of Medicine, University of Cantabria, Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla and Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV)
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  organization: Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School
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  surname: Rousseau
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  organization: Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Department of Molecular Epidemiology, Leiden University Medical Center
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  givenname: Roser
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  organization: Department of Genetics, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institut de Biomedicina de la Universitat de Barcelona (IBUB)
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  givenname: María T
  surname: Zarrabeitia
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  organization: Department of Internal Medicine, Erasmus Medical Center, Department of Epidemiology, Erasmus Medical Center, Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA)
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  organization: Department of Human Genetics, McGill University, McGill University and Genome Québec Innovation Centre
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  surname: Th Palsson
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  organization: deCODE Genetics
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  surname: Rotter
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  organization: Medical Genetics Institute, Cedars-Sinai Medical Center
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  organization: Faculty of Medicine, University of Iceland, Department of Endocrinology and Metabolism, University Hospital
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  organization: Department of Internal Medicine, Erasmus Medical Center, Department of Epidemiology, Erasmus Medical Center, Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA)
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  givenname: Frances M K
  surname: Williams
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  organization: Department of Twin Research and Genetic Epidemiology, King's College London
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  surname: Zhou
  fullname: Zhou, Yanhua
  organization: Department of Biostatistics, Boston University School of Public Health
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  organization: Department of Human Genetics, McGill University, McGill University and Genome Québec Innovation Centre, Department of Medical Genetics, McGill University Health Centre
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  givenname: Jane A
  surname: Cauley
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  organization: Department of Epidemiology, University of Pittsburgh
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  surname: Chasman
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  organization: Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School
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  givenname: Graeme R
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  organization: Human Genetics Group, University of Queensland Diamantina Institute
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  organization: California Pacific Medical Center
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  organization: National Institute for Health and Research (NIHR), Musculoskeletal Biomedical Research Unit, University of Sheffield
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  organization: Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, Department of Medicine, University of New South Wales, Department of Endocrinology, St. Vincent's Hospital
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  organization: Department of Epidemiology, Erasmus Medical Center, Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA)
– sequence: 139
  givenname: J Wouter
  surname: Jukema
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  organization: Department of Cardiology, Leiden University Medical Center, Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute of the Netherlands
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  givenname: Kay-Tee
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  organization: Department of Public Health and Primary Care, University of Cambridge
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  givenname: Terho
  surname: Lehtimäki
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  organization: Department of Clinical Chemistry, Tampere University Hospital, Department of Clinical Chemistry, University of Tampere School of Medicine, Fimlab
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  surname: Liu
  fullname: Liu, Yongmei
  organization: Center for Human Genomics, Wake Forest University School of Medicine
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  fullname: Oostra, Ben A
  organization: Department of Clinical Genetics, Erasmus Medical Center
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  givenname: Huibert A P
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  organization: Department of Internal Medicine, Erasmus Medical Center, Department of Epidemiology, Erasmus Medical Center
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  organization: Department of Medicine, University of Auckland
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  organization: Department of Medicine, University of California, Davis, Sacramento, California, USA
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  surname: Sambrook
  fullname: Sambrook, Philip N
  organization: Kolling Institute, Royal North Shore Hospital, University of Sydney
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  fullname: Sham, Pak Chung
  organization: Department of Psychiatry, The University of Hong Kong, Centre for Reproduction, Development and Growth, The University of Hong Kong
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  givenname: Alan R
  surname: Shuldiner
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  organization: Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Geriatric Research and Education Clinical Center (GRECC), Veterans Administration Medical Center
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  givenname: Cornelia M
  surname: van Duijn
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  organization: Department of Epidemiology, Erasmus Medical Center
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  organization: MRC Epidemiology Unit Box 285, MRC
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  organization: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Department of Medicine, Indiana University School of Medicine
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  organization: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging
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  fullname: Kung, Annie Wai Chee
  organization: Department of Medicine, The University of Hong Kong, Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong
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  organization: Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Geriatric Research and Education Clinical Center (GRECC), Veterans Administration Medical Center
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  organization: deCODE Genetics, Faculty of Medicine, University of Iceland
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  organization: Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Harvard Medical School
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  organization: Department of Twin Research and Genetic Epidemiology, King's College London, Department of Human Genetics, Lady Davis Institute, McGill University, Department of Epidemiology and Biostatistics, Lady Davis Institute, McGill University, Department of Medicine, Lady Davis Institute, McGill University
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  organization: Human Genetics Group, University of Queensland Diamantina Institute
– sequence: 178
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  organization: Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh
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  surname: Ioannidis
  fullname: Ioannidis, John P A
  organization: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Stanford Prevention Research Center, Stanford University
– sequence: 180
  givenname: Douglas P
  surname: Kiel
  fullname: Kiel, Douglas P
  organization: Institute for Aging Research, Hebrew SeniorLife, Department of Medicine, Harvard Medical School
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CODEN NGENEC
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Issue 5
Keywords Osteoarticular system
Diseases of the osteoarticular system
Risk
Fracture
Identification
Bone
Locus
Trauma
Density
Metaanalysis
Language English
License http://www.springer.com/tdm
CC BY 4.0
Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
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These authors jointly directed this work.
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  year: 2010
  ident: BFng2249_CR31
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0013217
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  publication-title: Ann. Hum. Genet.
  doi: 10.1111/j.1469-1809.2008.00447.x
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  year: 2011
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  publication-title: Eur. J. Hum. Genet.
  doi: 10.1038/ejhg.2011.39
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Snippet Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with...
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck...
Bone mineral density (BMD) is the most important predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck...
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pubmed
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SubjectTerms 631/208/205/2138
631/208/2489/144
631/208/480
Agriculture
Animal Genetics and Genomics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Bone
Bone densitometry
Bone Density
Bone Density - genetics
Bone mineral density
Bones
Cancer Research
Cell differentiation
Clinical Medicine
Computational Biology
Densitometria òssia
Density
Endocrinology and Diabetes
Endokrinologi och diabetes
European Continental Ancestry Group
Extracellular Matrix Proteins
Extracellular Matrix Proteins - genetics
Female
Femur
Femur Neck
Femur Neck - physiopathology
Fractures
Fractures, Bone - genetics
Fundamental and applied biological sciences. Psychology
Fèmur
Gene Expression Profiling
Gene Function
Gene loci
Genes
Genetic aspects
Genetic Predisposition to Disease
Genetics
Genetics of eukaryotes. Biological and molecular evolution
genetik
Genome-Wide Association Study
Genomics
Genotype
Gens
Glycoproteins
Glycoproteins - genetics
Human Genetics
Humans
Identification and classification
Intercellular Signaling Peptides and Proteins
Intercellular Signaling Peptides and Proteins - genetics
Klinisk medicin
Low Density Lipoprotein Receptor-Related Protein-5
Low Density Lipoprotein Receptor-Related Protein-5 - genetics
Lumbar Vertebrae
Lumbar Vertebrae - physiopathology
Male
Medical and Health Sciences
Medical research
Medicin och hälsovetenskap
Mitochondrial Membrane Transport Proteins
Mitochondrial Membrane Transport Proteins - genetics
Orthopaedics
Ortopedi
Osteoporosis
Osteoporosis - genetics
Phosphoproteins
Phosphoproteins - genetics
physiopathology
Polymorphism
Polymorphism, Single Nucleotide - genetics
Quantitative Trait Loci
Risk Factors
Single Nucleotide
Spectrin
Spectrin - genetics
Spine
Stem cells
Vèrtebres lumbars
White People
Title Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
URI https://link.springer.com/article/10.1038/ng.2249
https://www.ncbi.nlm.nih.gov/pubmed/22504420
https://www.proquest.com/docview/1021186132
https://www.proquest.com/docview/1010233087
https://www.proquest.com/docview/1034809203
https://recercat.cat/handle/2072/336913
https://pubmed.ncbi.nlm.nih.gov/PMC3338864
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-54103
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-176250
https://gup.ub.gu.se/publication/161420
Volume 44
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