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

Gudmar Thorleifsson; Hilma Holm; Vidar Edvardsson; G. Bragi Walters; Unnur Styrkarsdottir; Daniel F. Gudbjartsson; Patrick Sulem; Bjarni V. Halldorsson; Femmie De Vegt; Frank C.H. D'Ancona; Martin Den Heijer; Leifur Franzson; Claus Christiansen; Peter Alexandersen; Thorunn Rafnar; Kristleifur Kristjansson; Gunnar Sigurdsson; Lambertus A. Kiemeney; Magnus Bodvarsson; Olafur S. Indridason; Runolfur Palsson; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson

doi:https://doi.org/10.1038/ng.404

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

Gudmar Thorleifsson, Hilma Holm, Vidar Edvardsson, G. Bragi Walters, Unnur Styrkarsdottir, Daniel F. Gudbjartsson, Patrick Sulem, Bjarni V. Halldorsson, Femmie De Vegt, Frank C.H. D'Ancona, Martin Den Heijer, Leifur Franzson, Claus Christiansen, Peter Alexandersen, Thorunn Rafnar, Kristleifur Kristjansson, Gunnar Sigurdsson, Lambertus A. Kiemeney, Magnus Bodvarsson, Olafur S. IndridasonRunolfur Palsson, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson

Internal Medicine (VUmc)

Research output: Contribution to journal › Article › Academic › peer-review

233 Citations (Scopus)

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).

Original language	English
Pages (from-to)	926-930
Number of pages	5
Journal	Nature Genetics
Volume	41
Issue number	8
DOIs	https://doi.org/10.1038/ng.404
Publication status	Published - Aug 2009

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Thorleifsson, G., Holm, H., Edvardsson, V., Walters, G. B., Styrkarsdottir, U., Gudbjartsson, D. F., Sulem, P., Halldorsson, B. V., De Vegt, F., D'Ancona, F. C. H., Den Heijer, M., Franzson, L., Christiansen, C., Alexandersen, P., Rafnar, T., Kristjansson, K., Sigurdsson, G., Kiemeney, L. A., Bodvarsson, M., ... Stefansson, K. (2009). Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density. Nature Genetics, 41(8), 926-930. https://doi.org/10.1038/ng.404

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title = "Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density",

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).",

author = "Gudmar Thorleifsson and Hilma Holm and Vidar Edvardsson and Walters, {G. Bragi} and Unnur Styrkarsdottir and Gudbjartsson, {Daniel F.} and Patrick Sulem and Halldorsson, {Bjarni V.} and {De Vegt}, Femmie and D'Ancona, {Frank C.H.} and {Den Heijer}, Martin and Leifur Franzson and Claus Christiansen and Peter Alexandersen and Thorunn Rafnar and Kristleifur Kristjansson and Gunnar Sigurdsson and Kiemeney, {Lambertus A.} and Magnus Bodvarsson and Indridason, {Olafur S.} and Runolfur Palsson and Augustine Kong and Unnur Thorsteinsdottir and Kari Stefansson",

year = "2009",

month = aug,

doi = "https://doi.org/10.1038/ng.404",

language = "English",

volume = "41",

pages = "926--930",

journal = "Nature Genetics",

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Thorleifsson, G, Holm, H, Edvardsson, V, Walters, GB, Styrkarsdottir, U, Gudbjartsson, DF, Sulem, P, Halldorsson, BV, De Vegt, F, D'Ancona, FCH, Den Heijer, M, Franzson, L, Christiansen, C, Alexandersen, P, Rafnar, T, Kristjansson, K, Sigurdsson, G, Kiemeney, LA, Bodvarsson, M, Indridason, OS, Palsson, R, Kong, A, Thorsteinsdottir, U & Stefansson, K 2009, 'Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density', Nature Genetics, vol. 41, no. 8, pp. 926-930. https://doi.org/10.1038/ng.404

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AU - Thorleifsson, Gudmar

AU - Holm, Hilma

AU - Edvardsson, Vidar

AU - Walters, G. Bragi

AU - Styrkarsdottir, Unnur

AU - Gudbjartsson, Daniel F.

AU - Sulem, Patrick

AU - Halldorsson, Bjarni V.

AU - De Vegt, Femmie

AU - D'Ancona, Frank C.H.

AU - Den Heijer, Martin

AU - Franzson, Leifur

AU - Christiansen, Claus

AU - Alexandersen, Peter

AU - Rafnar, Thorunn

AU - Kristjansson, Kristleifur

AU - Sigurdsson, Gunnar

AU - Kiemeney, Lambertus A.

AU - Bodvarsson, Magnus

AU - Indridason, Olafur S.

AU - Palsson, Runolfur

AU - Kong, Augustine

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

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AB - 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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JO - Nature Genetics

JF - Nature Genetics

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

Abstract

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