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New sequence variants associated with bone mineral density


In an extended genome-wide association study of bone mineral density among 6,865 Icelanders and a follow-up in 8,510 subjects of European descent, we identified four new genome-wide significant loci. These are near the SOST gene at 17q21, the MARK3 gene at 14q32, the SP7 gene at 12q13 and the TNFRSF11A (RANK) gene at 18q21. Furthermore, nonsynonymous SNPs in the C17orf53, LRP4, ADAM19 and IBSP genes were suggestively associated with bone density.

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Figure 1: The associated region on 17q21.


  1. Johnell, O. et al. J. Bone Miner. Res. 20, 1185–1194 (2005).

    Article  Google Scholar 

  2. Kanis, J. et al. Osteoporos. Int. 18, 1033 (2007).

    Article  CAS  Google Scholar 

  3. Kanis, J.A. et al. Bone 42, 467–475 (2008).

    Article  CAS  Google Scholar 

  4. Peacock, M., Turner, C.H., Econs, M.J. & Foroud, T. Endocr. Rev. 23, 303–326 (2002).

    Article  CAS  Google Scholar 

  5. Styrkarsdottir, U. et al. N. Engl. J. Med. 358, 2355–2365 (2008).

    Article  CAS  Google Scholar 

  6. Richards, J.B. et al. Lancet 371, 1505–1512 (2008).

    Article  CAS  Google Scholar 

  7. Mizuguchi, T. et al. J. Hum. Genet. 49, 80–86 (2004).

    Article  CAS  Google Scholar 

  8. van Meurs, J.B. et al. J. Am. Med. Assoc. 299, 1277–1290 (2008).

    Article  CAS  Google Scholar 

  9. Uitterlinden, A.G. et al. Am. J. Hum. Genet. 75, 1032 (2004).

    Article  CAS  Google Scholar 

  10. Sims, A.-M. et al. J. Bone Miner. Res. 23, 499–506 (2008).

    Article  CAS  Google Scholar 

  11. Brunkow, M.E. et al. Am. J. Hum. Genet. 68, 577–589 (2001).

    Article  CAS  Google Scholar 

  12. Balemans, W. et al. Hum. Mol. Genet. 10, 537–543 (2001).

    Article  CAS  Google Scholar 

  13. Balemans, W. et al. J. Med. Genet. 39, 91–97 (2002).

    Article  CAS  Google Scholar 

  14. Sigurdsson, G., Halldorsson, B.V., Styrkarsdottir, U., Kristjansson, K. & Stefansson, K. J. Bone Miner. Res. 23, 1584–1590 (2008).

    Article  Google Scholar 

  15. Frazer, K.A. et al. Nature 449, 851–861 (2007).

    Article  CAS  Google Scholar 

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We thank the subjects of the Icelandic deCODE study, the Danish Prospective Epidemiological Risk Factor (PERF) study and the Australian Dubbo Osteoporosis Epidemiology Study (DOES) cohort for their valuable participation. We also thank the staff of the deCODE core facilities and recruitment center for their important contributions to this work.

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U.S., B.V.H., S.G., J.R.G., A.K., U.T. and K.S. designed the study; U.S., S.G., G.B.W., T.I., T.J., J.S., S.S., J.R.C., T.V.N., P.A., J.A.E., C.C. and G.S. collected the data; U.S., B.V.H., D.F.G. and A.K. analyzed the data; U.S., B.V.H., S.G., A.K., U.T. and K.S. wrote the first draft of the paper. All authors contributed to the final version of the paper.

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Correspondence to Unnur Styrkarsdottir or Kari Stefansson.

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Competing interests

The authors U.S., B.V.H., S.G., D.F.G., G.B.W., T.J., J.S., S.S., J.R.G., A.K., U.T. and K.S. are employed by deCODE Genetics and own stock or stock options in the company. J.A.E. reports having received consulting fees, lecture fees or advisory fees from Amgen, deCODE Genetics, Eli-Lilly, GE-Lunar, Merck Sharp & Dohme, Novartis, Organon, Roche-GSK, Sanofi-Aventis, Servier and Wyeth Australia. No other potential conflict of interest relevant to this article was reported.

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Styrkarsdottir, U., Halldorsson, B., Gretarsdottir, S. et al. New sequence variants associated with bone mineral density. Nat Genet 41, 15–17 (2009).

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