Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits (original) (raw)

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Acknowledgements

We thank the subjects of the Icelandic deCODE study, the Danish PERF study and the Australian DOES study for their participation. We also thank the staff at deCODE Genetics core facilities and all our colleagues for their important contribution to this work. The authors would like to thank the NHLBI GO Exome Sequencing Project and its continuing studies, which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923); the WHI Sequencing Project (HL-102924); the Broad GO Sequencing Project (HL-102925); the Seattle GO Sequencing Project (HL-102926); and the Heart GO Sequencing Project (HL-103010). This work was supported in part by the European Commission (HEALTH-F2-2008-201865-GEFOS).

Author information

Authors and Affiliations

  1. deCODE Genetics/Amgen, Reykjavik, 101, Iceland
    Unnur Styrkarsdottir, Gudmar Thorleifsson, Patrick Sulem, Daniel F. Gudbjartsson, Asgeir Sigurdsson, Aslaug Jonasdottir, Adalbjorg Jonasdottir, Asmundur Oddsson, Agnar Helgason, Olafur T. Magnusson, G. Bragi Walters, Michael L. Frigge, Hafdis T. Helgadottir, Hrefna Johannsdottir, Thorunn Rafnar, Augustine Kong, Gisli Masson, Unnur Thorsteinsdottir & Kari Stefansson
  2. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 171 77, Sweden
    Asmundur Oddsson
  3. Department of Biochemistry and Molecular Biology, University of Iceland, Biomedical Center, Faculty of Medicine, 101, Reykjavik, Iceland
    Kristin Bergsteinsdottir, Margret H. Ogmundsdottir & Erikur Steingrimsson
  4. Garvan Institute of Medical Research, Sydney, 2010, Australia
    Jacqueline R. Center, Tuan V. Nguyen & John A. Eisman
  5. St Vincent’s Hospital, Sydney, 2010, Australia
    Jacqueline R. Center & John A. Eisman
  6. University of New South Wales (UNSW), Sydney, 2010, Australia
    Jacqueline R. Center, Tuan V. Nguyen & John A. Eisman
  7. University of Notre Dame Australia (UNDA), Sydney, 2010, Australia
    John A. Eisman
  8. Center for Clinical and Basic Research (CCBR), Ballerup, 2750, Denmark
    Claus Christiansen
  9. Department of Pathology, Landspitali, The National University Hospital of Iceland, Reykjavik, 101, Iceland
    Jon G. Jonasson
  10. Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland
    Jon G. Jonasson, Laufey Tryggvadottir, Thorvaldur Jonsson, Gunnar Sigurdsson, Unnur Thorsteinsdottir & Kari Stefansson
  11. Icelandic Cancer Registry, Reykjavik, 105, Iceland
    Jon G. Jonasson & Laufey Tryggvadottir
  12. Laboratory in Mjodd (RAM), Icelandic Medical Center (Laeknasetrid), Reykjavik, 109, Iceland
    Gudmundur I. Eyjolfsson
  13. Department of Gastroenterology, Landspitali, The National University Hospital of Iceland, Reykjavik, 101, Iceland
    Asgeir Theodors
  14. Department of Surgery, Landspitali, The National University Hospital of Iceland, Reykjavik, 101, Iceland
    Thorvaldur Jonsson
  15. Department of Orthopedic Surgery, Akureyri Hospital, Akureyri, 600, Iceland
    Thorvaldur Ingvarsson
  16. Institution of Health Science, University of Akureyri, Akureyri, 600, Iceland
    Thorvaldur Ingvarsson
  17. Department of Clinical Biochemistry, Landspitali, The National University Hospital of Iceland, Reykjavik, 101, Iceland
    Isleifur Olafsson
  18. Department of Endocrinology and Metabolism, Landspitali, The National University Hospital of Iceland, Reykjavik, 101, Iceland
    Gunnar Sigurdsson

Authors

  1. Unnur Styrkarsdottir
  2. Gudmar Thorleifsson
  3. Patrick Sulem
  4. Daniel F. Gudbjartsson
  5. Asgeir Sigurdsson
  6. Aslaug Jonasdottir
  7. Adalbjorg Jonasdottir
  8. Asmundur Oddsson
  9. Agnar Helgason
  10. Olafur T. Magnusson
  11. G. Bragi Walters
  12. Michael L. Frigge
  13. Hafdis T. Helgadottir
  14. Hrefna Johannsdottir
  15. Kristin Bergsteinsdottir
  16. Margret H. Ogmundsdottir
  17. Jacqueline R. Center
  18. Tuan V. Nguyen
  19. John A. Eisman
  20. Claus Christiansen
  21. Erikur Steingrimsson
  22. Jon G. Jonasson
  23. Laufey Tryggvadottir
  24. Gudmundur I. Eyjolfsson
  25. Asgeir Theodors
  26. Thorvaldur Jonsson
  27. Isleifur Olafsson
  28. Thorunn Rafnar
  29. Augustine Kong
  30. Gunnar Sigurdsson
  31. Gisli Masson
  32. Unnur Thorsteinsdottir
  33. Kari Stefansson

Contributions

The study was designed and results were interpreted by U.S., G.T., D.F.G., P.S., A.K., U.T. and K.S. Sequence data analysis, imputation and association analysis was carried out by G.T., P.S., D.F.G., O.T.M., M.L.F., A.K. and G.M. Subject recruitment, phenotype analysis and biological material collection was organized and carried out by G.B.W., J.R.C., T.V.N., J.A.E., C.C., J.G.J., L.T., G.I.E., A.T., T.J., T.I., I.O., T.R. and G.S. Sequencing and genotyping were supervised by O.T.M. and U.T. Sanger sequencing and Centaurus genotyping was carried out and analysed by H.T.H. and H.J. Expression experiments were carried out and analysed by G.T., A.S., Aslaug J., Adalbjorg J., K.B., M.H.O. and E.S. Multiple alignment and topology analysis of LGR4 was performed by A.O. The age of the LGR4 mutation in the population gene pool was estimated by A.H. The paper was drafted by U.S., G.T., U.T. and K.S. All authors contributed to the final version of the paper.

Corresponding authors

Correspondence toUnnur Thorsteinsdottir or Kari Stefansson.

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Competing interests

U.S., G.T., P.S., A.S., Aslaug J., Adalbjorg J., A.O., D.F.G., A.H., O.T.M., G.B.W., M.L.F., H.T.H., H.J., T.R., A.K., G.M., U.T. and K.S. are employees of deCODE Genetics/Amgen.

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Styrkarsdottir, U., Thorleifsson, G., Sulem, P. et al. Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits.Nature 497, 517–520 (2013). https://doi.org/10.1038/nature12124

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