, Volume 47, Issue 1, pp 11–21 | Cite as

Genetics of common complex kidney stone disease: insights from genome-wide association studies

  • Runolfur PalssonEmail author
  • Olafur S. Indridason
  • Vidar O. Edvardsson
  • Asmundur Oddsson
Invited Review


Kidney stone disease is a common disorder in Western countries that is associated with significant suffering, morbidity, and cost for the healthcare system. Numerous studies have demonstrated familial aggregation of nephrolithiasis and a twin study estimated the heritability to be 56%. Over the past decade, genome-wide association studies have uncovered several sequence variants that confer increased risk of common complex kidney stone disease. The first reported variants were observed at the CLDN14 locus in the Icelandic population. This finding has since been replicated in other populations. The CLDN14 gene is expressed in tight junctions of the thick ascending limb of the loop of Henle, where the protein is believed to play a role in regulation of calcium transport. More recent studies have uncovered variants at the ALPL, SLC34A1, CASR, and TRPV5 loci, the first two genes playing a role in renal handling of phosphate, while the latter two are involved in calcium homeostasis. Although genetic data have provided insights into the molecular basis of kidney stone disease, much remains to be learned about the contribution of genetic factors to stone formation. Nevertheless, the progress made in recent years indicates that exciting times lie ahead in genetic research on kidney stone disease.


Genealogy Genomics Genotyping Whole-genome sequencing Nephrolithiasis 



Drs. Edvardsson and Palsson are members of the Rare Kidney Stone Consortium which is funded through a collaboration between the NCATS and NIDDK in the US (2U54DK083908). Drs. Edvardsson, Indridason and Palsson have received grants from Landspitali University Hospital Science Fund and the University of Iceland Science Fund.

Compliance with ethical standards

Conflict of interest

Dr. Oddsson is an employee of deCODE genetics. Drs. Edvardsson, Indridason and Palsson are research collaborators of deCODE genetics. The authors declare no other conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors. The article contains no original data. The data presented are solely drawn from previously published work.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Faculty of Medicine, School of Health SciencesUniversity of IcelandReykjavikIceland
  2. 2.Division of Nephrology, Internal Medicine ServicesLandspitali–The National University Hospital of IcelandReykjavikIceland
  3. 3.Children’s Medical CenterLandspitali–The National University Hospital of IcelandReykjavikIceland
  4. 4.Department of StatisticsdeCODE geneticsReykjavikIceland

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