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

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    Author
    Wuttke, Matthias
    Köttgen, Anna
    Pattaro, Cristian
    O'Connell, Jeffrey R.
    Ryan, Kathleen A.
    Parsa, Afshin
    Date
    2019-05-31
    Journal
    Nature Genetics
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1038/s41588-019-0407-x
    Abstract
    Chronic 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. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
    Description
    This research has been conducted using the UK Biobank resource under application number 20272. Any methods, additional references, Nature Research reporting summaries, source data, statements of code and data availability and associated accession codes are available at https://doi.org/10.1038/ s41588-019-0407-x.
    Sponsors
    This study is supported by a consulting contract between Data Tecnica International and the National Institute on Aging (NIA), National Institutes of Health (NIH) and consults for Illumina, the Michael J. Fox Foundation and University of California Healthcare.
    Keyword
    Renal Insufficiency, Chronic
    Genetic Loci
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/9566
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41588-019-0407-x
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