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

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Acknowledgements

We thank all study participants for making this work possible. This research and the Genetic Factors for Osteoporosis (GEFOS) consortium have been funded by the European Commission (HEALTH-F2-2008-201865-GEFOS). We acknowledge funding from the following organizations: the US National Institutes of Health (NIH; R01 AG18728, R01 HL088119, R01AR046838, U01 HL084756, P30 DK072488, T32 AG000262, F32 AR059469, P01 AG-18397, R01 AG041517, M01 RR-00750 and N01-AG-12100), the NIA Intramural Research Program (AG-023629, AG-15928, AG-20098 and AG-027058), Hjartavernd (the Icelandic Heart Association), the Althingi (the Icelandic Parliament), the Australian National Health and Medical Research Council (511132), the Australian Cancer Research Foundation and the Rebecca Cooper Foundation, the Australian National Health and Medical Research Council Career Development Award (569807 to E.L.D.), an MRC New Investigator Award (MRC G0800582 to D.M.E.), the Health Research Council of New Zealand, Sanofi-Aventis, Eli Lilly, Pfizer, Proctor & Gamble Pharmaceuticals, Roche, the Medical Benefits Fund (MBF) Living Well Foundation, the Ernst Heine Family Foundation, Arthritis Research UK (17539 and 15389), The Victorian Health Promotion Foundation, Geelong Region Medical Research Foundation, Australia (628582), Action Research UK, the European Commission (QLRT-2001-02629), the UK Food Standards Agency, BioPersMed (COMET K-project 825329), the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT), the Austrian Federal Ministry of Economics and Labour (BMWA), the Austrian Federal Ministry of Economy, Family and Youth (BMWFJ), the Styrian Business Promotion Agency (SFG), the Red de Envejecimiento y Fragilidad (RETICEF), Instituto Carlos III, the Spanish Ministry of Education and Science (SAF2010-15707), the Government of Catalonia (2009SGR971 and 2009SGR818), Instituto de Salud Carlos III–Fondo de Investigaciones Sanitarias (PI 06/0034 and PI08/0183), Healthway Health Promotion Foundation of Western Australia, Australasian Menopause Society and the Australian National Health and MRC Project (254627, 303169 and 572604), the Finnish Ministry of Education, Merck Frosst Canada, Eli Lilly Canada, Novartis Pharmaceuticals, Procter & Gamble Pharmaceuticals Canada, Servier Canada, Amgen Canada, The Dairy Farmers of Canada, The Arthritis Society, the US National Heart, Lung, and Blood Institute (NHLBI; N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL087652, HL105756 NINDS, HL 043851 and HL69757, CA 047988, and the Framingham Heart Study (N01-HC-25195) and its contract with Affymetrix, Inc, for genotyping services (N02-HL-6-4278)). Untied Educational Grants were provided by Amgen, Eli Lilly International, GE-Lunar, Merck Australia, Sanofi-Aventis Australia and Servier. Additional support was provided by the US National Center for Research Resources (M01-RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping Core), the US National Institute of Diabetes and Digestive and Kidney Diseases (DK063491 to the Southern California Diabetes Endocrinology Research Center), deCODE Genetics, The UK National Institute for Medical Research (NIMR) Biomedical Research Centre, the Cancer Research Campaign, the Stroke Association, the British Heart Foundation, the UK Department of Health, the Europe Against Cancer Programme Commission of the European Union, the Ministry of Agriculture, Fisheries and Food, EU Biomed 1 (BMHICT920182, CIPDCT925012, ERBC1PDCT 940229 and ERBC1PDCT930105), the UK MRC (G9321536 and G9800062), the Wellcome Trust Collaborative Research Initiative 1995, MAFF AN0523, EU Framework Programme 5 (FP5; QLK6-CT-2002-02629), the Food Standards Agency (N05046), the Netherlands Organization for Scientific Research (NWO), Erasmus University Medical Center, the Centre for Medical Systems Biology (CMSB1 and CMSB2) of the Netherlands Genomics Initiative (NGI), the F.I.R.M.O. Fondazione Raffaella Becagli, the National Institute for Arthritis, Musculoskeletal and Skin Diseases, the National Institute on Aging (R01 AR/AG 41398, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098 and R01 AR 050066), the Canadian Institutes for Health Research (86748), Federal Program of the Ministry of Education and Science of the Russian Federation Scientific and Pedagogical Staff of Innovative Russia in 2009–2013 (P-601), the Federal Program Research and Development of Prior Directions of Scientific-Technological Complex of Russia in 2007–2012 (16.512.11.2032), the Swedish Research Council (K2010-54X-09894-19-3, 2006-3832, K2010-52X-20229-05-3 and K20006-72X-20155013) the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg, the Lundberg Foundation, the Torsten and Ragnar Söderberg's Foundation, the Västra Götaland Foundation, the Göteborg Medical Society, the Novo Nordisk foundation, University of Athens, Greece (Kapodistrias 2009), the UK NIHR Musculoskeletal BRU Oxford, the UK NIHR Nutrition BRU Southampton, The Center for Inherited Disease Research (CIDR), National Institutes of Health (HHSN268200782096C), the Hong Kong Research Grant Council (HKU 768610M), The Bone Health Fund of the HKU Foundation, The KC Wong Education Foundation, Small Project Funding (201007176237), Matching Grant, Committee of Research and Conference Grants (CRCG) Grant, the Osteoporosis and Endocrine Research Fund, the Genomics Strategic Research Theme of The University of Hong Kong, Chinese University of Hong Kong, the Korea Health 21 Research & Development Project, the Korean Ministry of Health & Welfare, Republic of Korea (A010252), the Korea Healthcare Technology Research & Development Project, the Ministry for Health, Welfare and Family Affairs (A110536), The Netherlands Ministry of Health, Welfare and Sports Directorate of Long-Term Care, the World Anti-Doping Agency, the Danish Ministry of Culture, the Institute of Clinical Research of the University of Southern Denmark, the Chief Scientists Office of the Scottish Government (CZB/4/276), a Royal Society University Research Fellowship (to J.F.W.), the European Union Framework Program 6 EUROSPAN project (LSHG-CT-2006-018947), the European Union's Seventh Framework Programme (FP7/2007-2013; HEALTH-F2-2009-223004 PHASE), the Netherlands Organization of Scientific Research NWO Investments (175.010.2005.011 and 911-03-012), the Research Institute for Diseases in the Elderly (RIDE2; 014-93-015), the Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging (050-060-810), the German Bundesministerium fuer Forschung und Technology (01 AK 803 A-H and 01 IG 07015 G), the NIHR Biomedical Research Centre (grant to Guys' and St. Thomas' Hospitals and King's College London), the Chronic Disease Research Foundation, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Fonds de la Recherche en Santé Québec, The Lady Davis Institute, the Jewish General Hospital, the Ministère du Développement Economique, de l'Innovation et de l'Exportation du Quebec, the Swedish Sports Research Council (87/06), the Swedish Society of Medicine, the Kempe Foundation (JCK-1021), the Medical Faculty of Umeå University (ALFVLL:968:22-2005, ALFVL:-937-2006, ALFVLL:223:11-2007 and ALFVLL:78151-2009), the County Council of Västerbotten (Spjutspetsanslag; VLL:159:33-2007), the US National Cancer Institute, the Donald W. Reynolds Foundation, the Fondation Leducq, the Academy of Finland (126925, 121584, 124282, 129378 (Salve), 117787 (Gendi) and 41071 (Skidi)), the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds (9M048 for TeLeht), the Juho Vainio Foundation, the Paavo Nurmi Foundation, the Finnish Foundation of Cardiovascular Research, the Finnish Cultural Foundation, the Tampere Tuberculosis Foundation and the Emil Aaltonen Foundation (K08AR055688 to T.L.). A detailed list of acknowledgments by study is given in the Supplementary Note. The members of the GEFOS Consortium mourn the passing of co-author Philip Neil Sambrook, a good friend, respected colleague and outstanding research scientist in the prevention, treatment, epidemiology and genetics of osteoporosis.

Author information

Author notes

1. Karol Estrada, Unnur Styrkarsdottir, Evangelos Evangelou, Yi-Hsiang Hsu, Emma L Duncan, Evangelia E Ntzani and Ling Oei: These authors contributed equally to this work.
2. Unnur Thorsteinsdottir, Claes Ohlsson, David Karasik, J Brent Richards, Matthew A Brown, Kari Stefansson, André G Uitterlinden, Stuart H Ralston, John P A Ioannidis, Douglas P Kiel and Fernando Rivadeneira: These authors jointly directed this work.

Authors and Affiliations

1. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
   Karol Estrada, Ling Oei, Martha Castano-Betancourt, Lizbeth Herrera, Carolina Medina-Gómez, Joyce B J van Meurs, Huibert A P Pols, M Carola Zillikens, André G Uitterlinden & Fernando Rivadeneira
2. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
   Karol Estrada, Ling Oei, Najaf Amin, Yurii S Aulchenko, Martha Castano-Betancourt, Carolina Medina-Gómez, Joyce B J van Meurs, Albert Hofman, Huibert A P Pols, Cornelia M van Duijn, André G Uitterlinden & Fernando Rivadeneira
3. Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands
   Karol Estrada, Ling Oei, P Eline S lagboom, Martha Castano-Betancourt, Joyce B J van Meurs, Albert Hofman, André G Uitterlinden & Fernando Rivadeneira
4. deCODE Genetics, Reykjavik, Iceland
   Unnur Styrkarsdottir, Gudmar Thorleifsson, Hrefna Johannsdottir, Stefan Th Palsson, Unnur Thorsteinsdottir & Kari Stefansson
5. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
   Evangelos Evangelou, Evangelia E Ntzani & John P A Ioannidis
6. Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, USA
   Yi-Hsiang Hsu, Kannabiran Nandakumar, David Karasik & Douglas P Kiel
7. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
   Yi-Hsiang Hsu, Kannabiran Nandakumar, David Karasik & Douglas P Kiel
8. Human Genetics Group, University of Queensland Diamantina Institute, Brisbane, Queensland, Australia
   Emma L Duncan, Dana Willner, Paul J Leo, Graeme R Clark, Patrick Danoy & Matthew A Brown
9. Department of Endocrinology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
   Emma L Duncan
10. Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
    Omar M E Albagha, Nerea Alonso & Stuart H Ralston
11. Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK
    John P Kemp & David M Evans
12. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Daniel L Koller & Michael J Econs
13. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA
    Guo Li
14. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
    Ching-Ti Liu, Yanhua Zhou & L Adrienne Cupples
15. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Ryan L Minster & Candace M Kammerer
16. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
    Alireza Moayyeri, Stephen K Kaptoge, Robert Luben & Kay-Tee Khaw
17. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
    Alireza Moayyeri, Scott G Wilson, Frances M K Williams, Timothy D Spector & J Brent Richards
18. Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Liesbeth Vandenput, Joel Eriksson, Dan Mellström, Mattias Lorentzon & Claes Ohlsson
19. Australian Centre for Ecogenomics, University of Queensland, Brisbane, Queensland, Australia
    Dana Willner
20. Department of Medicine, The University of Hong Kong, Hong Kong, China
    Su-Mei Xiao & Annie Wai Chee Kung
21. Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong, China
    Su-Mei Xiao & Annie Wai Chee Kung
22. Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Laura M Yerges-Armstrong, Braxton D Mitchell, Alan R Shuldiner & Elizabeth A Streeten
23. Department of Human Genetics, Lady Davis Institute, McGill University, Montreal, Quebec, Canada
    Hou-Feng Zheng & J Brent Richards
24. School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
    Scott G Wilson, Joshua R Lewis, Kun Zhu & Richard L Prince
25. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
    Scott G Wilson, Joshua R Lewis, Kun Zhu & Richard L Prince
26. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
    James F Wilson
27. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
    James F Wilson
28. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
    Ville Aalto & Olli Raitakari
29. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
    Ville Aalto & Olli Raitakari
30. Department of Medical Rehabilitation, Oulu University Hospital and Institute of Health Sciences, Oulu, Finland
    Markku Alen
31. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    Aaron K Aragaki, Charles Kooperberg & Andrea Z Lacroix
32. Icelandic Heart Association, Kopavogur, Iceland
    Thor Aspelund, Kristin Siggeirsdottir, Albert V Smith & Vilmundur Gudnason
33. Faculty of Medicine, University of Iceland, Reykjavik, Iceland
    Thor Aspelund, Albert V Smith, Thorvaldur Ingvarsson, Gunnar Sigurdsson, Vilmundur Gudnason, Unnur Thorsteinsdottir & Kari Stefansson
34. Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
    Jacqueline R Center, Tuan V Nguyen & John A Eisman
35. Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia
    Jacqueline R Center, Tuan V Nguyen & John A Eisman
36. Department of Endocrinology, St. Vincent's Hospital, Sydney, New South Wales, Australia
    Jacqueline R Center & John A Eisman
37. Department of Orthopaedic Surgery, Medical School University of Thessalia, Larissa, Greece
    Zoe Dailiana
38. Translational Genomics Research Institute, Phoenix, Arizona, USA
    David J Duggan
39. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, USA
    Melissa Garcia & Tamara B Harris
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), Barcelona, Spain
    Natàlia Garcia-Giralt & Xavier Nogues
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, Quebec, Canada
    Sylvie Giroux & François Rousseau
42. Department of Public Health and Clinical Medicine, Umeå Unviersity, Umeå, Sweden
    Göran Hallmans
43. Division of Applied Medicine, Musculoskeletal Research Programme, University of Aberdeen, Aberdeen, UK
    Lynne J Hocking & David M Reid
44. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark
    Lise Bjerre Husted & Bente Lomholt Langdahl
45. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
    Karen A Jameson, Cyrus Cooper & Elaine M Dennison
46. Ufa Scientific Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa, Russia
    Rita Khusainova & Elza Khusnutdinova
47. Biological Department, Bashkir State University, Ufa, Russia
    Rita Khusainova & Elza Khusnutdinova
48. Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
    Ghi Su Kim, Seung Hun Lee & Jung-Min Koh
49. Department of Genetics and Biotechnology, Faculty of Biology, University of Athens, Athens, Greece
    Theodora Koromila & Panagoula Kollia
50. Department of Biochemistry and Experimental Medicine, The Children's Memorial Health Institute, Warsaw, Poland
    Marcin Kruk & Roman S Lorenc
51. Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland
    Marika Laaksonen
52. Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong, China
    Ping C Leung
53. Department of Internal Medicine, University of Florence, Florence, Italy
    Laura Masi & Maria Luisa Brandi
54. Department of Clinical Biochemistry, University of Ljubljana, Ljubljana, Slovenia
    Simona Mencej-Bedrac & Janja Marc
55. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
    Millan S Patel
56. Department of Endocrinology, University Medical Center, Ljubljana, Slovenia
    Janez Prezelj
57. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
    Lynda M Rose, Paul M Ridker & Daniel I Chasman
58. Department of Medicine, University of Cambridge, Cambridge, UK
    Serena Scollen
59. Department of Surgical and Perioperative Sciences, Umeå Unviersity, Umeå, Sweden
    Olle Svensson
60. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
    Stella Trompet & J Wouter Jukema
61. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
    Stella Trompet
62. Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University Graz, Graz, Austria
    Olivia Trummer & Barbara Obermayer-Pietsch
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
    Natasja M van Schoor
64. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
    Jean Woo
65. 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), Barcelona, Spain
    Susana Balcells & Roser Urreizti
66. Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland
    Brendan M Buckley
67. Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
    Sulin Cheng
68. Department of Orthopaedics and Traumatology, Kuopio University Hospital, Kuopio, Finland
    Sulin Cheng
69. Center for Clinical and Basic Research (CCBR)-Synarc, Ballerup, Denmark
    Claus Christiansen
70. Department of Nutrition and Dietetics, Harokopio University, Athens, Greece
    George Dedoussis
71. Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK
    Ian Ford
72. Department of Endocrinology, Odense University Hospital, Odense, Denmark
    Morten Frost
73. Clinical Institute, University of Southern Denmark, Odense, Denmark
    Morten Frost
74. Department of Medicine, McGill University, Montreal, Quebec, Canada
    David Goltzman
75. Department of Medicine, University of Cantabria, Santander, Spain
    Jesús González-Macías, José M Olmos & José A Riancho
76. Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla and Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain
    Jesús González-Macías, José M Olmos & José A Riancho
77. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
    Mika Kähönen
78. Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland
    Mika Kähönen
79. Department of Clinical Sciences, Clinical and Molecular Osteoporosis Research Unit, Lund University, Malmö, Sweden
    Magnus Karlsson
80. Department of Orthopaedics, Lund University, Malmö, Sweden
    Magnus Karlsson
81. Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    William D Leslie
82. Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands
    Paul Lips
83. Extramuraal Geneeskundig Onderzoek (EMGO) Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands
    Paul Lips
84. Department of Medical Sciences, University of Uppsala, Uppsala, Sweden
    Östen Ljunggren
85. Department of Pharmacology and Neuroscience, Umeå University, Umeå, Sweden
    Ulrika Pettersson-Kymmer
86. Harvard Medical School, Boston, Massachusetts, USA
    Paul M Ridker & Daniel I Chasman
87. Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec City, Quebec, Canada
    François Rousseau
88. The APOGEE-Net/CanGèneTest Network on Genetic Health Services and Policy, Université Laval, Québec City, Quebec, Canada
    François Rousseau
89. Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
    P Eline S lagboom
90. Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China
    Nelson L S Tang
91. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
    Nelson L S Tang
92. Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Wim Van Hul
93. Department of Medicine, Turku University Hospital, Turku, Finland
    Jorma Viikari
94. Department of Legal Medicine, University of Cantabria, Santander, Spain
    María T Zarrabeitia
95. Department of Human Genetics, McGill University, Montreal, Quebec, Canada
    Elin Grundberg, Tony Kwan, Dominique Verlaan & Tomi Pastinen
96. McGill University and Genome Québec Innovation Centre, Montreal, Quebec, Canada
    Elin Grundberg, Tony Kwan, Dominique Verlaan & Tomi Pastinen
97. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
    Elin Grundberg
98. Department of Orthopedic Surgery, Akureyri Hospital, Akureyri, Iceland
    Thorvaldur Ingvarsson
99. Institution of Health Science, University of Akureyri, Akureyri, Iceland
    Thorvaldur Ingvarsson
100. Department of Epidemiology and Biostatistics, Lady Davis Institute, McGill University, Montreal, Quebec, Canada
     Rui Li & J Brent Richards
101. Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
     Sjur Reppe & Kaare M Gautvik
102. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
     Jerome I Rotter
103. Department of Endocrinology and Metabolism, University Hospital, Reykjavik, Iceland
     Gunnar Sigurdsson
104. Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
     Andrew R Wood
105. Department of Clinical Biochemistry, Lovisenberg Deacon Hospital, Oslo, Norway
     Kaare M Gautvik
106. Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
     Kaare M Gautvik
107. Department of Medical Genetics, McGill University Health Centre, Montreal, Quebec, Canada
     Tomi Pastinen
108. Division of Genetics and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
     Soumya Raychaudhuri
109. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
     Soumya Raychaudhuri
110. Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
     Jane A Cauley
111. California Pacific Medical Center, San Francisco, California, USA
     Steven R Cummings
112. National Institute for Health and Research (NIHR), Musculoskeletal Biomedical Research Unit, University of Sheffield, Sheffield, UK
     Richard Eastell & Eugene McCloskey
113. Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA
     Rebecca D Jackson
114. Center for Clinical and Translational Science, The Ohio State University, Columbus, Ohio, USA
     Rebecca D Jackson
115. Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
     Graeme Jones
116. Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands
     J Wouter Jukema
117. Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
     J Wouter Jukema
118. Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland
     Terho Lehtimäki
119. Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland
     Terho Lehtimäki
120. Fimlab, Tampere, Finland
     Terho Lehtimäki
121. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
     Yongmei Liu
122. Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield, UK
     Eugene McCloskey
123. Rural Clinical School, The University of Queensland, Toowoomba, Queensland, Australia
     Geoffrey C Nicholson
124. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
     Ben A Oostra
125. Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
     Munro Peacock & Michael J Econs
126. Department of Medicine, University of Auckland, Auckland, New Zealand
     Ian R Reid
127. Department of Medicine, University of California, Davis, Sacramento, California, USA.,
     John Robbins
128. Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia
     Philip N Sambrook
129. Department of Psychiatry, The University of Hong Kong, Hong Kong, China
     Pak Chung Sham
130. Centre for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong, China
     Pak Chung Sham
131. Geriatric Research and Education Clinical Center (GRECC), Veterans Administration Medical Center, Baltimore, Maryland, USA
     Alan R Shuldiner & Elizabeth A Streeten
132. Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
     Frances A Tylavsky
133. MRC Epidemiology Unit Box 285, MRC, Cambridge, UK
     Nick J Wareham
134. Framingham Heart Study, Framingham, Massachusetts, USA
     L Adrienne Cupples
135. Department of Medicine, University of Washington, Seattle, Washington, USA
     Bruce M Psaty
136. Department of Epidemiology, University of Washington, Seattle, Washington, USA
     Bruce M Psaty
137. Deparment of Health Services, University of Washington, Seattle, Washington, USA
     Bruce M Psaty
138. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA
     Bruce M Psaty
139. Medicine Box 157, University of Cambridge, Cambridge, UK
     Jonathan Reeve
140. Department of Medicine, Lady Davis Institute, McGill University, Montreal, Quebec, Canada
     J Brent Richards
141. Stanford Prevention Research Center, Stanford University, Stanford, California, USA
     John P A Ioannidis

Authors

1. Karol Estrada
2. Unnur Styrkarsdottir
3. Evangelos Evangelou
4. Yi-Hsiang Hsu
5. Emma L Duncan
6. Evangelia E Ntzani
7. Ling Oei
8. Omar M E Albagha
9. Najaf Amin
10. John P Kemp
11. Daniel L Koller
12. Guo Li
13. Ching-Ti Liu
14. Ryan L Minster
15. Alireza Moayyeri
16. Liesbeth Vandenput
17. Dana Willner
18. Su-Mei Xiao
19. Laura M Yerges-Armstrong
20. Hou-Feng Zheng
21. Nerea Alonso
22. Joel Eriksson
23. Candace M Kammerer
24. Stephen K Kaptoge
25. Paul J Leo
26. Gudmar Thorleifsson
27. Scott G Wilson
28. James F Wilson
29. Ville Aalto
30. Markku Alen
31. Aaron K Aragaki
32. Thor Aspelund
33. Jacqueline R Center
34. Zoe Dailiana
35. David J Duggan
36. Melissa Garcia
37. Natàlia Garcia-Giralt
38. Sylvie Giroux
39. Göran Hallmans
40. Lynne J Hocking
41. Lise Bjerre Husted
42. Karen A Jameson
43. Rita Khusainova
44. Ghi Su Kim
45. Charles Kooperberg
46. Theodora Koromila
47. Marcin Kruk
48. Marika Laaksonen
49. Andrea Z Lacroix
50. Seung Hun Lee
51. Ping C Leung
52. Joshua R Lewis
53. Laura Masi
54. Simona Mencej-Bedrac
55. Tuan V Nguyen
56. Xavier Nogues
57. Millan S Patel
58. Janez Prezelj
59. Lynda M Rose
60. Serena Scollen
61. Kristin Siggeirsdottir
62. Albert V Smith
63. Olle Svensson
64. Stella Trompet
65. Olivia Trummer
66. Natasja M van Schoor
67. Jean Woo
68. Kun Zhu
69. Susana Balcells
70. Maria Luisa Brandi
71. Brendan M Buckley
72. Sulin Cheng
73. Claus Christiansen
74. Cyrus Cooper
75. George Dedoussis
76. Ian Ford
77. Morten Frost
78. David Goltzman
79. Jesús González-Macías
80. Mika Kähönen
81. Magnus Karlsson
82. Elza Khusnutdinova
83. Jung-Min Koh
84. Panagoula Kollia
85. Bente Lomholt Langdahl
86. William D Leslie
87. Paul Lips
88. Östen Ljunggren
89. Roman S Lorenc
90. Janja Marc
91. Dan Mellström
92. Barbara Obermayer-Pietsch
93. José M Olmos
94. David M Reid
95. José A Riancho
96. Paul M Ridker
97. François Rousseau
98. P Eline S lagboom
99. Nelson L S Tang
100. Roser Urreizti
101. Wim Van Hul
102. Jorma Viikari
103. María T Zarrabeitia
104. Yurii S Aulchenko
105. Martha Castano-Betancourt
106. Elin Grundberg
107. Lizbeth Herrera
108. Hrefna Johannsdottir
109. Tony Kwan
110. Rui Li
111. Robert Luben
112. Carolina Medina-Gómez
113. Stefan Th Palsson
114. Sjur Reppe
115. Jerome I Rotter
116. Gunnar Sigurdsson
117. Joyce B J van Meurs
118. Dominique Verlaan
119. Frances M K Williams
120. Andrew R Wood
121. Yanhua Zhou
122. Kaare M Gautvik
123. Tomi Pastinen
124. Soumya Raychaudhuri
125. Jane A Cauley
126. Daniel I Chasman
127. Graeme R Clark
128. Steven R Cummings
129. Patrick Danoy
130. Elaine M Dennison
131. Richard Eastell
132. John A Eisman
133. Vilmundur Gudnason
134. Albert Hofman
135. Rebecca D Jackson
136. Graeme Jones
137. J Wouter Jukema
138. Kay-Tee Khaw
139. Terho Lehtimäki
140. Yongmei Liu
141. Mattias Lorentzon
142. Eugene McCloskey
143. Braxton D Mitchell
144. Kannabiran Nandakumar
145. Geoffrey C Nicholson
146. Ben A Oostra
147. Munro Peacock
148. Huibert A P Pols
149. Richard L Prince
150. Olli Raitakari
151. Ian R Reid
152. John Robbins
153. Philip N Sambrook
154. Pak Chung Sham
155. Alan R Shuldiner
156. Frances A Tylavsky
157. Cornelia M van Duijn
158. Nick J Wareham
159. L Adrienne Cupples
160. Michael J Econs
161. David M Evans
162. Tamara B Harris
163. Annie Wai Chee Kung
164. Bruce M Psaty
165. Jonathan Reeve
166. Timothy D Spector
167. Elizabeth A Streeten
168. M Carola Zillikens
169. Unnur Thorsteinsdottir
170. Claes Ohlsson
171. David Karasik
172. J Brent Richards
173. Matthew A Brown
174. Kari Stefansson
175. André G Uitterlinden
176. Stuart H Ralston
177. John P A Ioannidis
178. Douglas P Kiel
179. Fernando Rivadeneira

Contributions

This work was done under the auspices of the European Commission–sponsored Genetic Factors for Osteoporosis (GEFOS) consortium.

Study-specific design and management were performed by U.S., M.A., L.M., J.P., S.B., M.L.B., B.M.B., C. Christiansen, C. Cooper, G.D., I.F., M.F., D.G., J.G.-M., M. Kähönen, M. Karlsson, J.-M.K., P.K., B.L.L., W.D.L., P.L., Ö.L., R.S.L., J.M., D.M., J.M.O., U.P.-K., J.A.R., P.M.R., F. Rousseau, P.E.S., N.L.S.T., R.U., W.V.H., J.V., M.T.Z., K.M.G., T.P., D.I.C., S.R.C., R.E., J.A.E., V.G., A.H., R.D.J., G.J., J.W.J., K.-T.K., T.L., M. Lorentzon, E.M., B.D.M., G.C.N., M.P., H.A.P.P., R.L.P., O.R., I.R.R., P.N.S., P.C.S., A.R.S., F.A.T., C.M.v.D., N.J.W., L.A.C., M.J.E., T.B.H., A.W.C.K., B.M.P., J. Reeve, T.D.S., E.A.S., M.C.Z., U.T., C.O., J.B.R., M.A.B., K. Stefansson, A.G.U., S.H.R., J.P.A.I., D.P.K. and F. Rivadeneira. Study-specific genotyping was performed by K.E., U.S., E.L.D., L.O., L.V., S.-M.X., A.K.A., D.J.D., S.G., R.K., C.K., A.Z.L., J.R.L., S.M., S.M.-B., S.S., S.T., O.T., S.C., E.K., J.M., B.O.-P., Y.S.A., E.G., L.H., H.J., T. Kwan, R. Luben, C.M.-G., S.T.P., S. Reppe, J.I.R., J.B.J.v.M., D.V., K.M.G., D.I.C., G.R.C., P.D., R.D.J., T.L., Y.L., M. Lorentzon, R.L.P., N.J.W., L.A.C., C.O., M.A.B., A.G.U. and F. Rivadeneira. Study-specific phenotyping was performed by U.S., E.L.D., O.M.E.A., A.M., S.-M.X., N. Alonso, S.K.K., S.G.W., A.K.A., T.A., J.R.C., Z.D., N.G.-G., S.G., G.H., L.B.H., K.A.J., G.K., G.S.K., C.K., T. Koromila, M. Kruk, M. Laaksonen, A.Z.L., S.H.L., P.C.L., L.M., X.N., J.P., L.M.R., K. Siggeirsdottir, O.S., N.M.v.S., J.W., K.Z., M.L.B., C. Christiansen, M.F., M. Kähönen, M. Karlsson, J.-M.K., Ö.L., J.M., D.M., B.O.-P., J.M.O., U.P.-K., D.M.R., J.A.R., P.M.R., F. Rousseau, W.V.H., J.V., M.C.-B., E.G., T.I., R. Luben, S. Reppe, G.S., J.B.J.v.M., D.V., F.M.K.W., K.M.G., J.A.C., D.I.C., E.M.D., R.E., J.A.E., V.G., A.H., R.D.J., G.J., Y.L., M. Lorentzon, E.M., G.C.N., B.A.O., M.P., H.A.P.P., R.L.P., O.R., I.R.R., J. Robbins, P.N.S., C.M.v.D., M.J.E., J. Reeve, E.A.S., M.C.Z., C.O., M.A.B., A.G.U., D.P.K. and F. Rivadeneira. Study-specific data analysis were performed by K.E., U.S., E.E., Y.-H.H., E.L.D., E.E.N., L.O., O.M.E.A., N. Amin, J.P.K., D.L.K., G.L., C.L., R.L.M., A.M., L.V., D.W., S.-M.X., L.M.Y.-A., H.-F.Z., J.E., C.M.K., S.K.K., P.J.L., G.T., J.F.W., V.A., A.K.A., T.A., J.R.C., G.H., L.J.H., C.K., T. Koromila, A.Z.L., S.M.-B., T.V.N., M.S.P., J.P., L.M.R., A.V.S., O.S., S.T., S.C., J.M., B.O.-P., U.P.-K., R. Li, R. Luben, S. Reppe, J.I.R., A.R.W., Y.Z., S. Raychaudhuri, D.I.C., J.A.E., R.D.J., T.L., K.N., O.R., D.M.E., D.K., J.B.R., M.A.B., J.P.A.I., D.P.K. and F. Rivadeneira. Analysis plan design was performed by K.E., E.E., U.S., D.K., D.P.K., J.P.A.I. and F. Rivadeneira. K.E., E.E., Y.-H.H. and E.E.N. carried out meta-analyses. K.E., E.E. and A.R.W. determined gene-by-gene interaction. Risk modeling and analysis of secondary signals were performed by K.E. and F. Rivadeneira. Expression QTLs were analyzed by U.S., G.T., E.G., S. Reppe, K.M.G. and T.P. Y.-H.H. performed functional SNP prediction. GRAIL was carried out by K.E., E.L.D., D.W. and S. Raychaudhuri. Standardization of phenotype and genotype replication data sets was performed by K.E., U.S., E.E., E.L.D., L.O., G.T., L.H. and C.M.-G. Interpretation of results was carried out by K.E., U.S., E.E., Y.-H.H., E.L.D., E.E.N., L.O., O.M.E.A., N. Amin, D.L.K., C.-T.L., R.L.M., A.M., L.V., D.W., S.-M.X., L.M.Y.-A., J.E., C.M.K., S.K.K., A.W.C.K., J. Reeve, M.C.Z., C.O., D.K., J.B.R., M.A.B., A.G.U., S.H.R., J.P.A.I., D.P.K. and F. Rivadeneira. The manuscript draft was prepared by K.E., U.S., E.E., Y.-H.H., E.L.D., E.E.N., L.O., O.M.E.A., A.M., C.O., D.K., J.B.R., M.A.B., A.G.U., S.H.R., J.P.A.I., D.P.K. and F. Rivadeneira. The steering committee for GEFOS includes U.S., E.E., U.T., A.G.U., S.H.R., J.P.A.I. and F. Rivadeneira.

Corresponding author

Correspondence toFernando Rivadeneira.

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Competing interests

The coauthors affiliated with deCODE genetics in Reykjavik, Iceland, hold stock options in that company.

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Estrada, K., Styrkarsdottir, U., Evangelou, E. et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.Nat Genet 44, 491–501 (2012). https://doi.org/10.1038/ng.2249

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• Received: 07 October 2011
• Accepted: 16 March 2012
• Published: 15 April 2012
• Issue date: May 2012
• DOI: https://doi.org/10.1038/ng.2249