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Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density

Nature Genetics volume 41, pages 926–930 (2009)Cite this article

Abstract

Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the CLDN14 gene that associate with kidney stones (OR = 1.25 and P = 4.0 × 10−12 for rs219780[C]). Approximately 62% of the general population is homozygous for rs219780[C] and is estimated to have 1.64 times greater risk of developing the disease compared to noncarriers. The CLDN14 gene is expressed in the kidney and regulates paracellular permeability at epithelial tight junctions. The same variants were also found to associate with reduced bone mineral density at the hip (P = 0.00039) and spine (P = 0.0077).

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Figure 1: The 21q22 locus.

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Author information

Author notes

  1. Gudmar Thorleifsson and Hilma Holm: These authors contributed equally to this work.

Authors and Affiliations

  1. DeCODE genetics, Sturlugata 8, Reykjavik, 101, Iceland

    Gudmar Thorleifsson, Hilma Holm, G Bragi Walters, Unnur Styrkarsdottir, Daniel F Gudbjartsson, Patrick Sulem, Bjarni V Halldorsson, Thorunn Rafnar, Kristleifur Kristjansson, Augustine Kong, Unnur Thorsteinsdottir & Kari Stefansson

  2. Department of Internal Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA

    Hilma Holm

  3. Department of Pediatrics, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland

    Vidar Edvardsson

  4. Reykjavik University, Reykjavik, Iceland

    Bjarni V Halldorsson

  5. Department of Epidemiology, Biostatistics and Health Technology Assessment, Nijmegen, The Netherlands

    Femmie de Vegt, Martin den Heijer & Lambertus A Kiemeney

  6. Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Frank C H d'Ancona & Lambertus A Kiemeney

  7. Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    Martin den Heijer

  8. Department of Genetics and Molecular Medicine, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland

    Leifur Franzson

  9. Nordic Bioscience A/S, Herlev, Denmark

    Claus Christiansen

  10. Center for Clinical and Basic Research A/S, Ballerup, Denmark

    Peter Alexandersen

  11. Division of Endocrinology and Metabolism, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland

    Gunnar Sigurdsson

  12. Division of Nephrology, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland

    Magnus Bodvarsson, Olafur S Indridason & Runolfur Palsson

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

    Unnur Thorsteinsdottir & Kari Stefansson

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  1. Gudmar Thorleifsson
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Contributions

The study was designed and results interpreted by G.T., H.H., G.B.W., V.E., O.S.I., R.P., M.B., K.K., U.S., T.R., U.T. and K.S. Statistical analysis was carried out by G.T., D.F.G., P.S., B.V.H. and A.K. V.E., O.S.I., R.P., G.S. and L.F. collected the Icelandic data. F.d.V., F.C.H.d'A., M.d.H. and L.A.K. collected the Dutch data. C.C. and P.A. collected the Danish data. Authors H.H., G.T., G.B.W., U.T. and K.S. wrote the first draft of the paper. All authors contributed to the final version.

Corresponding authors

Correspondence to Gudmar Thorleifsson or Kari Stefansson.

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Competing interests

For the authors who are affiliated with deCODE genetics, we declare the following competing financial interests statement: some of the authors employed by deCODE genetics own stock or stock options in the company.

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Thorleifsson, G., Holm, H., Edvardsson, V. et al. Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density. Nat Genet 41, 926–930 (2009). https://doi.org/10.1038/ng.404

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