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


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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NCBI Reference Sequence


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Author information




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).

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