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000143856 005__ 20240229121829.0
000143856 0247_ $$2doi$$a10.1038/s41588-019-0407-x
000143856 0247_ $$2pmid$$apmid:31152163
000143856 0247_ $$2ISSN$$a1061-4036
000143856 0247_ $$2ISSN$$a1546-1718
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000143856 037__ $$aDKFZ-2019-01418
000143856 041__ $$aeng
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000143856 1001_ $$00000-0003-3420-5082$$aWuttke, Matthias$$b0
000143856 245__ $$aA catalog of genetic loci associated with kidney function from analyses of a million individuals.
000143856 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2019
000143856 3367_ $$2DRIVER$$aarticle
000143856 3367_ $$2DataCite$$aOutput Types/Journal article
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000143856 3367_ $$2BibTeX$$aARTICLE
000143856 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000143856 3367_ $$00$$2EndNote$$aJournal Article
000143856 520__ $$aChronic 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.
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