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dc.contributor.authorConnell, J.O
dc.contributor.authorRyan, K.A
dc.contributor.authorParsa, A.
dc.date.accessioned2019-09-18T16:16:22Z
dc.date.available2019-09-18T16:16:22Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85072119437&doi=10.1038%2fs41467-019-11576-0&partnerID=40&md5=2492aa34c0f972c92c823190bd4d0d08
dc.identifier.urihttp://hdl.handle.net/10713/10905
dc.description.abstractIncreased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.en_US
dc.description.urihttps://doi.org/10.1038/s41467-019-11576-0en_US
dc.language.isoen-USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofNature communications
dc.subject.meshAlbuminuriaen_US
dc.subject.meshGenetic Association Studiesen_US
dc.titleGenome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuriaen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-019-11576-0
dc.identifier.pmid31511532


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