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

Wuttke, Matthias; Li, Yong; Li, Man; Sieber, Karsten B; Feitosa, Mary F; Gorski, Mathias; Tin, Adrienne; Wang, Lihua; Chu, Audrey Y; Hoppmann, Anselm; Kirsten, Holger; Giri, Ayush; Chai, Jin-Fang; Sveinbjornsson, Gardar; Tayo, Bamidele O; Nutile, Teresa; Fuchsberger, Christian; Marten, Jonathan; Cocca, Massimiliano; Ghasemi, Sahar; ... (2019). A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nature genetics, 51(6), pp. 957-972. Nature America 10.1038/s41588-019-0407-x

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Franco Duran, Oscar Horacio

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1061-4036

Publisher:

Nature America

Language:

English

Submitter:

Doris Kopp Heim

Date Deposited:

05 Jun 2019 15:40

Last Modified:

12 Jun 2019 16:43

Publisher DOI:

10.1038/s41588-019-0407-x

PubMed ID:

31152163

BORIS DOI:

10.7892/boris.131296

URI:

https://boris.unibe.ch/id/eprint/131296

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