Common and rare variants associated with kidney stones and biochemical traits.
| dc.contributor.author | Oddsson, Asmundur | |
| dc.contributor.author | Sulem, Patrick | |
| dc.contributor.author | Helgason, Hannes | |
| dc.contributor.author | Edvardsson, Vidar O | |
| dc.contributor.author | Thorleifsson, Gudmar | |
| dc.contributor.author | Sveinbjörnsson, Gardar | |
| dc.contributor.author | Haraldsdottir, Eik | |
| dc.contributor.author | Eyjolfsson, Gudmundur I | |
| dc.contributor.author | Sigurdardottir, Olof | |
| dc.contributor.author | Olafsson, Isleifur | |
| dc.contributor.author | Masson, Gisli | |
| dc.contributor.author | Holm, Hilma | |
| dc.contributor.author | Gudbjartsson, Daniel F | |
| dc.contributor.author | Thorsteinsdottir, Unnur | |
| dc.contributor.author | Indridason, Olafur S | |
| dc.contributor.author | Palsson, Runolfur | |
| dc.contributor.author | Stefansson, Kari | |
| dc.date.accessioned | 2015-10-07T13:46:34Z | en |
| dc.date.available | 2015-10-07T13:46:34Z | en |
| dc.date.issued | 2015 | en |
| dc.date.submitted | 2015 | en |
| dc.identifier.citation | Nat Commun. 2015, 6:7975 | en |
| dc.identifier.issn | 2041-1723 | en |
| dc.identifier.pmid | 26272126 | en |
| dc.identifier.doi | 10.1038/ncomms8975 | en |
| dc.identifier.uri | http://hdl.handle.net/2336/579440 | en |
| dc.description | To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. | en |
| dc.description.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. | |
| dc.description.sponsorship | Rare Kidney Stone Consortium 5U54DK083908-07 National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) Rare Kidney Stone Consortium | en |
| dc.language.iso | en | en |
| dc.publisher | Nature Publishing Group | en |
| dc.relation.url | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557269/ | en |
| dc.rights | Archived with thanks to Nature communications | en |
| dc.subject | Nýrnasteinar | en |
| dc.subject | Arfgengi | en |
| dc.subject.mesh | Kidney Calculi/genetics | en |
| dc.subject.mesh | Genome-Wide Association Study | en |
| dc.subject.mesh | Iceland | en |
| dc.title | Common and rare variants associated with kidney stones and biochemical traits. | en |
| dc.type | Article | en |
| dc.contributor.department | Addresses: [ 1 ] DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland [Show the Organization-Enhanced name(s)] [ 2 ] Univ Iceland, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland [ 3 ] Landspitali, Childrens Med Ctr, IS-101 Reykjavik, Iceland [Show the Organization-Enhanced name(s)] [ 4 ] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland [Show the Organization-Enhanced name(s)] [ 5 ] Mayo Clin, Rare Kidney Stone Consortium, Rochester, MN USA [ 6 ] Iceland Med Ctr Laeknasetrid, Lab Mjodd RAM, IS-109 Reykjavik, Iceland [ 7 ] Akureyri Hosp, Dept Clin Biochem, IS-600 Akureyri, Iceland [Hide the Organization-Enhanced name(s)] [ 8 ] Landspitali Univ Hosp, Dept Clin Biochem, IS-101 Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital [ 9 ] Landspitali, Div Nephrol, Internal Med Serv, Reykjavik, Iceland | en |
| dc.identifier.journal | Nature communications | en |
| dc.rights.access | Open Access | en |
| refterms.dateFOA | 2018-09-12T15:39:43Z | |
| html.description.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. |
