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

Common and rare variants associated with kidney stones and biochemical traits.

Author information

1
deCODE genetics/Amgen, Inc., Reykjavik 101, Iceland.
2
1] deCODE genetics/Amgen, Inc., Reykjavik 101, Iceland [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik 101, Iceland.
3
1] Children's Medical Center, Landspitali-The National University Hospital of Iceland, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland [3] The Rare Kidney Stone Consortium, Mayo Clinic, Rochester, Minnesota, USA.
4
Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), Reykjavik 109, Iceland.
5
Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, 600, Iceland.
6
Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik 101, Iceland.
7
1] deCODE genetics/Amgen, Inc., Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
8
Division of Nephrology, Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik Iceland.
9
1] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland [2] The Rare Kidney Stone Consortium, Mayo Clinic, Rochester, Minnesota, USA [3] Division of Nephrology, Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik Iceland.

Abstract

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.

PMID:
26272126
PMCID:
PMC4557269
DOI:
10.1038/ncomms8975
[Indexed for MEDLINE]
Free PMC Article

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