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dc.contributor.authorOddsson, Asmundur
dc.contributor.authorSulem, Patrick
dc.contributor.authorHelgason, Hannes
dc.contributor.authorEdvardsson, Vidar O
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorSveinbjörnsson, Gardar
dc.contributor.authorHaraldsdottir, Eik
dc.contributor.authorEyjolfsson, Gudmundur I
dc.contributor.authorSigurdardottir, Olof
dc.contributor.authorOlafsson, Isleifur
dc.contributor.authorMasson, Gisli
dc.contributor.authorHolm, Hilma
dc.contributor.authorGudbjartsson, Daniel F
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorIndridason, Olafur S
dc.contributor.authorPalsson, Runolfur
dc.contributor.authorStefansson, Kari
dc.date.accessioned2015-10-07T13:46:34Zen
dc.date.available2015-10-07T13:46:34Zen
dc.date.issued2015en
dc.date.submitted2015en
dc.identifier.citationNat Commun. 2015, 6:7975en
dc.identifier.issn2041-1723en
dc.identifier.pmid26272126en
dc.identifier.doi10.1038/ncomms8975en
dc.identifier.urihttp://hdl.handle.net/2336/579440en
dc.descriptionTo 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.abstractKidney 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.sponsorshipRare Kidney Stone Consortium 5U54DK083908-07 National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) Rare Kidney Stone Consortiumen
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557269/en
dc.rightsArchived with thanks to Nature communicationsen
dc.subjectNýrnasteinaren
dc.subjectArfgengien
dc.subject.meshKidney Calculi/geneticsen
dc.subject.meshGenome-Wide Association Studyen
dc.subject.meshIcelanden
dc.titleCommon and rare variants associated with kidney stones and biochemical traits.en
dc.typeArticleen
dc.contributor.departmentAddresses: [ 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, Icelanden
dc.identifier.journalNature communicationsen
dc.rights.accessOpen Accessen
refterms.dateFOA2018-09-12T15:39:43Z
html.description.abstractKidney 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.


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