- Title
- Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies
- Creator
- Morris, Andrew; Le, Thu; Wu, Haojia; Akbarov, Artur; van der Most, Peter; Hemani, Gibran; Smith, George; Mahajan, Anubha; Gaulton, Kyle; Nadkarni, Girish; Valladares-Salgado, Adan; Wacher-Rodarte, Niels; Mychaleckyj, Josyf; Dueker, Nicole; Guo, Xiuqing; Hai, Yang; Haessler, Jeffrey; Kamatani, Yoichiro; Stilp, Adrienne; Zhu, Gu; Cook, James; Arnlov, Johan; Blanton, Susan; de Borst, Martin; Bottinger, Erwin; Buchanan, Thomas; Cechova, Sylvia; Charchar, Fadi; Chu, Pei-Lun; Damman, Jeffrey; Eales, James; Gharavi, Ali; Giedraitis, Vilmantas; Heath, Andrew; Ipp, Eli; Kiryluk, Krzysztof; Kramer, Holly; Kubo, Michiaki; Larsson, Anders; Lindgren, Cecilia; Lu, Yingchang; Madden, Pamela; Montgomery, Grant; Papanicolaou, George; Raffel, Leslie; Sacco, Ralph; Sanchez, Elena; Stark, Holger; Sundstrom, Johan; Taylor, Kent; Xiang, Anny; Zivkovic, Aleksandra; Lind, Lars; Ingelsson, Erik; Martin, Nicholas; Whitfield, John; Cai, Jianwen; Laurie, Cathy; Okada, Yukinori; Matsuda, Koichi; Kooperberg, Charles; Chen, Yii-Der; Rundek, Tatjana; Rich, Stephen; Loos, Ruth; Parra, Esteban; Cruz, Miguel; Rotter, Jerome; Snieder, Harold; Tomaszewski, Maciej; Humphreys, Benjamin; Franceschini, Nora
- Date
- 2019
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/167734
- Identifier
- vital:13698
- Identifier
-
https://doi.org/10.1038/s41467-018-07867-7
- Identifier
- ISBN:2041-1723
- Abstract
- Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.
- Publisher
- Nature Publishing Group
- Relation
- Nature Communications Vol. 10, no. 1 (2019), p. 1-14
- Rights
- http://creativecommons.org/licenses/by/4.0/
- Rights
- Copyright © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
- Rights
- Open Access
- Rights
- This metadata is freely available under a CCO license
- Subject
- MD Multidisciplinary; Diabetic nephropathies; Genome-wide association study; Kidney function
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