Common and rare variants associated with kidney stones and biochemical traits

Nat Commun. 2015 Aug 14:6:7975. doi: 10.1038/ncomms8975.


Kidney stone disease is a complex disorder with a strong genetic component. We conducted a genome-wide association study of 28.3 million sequence variants detected through whole-genome sequencing of 2,636 Icelanders that were imputed into 5,419 kidney stone cases, including 2,172 cases with a history of recurrent kidney stones, and 279,870 controls. We identify sequence variants associating with kidney stones at ALPL (rs1256328[T], odds ratio (OR)=1.21, P=5.8 × 10(-10)) and a suggestive association at CASR (rs7627468[A], OR=1.16, P=2.0 × 10(-8)). Focusing our analysis on coding sequence variants in 63 genes with preferential kidney expression we identify two rare missense variants SLC34A1 p.Tyr489Cys (OR=2.38, P=2.8 × 10(-5)) and TRPV5 p.Leu530Arg (OR=3.62, P=4.1 × 10(-5)) associating with recurrent kidney stones. We also observe associations of the identified kidney stone variants with biochemical traits in a large population set, indicating potential biological mechanism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genome, Human
  • Genome-Wide Association Study
  • Humans
  • Iceland / epidemiology
  • Kidney Calculi / epidemiology
  • Kidney Calculi / genetics*
  • Odds Ratio
  • Quantitative Trait Loci