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A catalog of genetic loci associated with kidney function from analyses of a million individuals

cam.issuedOnline2019-05-31
cam.orpheus.successThu Jan 30 10:45:39 GMT 2020 - Embargo updated
dc.contributor.authorWuttke, Matthias
dc.contributor.authorLi, Yong
dc.contributor.authorLi, Man
dc.contributor.authorSieber, Karsten B
dc.contributor.authorFeitosa, Mary F
dc.contributor.authorDanesh, John
dc.contributor.authorOuwehand, Willem H
dc.contributor.authorHeid, Iris M
dc.contributor.authorScholz, Markus
dc.contributor.authorTeumer, Alexander
dc.contributor.authorKöttgen, Anna
dc.contributor.authorPattaro, Cristian
dc.contributor.orcidDanesh, John [0000-0003-1158-6791]
dc.contributor.orcidOuwehand, Willem [0000-0002-7744-1790]
dc.date.accessioned2019-05-10T23:30:37Z
dc.date.available2019-05-10T23:30:37Z
dc.date.issued2019-06
dc.description.abstractChronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
dc.identifier.doi10.17863/CAM.39829
dc.identifier.eissn1546-1718
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/292676
dc.language.isoeng
dc.publisherNature Publishing Group
dc.publisher.urlhttp://dx.doi.org/10.1038/s41588-019-0407-x
dc.rightsAll rights reserved
dc.subjectChromosome Mapping
dc.subjectGenetic Association Studies
dc.subjectGenetic Predisposition to Disease
dc.subjectGenome-Wide Association Study
dc.subjectGlomerular Filtration Rate
dc.subjectHumans
dc.subjectInheritance Patterns
dc.subjectKidney Function Tests
dc.subjectPhenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectQuantitative Trait Loci
dc.subjectQuantitative Trait, Heritable
dc.subjectRenal Insufficiency, Chronic
dc.subjectUromodulin
dc.subjectWhite People
dc.titleA catalog of genetic loci associated with kidney function from analyses of a million individuals
dc.typeArticle
dcterms.dateAccepted2019-03-29
prism.endingPage972
prism.publicationNameNature Genetics
prism.startingPage957
prism.volume51
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idBritish Heart Foundation (RG/18/13/33946)
rioxxterms.licenseref.startdate2019-03-29
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1038/s41588-019-0407-x

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