Article | Published:

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

Nature Genetics volume 44, pages 491501 (2012) | Download Citation

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.

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References

  1. 1.

    et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J. Bone Miner. Res. 22, 465–475 (2007).

  2. 2.

    et al. Predictive value of BMD for hip and other fractures. J. Bone Miner. Res. 20, 1185–1194 (2005).

  3. 3.

    et al. 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. 18, 1033–1046 (2007).

  4. 4.

    , , & Genetics of osteoporosis. Endocr. Rev. 23, 303–326 (2002).

  5. 5.

    & Genetics of osteoporosis. Endocr. Rev. 31, 629–662 (2010).

  6. 6.

    & Genomewide association studies and human disease. N. Engl. J. Med. 360, 1759–1768 (2009).

  7. 7.

    Genomewide association studies and assessment of the risk of disease. N. Engl. J. Med. 363, 166–176 (2010).

  8. 8.

    et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371, 1505–1512 (2008).

  9. 9.

    et al. Multiple genetic loci for bone mineral density and fractures. N. Engl. J. Med. 358, 2355–2365 (2008).

  10. 10.

    et al. Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat. Genet. 41, 1199–1206 (2009).

  11. 11.

    et al. New sequence variants associated with bone mineral density. Nat. Genet. 41, 15–17 (2009).

  12. 12.

    et al. An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility loci for osteoporosis-related traits. PLoS Genet. 6, e1000977 (2010).

  13. 13.

    et al. Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies. Am. J. Hum. Genet. 86, 229–239 (2010).

  14. 14.

    et al. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. PLoS Genet. 7, e1001372 (2011).

  15. 15.

    et al. Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann. Intern. Med. 151, 528–537 (2009).

  16. 16.

    et al. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. J. Am. Med. Assoc. 299, 1277–1290 (2008).

  17. 17.

    et al. Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se? Osteoporos. Int. 18, 505–512 (2007).

  18. 18.

    et al. Genetic variation at the low-density lipoprotein receptor–related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 40, 587–596 (2007).

  19. 19.

    et al. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 5, e1000534 (2009).

  20. 20.

    et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832–838 (2010).

  21. 21.

    et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot–containing protein. Am. J. Hum. Genet. 68, 577–589 (2001).

  22. 22.

    et al. Polymorphisms of the low-density lipoprotein receptor–related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study. J. Med. Genet. 43, 798–803 (2006).

  23. 23.

    et al. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 104, 205–215 (2001).

  24. 24.

    , & Genome-wide significant associations for variants with minor allele frequency of 5% or less—an overview: a HuGE review. Am. J. Epidemiol. 172, 869–889 (2010).

  25. 25.

    et al. Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice. J. Clin. Invest. 118, 1858–1866 (2008).

  26. 26.

    , , & Mutant p62P392L stimulation of osteoclast differentiation in Paget's disease of bone. Endocrinology 152, 4180–4189 (2011).

  27. 27.

    et al. Population genomics in a disease targeted primary cell model. Genome Res. 19, 1942–1952 (2009).

  28. 28.

    , , & Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J. Bone Miner. Res. 18, 1766–1774 (2003).

  29. 29.

    & Contribution of gender-specific genetic factors to osteoporosis risk. Ann. Hum. Genet. 72, 696–714 (2008).

  30. 30.

    et al. Genetic determinants of serum testosterone concentrations in men. PLoS Genet. 7, e1002313 (2011).

  31. 31.

    et al. European bone mineral density loci are also associated with BMD in East-Asian populations. PLoS ONE 5, e13217 (2010).

  32. 32.

    et al. Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association. Hum. Mol. Genet. 20, 4082–4092 (2011).

  33. 33.

    , & Emerging anabolic treatments in osteoporosis. Curr. Drug Saf. 6, 62–74 (2011).

  34. 34.

    & Meta-analysis of screening and diagnostic tests. Psychol. Bull. 117, 167–178 (1995).

  35. 35.

    et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. J. Am. Med. Assoc. 282, 1344–1352 (1999).

  36. 36.

    et al. Calcium plus vitamin D supplementation and the risk of fractures. N. Engl. J. Med. 354, 669–683 (2006).

  37. 37.

    et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851–861 (2007).

  38. 38.

    & Imputation-based analysis of association studies: candidate regions and quantitative traits. PLoS Genet. 3, e114 (2007).

  39. 39.

    , , , & A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906–913 (2007).

  40. 40.

    , , & Genotype imputation. Annu. Rev. Genomics Hum. Genet. 10, 387–406 (2009).

  41. 41.

    et al. GRIMP: a web- and grid-based tool for high-speed analysis of large-scale genome-wide association using imputed data. Bioinformatics 25, 2750–2752 (2009).

  42. 42.

    , , & Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30, 97–101 (2002).

  43. 43.

    , & ProbABEL package for genome-wide association analysis of imputed data. BMC Bioinformatics 11, 134 (2010).

  44. 44.

    , & Genomic control, a new approach to genetic-based association studies. Theor. Popul. Biol. 60, 155–166 (2001).

  45. 45.

    , & Validating, augmenting and refining genome-wide association signals. Nat. Rev. Genet. 10, 318–329 (2009).

  46. 46.

    , , & Discovery properties of genome-wide association signals from cumulatively combined data sets. Am. J. Epidemiol. 170, 1197–1206 (2009).

  47. 47.

    et al. Genomic inflation factors under polygenic inheritance. Eur. J. Hum. Genet. 19, 807–812 (2011).

  48. 48.

    , , & Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet. Epidemiol. 32, 381–385 (2008).

  49. 49.

    et al. Eight genes are highly associated with BMD variation in postmenopausal Caucasian women. Bone 46, 604–612 (2010).

  50. 50.

    et al. Global patterns of cis variation in human cells revealed by high-density allelic expression analysis. Nat. Genet. 41, 1216–1222 (2009).

  51. 51.

    et al. Transcriptome genetics using second generation sequencing in a Caucasian population. Nature 464, 773–777 (2010).

  52. 52.

    et al. Population genomics of human gene expression. Nat. Genet. 39, 1217–1224 (2007).

  53. 53.

    et al. Global analysis of the impact of environmental perturbation on cis-regulation of gene expression. PLoS Genet. 7, e1001279 (2011).

  54. 54.

    et al. Genetics of gene expression and its effect on disease. Nature 452, 423–428 (2008).

  55. 55.

    et al. Genetics and beyond—the transcriptome of human monocytes and disease susceptibility. PLoS ONE 5, e10693 (2010).

Download references

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

    • Karol Estrada
    • , Unnur Styrkarsdottir
    • , Evangelos Evangelou
    • , Yi-Hsiang Hsu
    • , Emma L Duncan
    • , Evangelia E Ntzani
    •  & Ling Oei

    These authors contributed equally to this work.

    • 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
    •  & Fernando Rivadeneira

    These authors jointly directed this work.

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. Musculoskeletal Research Programme, Division of Applied Medicine, 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. Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, 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

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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.

Competing interests

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

Corresponding author

Correspondence to Fernando Rivadeneira.

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DOI

https://doi.org/10.1038/ng.2249

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