Letter abstract
Nature Genetics 41, 926 - 930 (2009)
Published online: 28 June 2009 | doi:10.1038/ng.404
Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density
Gudmar Thorleifsson1,14, Hilma Holm1,2,14, Vidar Edvardsson3, G Bragi Walters1, Unnur Styrkarsdottir1, Daniel F Gudbjartsson1, Patrick Sulem1, Bjarni V Halldorsson1,4, Femmie de Vegt5, Frank C H d'Ancona6, Martin den Heijer5,7, Leifur Franzson8, Claus Christiansen9, Peter Alexandersen10, Thorunn Rafnar1, Kristleifur Kristjansson1, Gunnar Sigurdsson11, Lambertus A Kiemeney5,6, Magnus Bodvarsson12, Olafur S Indridason12, Runolfur Palsson12, Augustine Kong1, Unnur Thorsteinsdottir1,13 & Kari Stefansson1,13
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).
- DeCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
- Department of Internal Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.
- Department of Pediatrics, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland.
- Reykjavik University, Reykjavik, Iceland.
- Department of Epidemiology, Biostatistics and Health Technology Assessment, Nijmegen, The Netherlands.
- Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
- Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
- Department of Genetics and Molecular Medicine, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland.
- Nordic Bioscience A/S, Herlev, Denmark.
- Center for Clinical and Basic Research A/S, Ballerup, Denmark.
- Division of Endocrinology and Metabolism, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland.
- Division of Nephrology, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland.
- University of Iceland, Faculty of Medicine, Reykjavik, Iceland.
- These authors contributed equally to this work.
Correspondence to: Gudmar Thorleifsson1,14 e-mail: gudmar.thorleifsson@decode.is
Correspondence to: Kari Stefansson1,13 e-mail: kstefans@decode.is
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