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

Estrada, Karol; Styrkarsdottir, Unnur; Evangelou, Evangelos; Hsu, Yi-Hsiang; Duncan, Emma L.; Ntzani, Evangelia E.; Oei, Ling; Albagha, Omar M. E.; Amin, Najaf; Kemp, John P.; Koller, Daniel L.; Li, Guo; Liu, Ching-Ti; Minster, Ryan L.; Moayyeri, Alireza; Vandenput, Liesbeth; Willner, Dana; Xiao, Su-Mei; Yerges-Armstrong, Laura M.; Zheng, Hou-Feng; Alonso, Nerea; Eriksson, Joel; Kammerer, Candace M.; Kaptoge, Stephen K.; Leo, Paul J.; Thorleifsson, Gudmar; Wilson, Scott G.; Wilson, James F.; Aalto, Ville; Alen, Markku; Aragaki, Aaron K.; Aspelund, Thor; Center, Jacqueline R.; Dailiana, Zoe; Duggan, David J.; Garcia, Melissa; Garcia-Giralt, Natàlia; Giroux, Sylvie; Hallmans, Göran; Hocking, Lynne J.; Husted, Lise Bjerre; Jameson, Karen A.; Khusainova, Rita; Kim, Ghi Su; Kooperberg, Charles; Koromila, Theodora; Kruk, Marcin; Laaksonen, Marika; Lacroix, Andrea Z.; Lee, Seung Hun; Leung, Ping C.; Lewis, Joshua R.; Masi, Laura; Mencej-Bedrac, Simona; Nguyen, Tuan V.; Nogues, Xavier; Patel, Millan S.; Prezelj, Janez; Rose, Lynda M.; Scollen, Serena; Siggeirsdottir, Kristin; Smith, Albert V.; Svensson, Olle; Trompet, Stella; Trummer, Olivia; van Schoor, Natasja M.; Woo, Jean; Zhu, Kun; Balcells, Susana; Brandi, Maria Luisa; Buckley, Brendan M.; Cheng, Sulin; Christiansen, Claus; Cooper, Cyrus; Dedoussis, George; Ford, Ian; Frost, Morten; Goltzman, David; González-Macías, Jesús; Kähönen, Mika; Karlsson, Magnus; Khusnutdinova, Elza; Koh, Jung-Min; Kollia, Panagoula; Langdahl, Bente Lomholt; Leslie, William D.; Lips, Paul; Ljunggren, Östen; Lorenc, Roman S.; Marc, Janja; Mellström, Dan; Obermayer-Pietsch, Barbara; Olmos, José M.; Pettersson-Kymmer, Ulrika; Reid, David M.; Riancho, José A.; Ridker, Paul M.; Rousseau, François; Slagboom, P. Eline; Tang, Nelson L. S.; Urreizti, Roser; Van Hul, Wim; Viikari, Jorma; Zarrabeitia, María T.; Aulchenko, Yurii S.; Castano-Betancourt, Martha; Grundberg, Elin; Herrera, Lizbeth; Ingvarsson, Thorvaldur; Johannsdottir, Hrefna; Kwan, Tony; Li, Rui; Luben, Robert; Medina-Gómez, Carolina; Palsson, Stefan Th; Reppe, Sjur; Rotter, Jerome I.; Sigurdsson, Gunnar; van Meurs, Joyce B. J.; Verlaan, Dominique; Williams, Frances M. K.; Wood, Andrew R.; Zhou, Yanhua; Gautvik, Kaare M.; Pastinen, Tomi; Raychaudhuri, Soumya; Cauley, Jane A.; Chasman, Daniel I.; Clark, Graeme R.; Cummings, Steven R.; Danoy, Patrick; Dennison, Elaine M.; Eastell, Richard; Eisman, John A.; Gudnason, Vilmundur; Hofman, Albert; Jackson, Rebecca D.; Jones, Graeme; Jukema, J. Wouter; Khaw, Kay-Tee; Lehtimäki, Terho; Liu, Yongmei; Lorentzon, Mattias; McCloskey, Eugene; Mitchell, Braxton D.; Nandakumar, Kannabiran; Nicholson, Geoffrey C.; Oostra, Ben A.; Peacock, Munro; Pols, Huibert A. P.; Prince, Richard L.; Raitakari, Olli; Reid, Ian R.; Robbins, John; Sambrook, Philip N.; Sham, Pak Chung; Shuldiner, Alan R.; Tylavsky, Frances A.; van Duijn, Cornelia M.; Wareham, Nick J.; Cupples, L. Adrienne; Econs, Michael J.; Evans, David M.; Harris, Tamara B.; Kung, Annie Wai Chee; Psaty, Bruce M.; Reeve, Jonathan; Spector, Timothy D.; Streeten, Elizabeth A.; Zillikens, M. Carola; Thorsteinsdottir, Unnur; Ohlsson, Claes; Karasik, David; Richards, J. Brent; Brown, Matthew A.; Stefansson, Kari; Uitterlinden, André G.; Ralston, Stuart H.; Ioannidis, John P. A.; Kiel, Douglas P.; Rivadeneira, Fernando

Affiliations

¹Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

²Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

³Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.

⁴deCODE Genetics, Reykjavik, Iceland.

⁵Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

⁶Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, USA.

⁷Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

⁸Human Genetics Group, University of Queensland Diamantina Institute, Brisbane, Queensland, Australia.

⁹Department of Endocrinology, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia.

¹⁰Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

¹¹Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.

¹²Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.

¹³Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.

¹⁴Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

¹⁵Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

¹⁶Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

¹⁷Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK.

¹⁸Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

¹⁹Australian Centre for Ecogenomics, University of Queensland, Brisbane, Queensland, Australia.

²⁰Department of Medicine, The University of Hong Kong, Hong Kong, China.

²¹Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong, China.

²²Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.

²³Department of Human Genetics, Lady Davis Institute, McGill University, Montreal, Quebec, Canada.

²⁴School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.

²⁵Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.

²⁶Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.

²⁷MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

²⁸Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.

²⁹Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

³⁰Department of Medical Rehabilitation, Oulu University Hospital and Institute of Health Sciences, Oulu, Finland.

³¹Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

³²Icelandic Heart Association, Kopavogur, Iceland.

³³Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

³⁴Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.

³⁵Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

³⁶Department of Endocrinology, St. Vincent’s Hospital, Sydney, New South Wales, Australia.

³⁷Department of Orthopaedic Surgery, Medical School University of Thessalia, Larissa, Greece.

³⁸Translational Genomics Research Institute, Phoenix, Arizona, USA.

³⁹Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, USA.

⁴⁰Department 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.

⁴¹Unité 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.

⁴²Department of Public Health and Clinical Medicine, Umeå Unviersity, Umeå, Sweden.

⁴³Musculoskeletal Research Programme, Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.

⁴⁴Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C, Denmark.

⁴⁵MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.

⁴⁶Ufa Scientific Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa, Russia.

⁴⁷Biological Department, Bashkir State University, Ufa, Russia.

⁴⁸Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

⁴⁹Department of Genetics and Biotechnology, Faculty of Biology, University of Athens, Athens, Greece.

⁵⁰Department of Biochemistry and Experimental Medicine, The Children’s Memorial Health Institute, Warsaw, Poland.

⁵¹Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.

⁵²Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong, China.

⁵³Department of Internal Medicine, University of Florence, Florence, Italy.

⁵⁴Department of Clinical Biochemistry, University of Ljubljana, Ljubljana, Slovenia.

⁵⁵Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.

⁵⁶Department of Endocrinology, University Medical Center, Ljubljana, Slovenia.

⁵⁷Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

⁵⁸Department of Medicine, University of Cambridge, Cambridge, UK.

⁵⁹Department of Surgical and Perioperative Sciences, Umeå Unviersity, Umeå, Sweden.

⁶⁰Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.

⁶¹Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.

⁶²Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University Graz, Graz, Austria.

⁶³Department of Epidemiology and Biostatistics, Extramuraal Geneeskundig Onderzoek (EMGO) Institute for Health and Care Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands.

⁶⁴Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

⁶⁵Department 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.

⁶⁶Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.

⁶⁷Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

⁶⁸Department of Orthopaedics and Traumatology, Kuopio University Hospital, Kuopio, Finland.

⁶⁹Center for Clinical and Basic Research (CCBR)-Synarc, Ballerup, Denmark.

⁷⁰Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.

⁷¹Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.

⁷²Department of Endocrinology, Odense University Hospital, Odense, Denmark.

⁷³Clinical Institute, University of Southern Denmark, Odense, Denmark.

⁷⁴Department of Medicine, McGill University, Montreal, Quebec, Canada.

⁷⁵Department of Medicine, University of Cantabria, Santander, Spain.

⁷⁶Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla and Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Spain.

⁷⁷Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.

⁷⁸Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland.

⁷⁹Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.

⁸⁰Department of Orthopaedics, Lund University, Malmö, Sweden.

⁸¹Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

⁸²Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.

⁸³Extramuraal Geneeskundig Onderzoek (EMGO) Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.

⁸⁴Department of Medical Sciences, University of Uppsala, Uppsala, Sweden.

⁸⁵Department of Pharmacology and Neuroscience, Umeå University, Umeå, Sweden.

⁸⁶Harvard Medical School, Boston, Massachusetts, USA.

⁸⁷Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec City, Quebec, Canada.

⁸⁸The APOGEE-Net/CanGèneTest Network on Genetic Health Services and Policy, Université Laval, Québec City, Quebec, Canada.

⁸⁹Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

⁹⁰Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.

⁹¹Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

⁹²Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.

⁹³Department of Medicine, Turku University Hospital, Turku, Finland.

⁹⁴Department of Legal Medicine, University of Cantabria, Santander, Spain.

⁹⁵Department of Human Genetics, McGill University, Montreal, Quebec, Canada.

⁹⁶McGill University and Genome Québec Innovation Centre, Montreal, Quebec, Canada.

⁹⁷Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

⁹⁸Department of Orthopedic Surgery, Akureyri Hospital, Akureyri, Iceland.

⁹⁹Institution of Health Science, University of Akureyri, Akureyri, Iceland.

¹⁰⁰Department of Epidemiology and Biostatistics, Lady Davis Institute, McGill University, Montreal, Quebec, Canada.

¹⁰¹Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.

¹⁰²Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

¹⁰³Department of Endocrinology and Metabolism, University Hospital, Reykjavik, Iceland.

¹⁰⁴Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.

¹⁰⁵Department of Clinical Biochemistry, Lovisenberg Deacon Hospital, Oslo, Norway.

¹⁰⁶Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

¹⁰⁷Department of Medical Genetics, McGill University Health Centre, Montreal, Quebec, Canada.

¹⁰⁸ Division of Genetics and Rheumatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.

¹⁰⁹Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.

¹¹⁰Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

¹¹¹California Pacific Medical Center, San Francisco, California, USA.

¹¹²National Institute for Health and Research (NIHR), Musculoskeletal Biomedical Research Unit, University of Sheffield, Sheffield, UK.

¹¹³Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.

¹¹⁴Center for Clinical and Translational Science, The Ohio State University, Columbus, Ohio, USA.

¹¹⁵Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.

¹¹⁶Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands.

¹¹⁷Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.

¹¹⁸Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland.

¹¹⁹Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.

¹²⁰Fimlab, Tampere, Finland.

¹²¹Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

¹²²Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield, UK.

¹²³Rural Clinical School, The University of Queensland, Toowoomba, Queensland, Australia.

¹²⁴Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.

¹²⁵Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

¹²⁶Department of Medicine, University of Auckland, Auckland, New Zealand.

¹²⁷Department of Medicine, University of California, Davis, Sacramento, California, USA.

¹²⁸Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia.

¹²⁹Department of Psychiatry, The University of Hong Kong, Hong Kong, China.

¹³⁰Centre for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong, China.

¹³¹Geriatric Research and Education Clinical Center (GRECC), Veterans Administration Medical Center, Baltimore, Maryland, USA.

¹³²Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

¹³³MRC Epidemiology Unit Box 285, MRC, Cambridge, UK.

¹³⁴Framingham Heart Study, Framingham, Massachusetts, USA.

¹³⁵Department of Medicine, University of Washington, Seattle, Washington, USA.

¹³⁶Department of Epidemiology, University of Washington, Seattle, Washington, USA.

¹³⁷Deparment of Health Services, University of Washington, Seattle, Washington, USA.

¹³⁸Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.

¹³⁹Medicine Box 157, University of Cambridge, Cambridge, UK.

¹⁴⁰Department of Medicine, Lady Davis Institute, McGill University, Montreal, Quebec, Canada.

¹⁴¹Stanford Prevention Research Center, Stanford University, Stanford, California, USA.

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.

Links

DOI: 10.1038/ng.2249

PubMed: 22504420

WoS: 000303416300007

History

Received: 2011-10-07

Accepted: 2012-03-16

Online: 2012-04-15

Cited Works (7)

Year	Entry
2003	Duan Y, Beck TJ, Wang X-F, Seeman E. Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J Bone Miner Res. October 2003;18(10):1766-1774.
1999	Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH III, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD; Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA. October 13, 1999;282(14):1344-1352.
2006	Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SAA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D; Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. NEJM. February 16, 2006;354(7):669-683.
2005	Johnell O, Kanis JA, Oden A, Johansson H, De Laet C, Delmas P, Eisman JA, Fujiwara S, Kroger H, Mellstrom D, Meunier PJ, Melton LJ III, O'Neill T, Pols H, Reeve J, Silman A, Tenenhouse A. Predictive value of BMD for hip and other fractures. J Bone Miner Res. July 2005;20(7):1185-1194.
2001	Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo P, Fu Y-H, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan JT. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot–containing protein. Am J Hum Genet. March 2001;68(3):577-589.
2007	Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, Burckhardt P, Cooper C, Christiansen C, Cummings S, Eisman JA, Fujiwara S, Glüer C, Goltzman D, Hans D, Krieg M-A, La Croix A, McCloskey E, Mellstrom D, Melton LJ, Pols H, Reeve J, Sanders K, Schott A-M, Silman A, Torgerson D, van Staa T, Watts NB, Yoshimura N. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int. August 2007;18(8):1033-1046.
2007	Burge R, Dawson‐Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis‐related fractures in the United States, 2005–2025. J Bone Miner Res. March 2007;22(3):465-475.

Cited By (39)

Year	Entry
2018	Trajanoska K, Morris JA, Oei L, Zheng H-F, Evans DM, Kiel DP, Ohlsson C, Richards JB, Rivadeneira F; GEFOS/GENOMOS consortium; 23andMe research team. Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study. BMJ. August 29, 2018;362:k3225.
2020	Bai W-Y, Wang L, Ying Z-M, Hu B, Xu L, Zhang G-Q, Cong P-K, Zhu X, Zou W, Zheng H-F. Identification of PIEZO1 polymorphisms for human bone mineral density. Bone. April 2020;133:115247.
2020	Ascenzi M-G. Theoretical mathematics, polarized light microscopy and computational models in healthy and pathological bone. Bone. May 2020;134:115295.
2021	Frysz M, Baird D, Gregory JS, Aspden RM, Lane NE, Ohlsson C, Pettersson-Kymmer U, Karasik D, Tobias JH, Paternoster L. The influence of adult hip shape genetic variants on adolescent hip shape: findings from a population-based DXA study. Bone. February 2021;143:115792.
2021	Fuggle NR, Westbury LD, Bevilacqua G, Titcombe P, Ó. Breasail M, Harvey NC, Dennison EM, Cooper C, Ward KA. Level and change in bone microarchitectural parameters and their relationship with previous fracture and established bone mineral density loci. Bone. June 2021;147:115937.
2022	Zhang J, Tong Y, Liu Y, Lin M, Xiao Y, Liu C. Mechanical loading attenuated negative effects of nucleotide analogue reverse-transcriptase inhibitor TDF on bone repair via Wnt/β-catenin pathway. Bone. August 2022;161:116449.
2013	Boskey AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. BoneKEy Rep. December 2013;2:447.
2020	Liu H, Zhao H, Lin H, Li Z, Xue H, Zhang Y, Lu J. Relationship of COL9A1 and SOX9 genes with genetic susceptibility of postmenopausal osteoporosis. Calcif Tiss Int. March 2020;106(3):248-255.
2020	Hendrickx G, Boudin E, Verbeek M, Fransen E, Mortier G, Van Hul W. WNT16 requires Gα subunits as intracellular partners for both its canonical and non-canonical WNT signalling activity in osteoblasts. Calcif Tiss Int. March 2020;106(3):294-302.
2020	Tanaka K-i, Kanazawa I, Richards JB, Goltzman D, Sugimoto T. Modulators of Fam210a and roles of Fam210a in the function of myoblasts. Calcif Tiss Int. May 2020;106(5):533-540.
2020	Törnqvist AE, Grahnemo L, Nilsson KH, Funck-Brentano T, Ohlsson C, Movérare-Skrtic S. Wnt16 overexpression in osteoblasts increases the subchondral bone mass but has no impact on osteoarthritis in young adult female mice. Calcif Tiss Int. July 2020;107(1):31-40.
2020	Wu Q, Nasoz F, Jung J, Bhattarai B, Han MV. Machine learning approaches for fracture risk assessment: a comparative analysis of genomic and phenotypic data in 5130 older men. Calcif Tiss Int. October 2020;107(4):353-361.
2017	Kim SW, Lu Y, Williams EA, Lai F, Lee JY, Enishi T, Balani DH, Ominsky MS, Ke HZ, Kronenberg HM, Wein MN. Sclerostin antibody administration converts bone lining cells into active osteoblasts. J Bone Miner Res. May 2017;32(5):892-901.
2020	Manousaki D, Kämpe A, Forgetta V, Makitie RE, Bardai G, Belisle A, Li R, Andersson S, Makitie O, Rauch F, Richards JB. Increased burden of common risk alleles in children with a significant fracture history. J Bone Miner Res. May 2020;35(5):875-882.
2020	Zheng J, Brion M, Kemp JP, Warrington NM, Borges M, Hemani G, Richardson TG, Rasheed H, Qiao Z, Haycock P, Ala‐Korpela M, Smith GD, Tobias JH, Evans DM. The effect of plasma lipids and lipid‐lowering interventions on bone mineral density: a Mendelian randomization study. J Bone Miner Res. July 2020;35(7):1224-1235.
2020	Rivadeneira F, Westendorf JJ. Bringing genomic discoveries to the clinic: integrating omic data into the musculoskeletal field through international teamwork and collaboration. J Bone Miner Res. September 2020;35(9):1623-1625.
2020	Kiel DP, Kemp JP, Rivadeneira F, Westendorf JJ, Karasik D, Duncan EL, Imai Y, Müller R, Flannick J, Bonewald L, Burtt N. The musculoskeletal knowledge portal: making omics data useful to the broader scientific community. J Bone Miner Res. September 2020;35(9):1626-1633.
2020	Manousaki D, Forgetta V, Keller‐Baruch J, Zhao K, Greenwood CMT, Mooser V, Bassett JHD, Leslie WD, Richards JB. A polygenic risk score as a risk factor for medication‐associated fractures. J Bone Miner Res. October 2020;35(10):1935-1941.
2021	Lewis JR, Voortman T, Ioannidis JP. Evaluating and strengthening the evidence for nutritional bone research: ready to break new ground? J Bone Miner Res. February 2021;36(2):219-226.
2021	Yau MS, Kuipers AL, Price R, Nicolas A, Tajuddin SM, Handelman SK, Arbeeva L, Chesi A, Hsu Y, Liu C, Karasik D, Zemel BS, Grant SF, Jordan JM, Jackson RD, Evans MK, Harris TB, Zmuda JM, Kiel DP. A meta‐analysis of the transferability of bone mineral density genetic loci associations from European to African ancestry populations. J Bone Miner Res. March 2021;36(3):469-479.
2021	Zhang X, Xu H, Li GHY, Long MT, Cheung C, Vasan RS, Hsu Y, Kiel DP, Liu C. Metabolomics insights into osteoporosis through association with bone mineral density. J Bone Miner Res. April 2021;36(4):729-738.
2021	Mun SH, Jastrzebski S, Kalinowski J, Zeng S, Oh B, Bae S, Eugenia G, Khan NM, Drissi H, Zhou P, Shin B, Lee S-K, Lorenzo J, Park-Min K-H. Sexual dimorphism in differentiating osteoclast precursors demonstrates enhanced inflammatory pathway activation in female cells. J Bone Miner Res. June 2021;36(6):1104-1116.
2022	Kaya S, Schurman CA, Dole NS, Evans DS, Alliston T. Prioritization of genes relevant to bone fragility through the unbiased integration of aging mouse bone transcriptomics and human GWAS analyses. J Bone Miner Res. April 2022;37(4):804-817.
2022	Zhu D-L, Chen X-F, Zhou X-R, Hu S-Y, Tuo X-M, Hao R-H, Dong S-S, Jiang F, Rong Y, Yang T-L, Yang Z, Guo Y. An osteoporosis susceptibility allele at 11p15 regulates SOX6 expression by modulating TCF4 chromatin binding. J Bone Miner Res. June 2022;37(6):1147-1155.
2022	Teufel S, Wolff L, König U, Kobayashi A, Behringer R, Hartmann C. Mice lacking Wnt9a or Wnt4 are prone to develop spontaneous osteoarthritis with age and display alteration in either the trabecular or cortical bone compartment. J Bone Miner Res. July 2022;37(7):1335-1351.
2022	Lu T, Forgetta V, Greenwood CMT, Richards JB. Identifying causes of fracture beyond bone mineral density: evidence from human genetics. J Bone Miner Res. August 2022;37(8):1592-1602.
2023	Hassan N, Gregson CL, Tang H, van der Kamp M, Leo P, McInerney-Leo AM, Zheng J, Brandi ML, Tang JCY, Fraser W, Stone MD, Grundberg E, Brown MA, Duncan EL, Tobias JH; Anglo-Australasian Genetics Consortium. Rare and common variants in GALNT3 may affect bone mass independently of phosphate metabolism. J Bone Miner Res. June 2023;38(5):678-691.
2023	Stein M, Elefteriou F, Busse B, Fiedler IA, Kwon RY, Farrell E, Ahmad M, Ignatius A, Grover L, Geris L, Tuckermann J. Why animal experiments are still indispensable in bone research: a statement by the European Calcified Tissue Society. J Bone Miner Res. August 2023;38(8):1045-1061.
2020	Nethander M, Pettersson-Kymmer U, Vandenput L, Lorentzon M, Karlsson M, Mellström D, Ohlsson C. BMD-related genetic risk scores predict site-specific fractures as well as trabecular and cortical bone microstructure. J Clin Endocrinol Metab. April 2020;105(4):dgaa082.
2017	Kemp JP, Morris JA, Medina-Gomez C, Forgetta V, Warrington NM, Youlten SE, Zheng J, Gregson CL, Grundberg E, Trajanoska K, Logan JG, Pollard AS, Sparkes PC, Ghirardello EJ, Allen R, Leitch VD, Butterfield NC, Komla-Ebri D, Adoum A-T, Curry KF, White JK, Kussy F, Greenlaw KM, Xu C, Harvey NC, Cooper C, Adams DJ, Greenwood CMT, Maurano MT, Kaptoge S, Rivadeneira F, Tobias JH, Croucher PI, Ackert-Bicknell CL, Bassett JHD, Williams GR, Richards JB, Evans DM. Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis. Nat Genet. October 2017;49(10):1468-1475.
2013	Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. February 2013;19(2):179-192.
2015	Zheng H-F, Forgetta V, Hsu Y-H, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu C-T, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, McCarthy S, Eriksson J, Kwan T, Jhamai M, Trajanoska K, Memari Y, Min J, Huang J, Danecek P, Wilmot B, Li R, Chou W-C, Mokry LE, Moayyeri A, Claussnitzer M, Cheng C-H, Cheung W, Medina-Gómez C, Ge B, Chen S-H, Choi K, Oei L, Fraser J, Kraaij R, Hibbs MA, Gregson CL, Paquette D, Hofman A, Wibom C, Tranah GJ, Marshall M, Gardiner BB, Cremin K, Auer P, Hsu L, Ring S, Tung JY, Thorleifsson G, Enneman AW, van Schoor NM, M. dGLCPG, Nathalie vdV, Melin B, Kemp JP, Christiansen C, Sayers A, Zhou Y, Calderari S, van Rooij J, Carlson C, Peters U, Berlivet S, Dostie J, Uitterlinden AG, Williams SR, Farber C, Grinberg D, LaCroix AZ, Haessler J, Chasman DI, Giulianini F, Rose LM, Ridker PM, Eisman JA, Nguyen TV, Center JR, Nogues X, Garcia-Giralt N, Launer LL, Gudnason V, Mellström D, Vandenput L, Amin N, M. vDC, Karlsson MK, Ljunggren Ö, Svensson O, Hallmans G, Rousseau F, Giroux S, Bussière J, Arp PP, Koromani F, Prince RL, Lewis JR, Langdahl BL, Hermann AP, Jensen J-EB, Kaptoge S, Khaw K-T, Reeve J, Formosa MM, Xuereb-Anastasi A, Åkesson K, McGuigan FE, Garg G, Olmos JM, Zarrabeitia MT, Riancho JA, Ralston SH, Alonso N, Jiang X, Goltzman D, Pastinen T, Grundberg E, Gauguier D, Orwoll ES, Karasik D, Davey-Smith G, Smith AV, Siggeirsdottir K, Harris TB, Zillikens MC, J. vMJB, Thorsteinsdottir U, Maurano MT, Timpson NJ, Soranzo N, Durbin R, Wilson SG, Ntzani EE, Brown MA, Stefansson K, Hinds DA, Spector T, Cupples LA, Ohlsson C, Greenwood CMT, Jackson RD, Rowe DW, Loomis CA, Evans DM, Ackert-Bicknell CL, Joyner AL, Duncan EL, Kiel DP, Rivadeneira F, Richards JB; AOGC Consortium; UK10K Consortium. Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature. October 1, 2015;526(7571):112-117.
2019	Cashen JR. A Comparison of Osteoblast and Osteocyte Expression in Human Bone and Cultured Mesenchymal Stem Cells [Master's thesis]. Boston, MA: Boston University; 2019.
2016	Oei L. Epidemiological, Radiological and Genetic Aspects of Endocrine Bone Diseases [PhD thesis]. Erasmus University Rotterdam; December 14, 2016.
2022	Lu T. Leveraging Complex Disease Polygenic Risk Scores for Improved Risk Prediction and Identification of Rare Genetic Conditions [PhD thesis]. McGill University; April 2022.
2020	Doolittle ML. Dissecting the Genetic Influences on Osteoporosis Reveals Zbtb40* as a Novel Regulator of Osteoblast Function* [PhD thesis]. University of Rochester; 2020.
2013	Rubin KH. The Use of Risk Assessment Tools in the Clinical Management of Osteoporosis [PhD thesis]. University of Southern Denmark (SDU); July 2013.
2014	Nour MA. Impact of Growth Hormone on Adult Bone Quality in Turner Syndrome: A High Resolution Peripheral Quantitative Computed Tomography Study [Master's thesis]. Calgary, AB: University of Calgary; January 2014.
2016	Sebastian A. High-Throughput Analysis of WNT Signaling Pathway in Osteoblasts [PhD thesis]. Merced, CA: Merced, University of California; 2016.