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Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies
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 d...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318312/ https://www.ncbi.nlm.nih.gov/pubmed/30604766 http://dx.doi.org/10.1038/s41467-018-07867-7 |
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author | Morris, Andrew P. Le, Thu H. Wu, Haojia Akbarov, Artur van der Most, Peter J. Hemani, Gibran Smith, George Davey Mahajan, Anubha Gaulton, Kyle J. Nadkarni, Girish N. Valladares-Salgado, Adan Wacher-Rodarte, Niels Mychaleckyj, Josyf C. Dueker, Nicole D. Guo, Xiuqing Hai, Yang Haessler, Jeffrey Kamatani, Yoichiro Stilp, Adrienne M. Zhu, Gu Cook, James P. Ärnlöv, Johan Blanton, Susan H. de Borst, Martin H. Bottinger, Erwin P. Buchanan, Thomas A. Cechova, Sylvia Charchar, Fadi J. Chu, Pei-Lun Damman, Jeffrey Eales, James Gharavi, Ali G. Giedraitis, Vilmantas Heath, Andrew C. Ipp, Eli Kiryluk, Krzysztof Kramer, Holly J. Kubo, Michiaki Larsson, Anders Lindgren, Cecilia M. Lu, Yingchang Madden, Pamela A. F. Montgomery, Grant W. Papanicolaou, George J. Raffel, Leslie J. Sacco, Ralph L. Sanchez, Elena Stark, Holger Sundstrom, Johan Taylor, Kent D. Xiang, Anny H. Zivkovic, Aleksandra Lind, Lars Ingelsson, Erik Martin, Nicholas G. Whitfield, John B. Cai, Jianwen Laurie, Cathy C. Okada, Yukinori Matsuda, Koichi Kooperberg, Charles Chen, Yii-Der Ida Rundek, Tatjana Rich, Stephen S. Loos, Ruth J. F. Parra, Esteban J. Cruz, Miguel Rotter, Jerome I. Snieder, Harold Tomaszewski, Maciej Humphreys, Benjamin D. Franceschini, Nora |
author_facet | Morris, Andrew P. Le, Thu H. Wu, Haojia Akbarov, Artur van der Most, Peter J. Hemani, Gibran Smith, George Davey Mahajan, Anubha Gaulton, Kyle J. Nadkarni, Girish N. Valladares-Salgado, Adan Wacher-Rodarte, Niels Mychaleckyj, Josyf C. Dueker, Nicole D. Guo, Xiuqing Hai, Yang Haessler, Jeffrey Kamatani, Yoichiro Stilp, Adrienne M. Zhu, Gu Cook, James P. Ärnlöv, Johan Blanton, Susan H. de Borst, Martin H. Bottinger, Erwin P. Buchanan, Thomas A. Cechova, Sylvia Charchar, Fadi J. Chu, Pei-Lun Damman, Jeffrey Eales, James Gharavi, Ali G. Giedraitis, Vilmantas Heath, Andrew C. Ipp, Eli Kiryluk, Krzysztof Kramer, Holly J. Kubo, Michiaki Larsson, Anders Lindgren, Cecilia M. Lu, Yingchang Madden, Pamela A. F. Montgomery, Grant W. Papanicolaou, George J. Raffel, Leslie J. Sacco, Ralph L. Sanchez, Elena Stark, Holger Sundstrom, Johan Taylor, Kent D. Xiang, Anny H. Zivkovic, Aleksandra Lind, Lars Ingelsson, Erik Martin, Nicholas G. Whitfield, John B. Cai, Jianwen Laurie, Cathy C. Okada, Yukinori Matsuda, Koichi Kooperberg, Charles Chen, Yii-Der Ida Rundek, Tatjana Rich, Stephen S. Loos, Ruth J. F. Parra, Esteban J. Cruz, Miguel Rotter, Jerome I. Snieder, Harold Tomaszewski, Maciej Humphreys, Benjamin D. Franceschini, Nora |
author_sort | Morris, Andrew P. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6318312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63183122019-01-07 Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies Morris, Andrew P. Le, Thu H. Wu, Haojia Akbarov, Artur van der Most, Peter J. Hemani, Gibran Smith, George Davey Mahajan, Anubha Gaulton, Kyle J. Nadkarni, Girish N. Valladares-Salgado, Adan Wacher-Rodarte, Niels Mychaleckyj, Josyf C. Dueker, Nicole D. Guo, Xiuqing Hai, Yang Haessler, Jeffrey Kamatani, Yoichiro Stilp, Adrienne M. Zhu, Gu Cook, James P. Ärnlöv, Johan Blanton, Susan H. de Borst, Martin H. Bottinger, Erwin P. Buchanan, Thomas A. Cechova, Sylvia Charchar, Fadi J. Chu, Pei-Lun Damman, Jeffrey Eales, James Gharavi, Ali G. Giedraitis, Vilmantas Heath, Andrew C. Ipp, Eli Kiryluk, Krzysztof Kramer, Holly J. Kubo, Michiaki Larsson, Anders Lindgren, Cecilia M. Lu, Yingchang Madden, Pamela A. F. Montgomery, Grant W. Papanicolaou, George J. Raffel, Leslie J. Sacco, Ralph L. Sanchez, Elena Stark, Holger Sundstrom, Johan Taylor, Kent D. Xiang, Anny H. Zivkovic, Aleksandra Lind, Lars Ingelsson, Erik Martin, Nicholas G. Whitfield, John B. Cai, Jianwen Laurie, Cathy C. Okada, Yukinori Matsuda, Koichi Kooperberg, Charles Chen, Yii-Der Ida Rundek, Tatjana Rich, Stephen S. Loos, Ruth J. F. Parra, Esteban J. Cruz, Miguel Rotter, Jerome I. Snieder, Harold Tomaszewski, Maciej Humphreys, Benjamin D. Franceschini, Nora Nat Commun Article 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. Nature Publishing Group UK 2019-01-03 /pmc/articles/PMC6318312/ /pubmed/30604766 http://dx.doi.org/10.1038/s41467-018-07867-7 Text en © The Author(s) 2019 Open Access 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/. |
spellingShingle | Article Morris, Andrew P. Le, Thu H. Wu, Haojia Akbarov, Artur van der Most, Peter J. Hemani, Gibran Smith, George Davey Mahajan, Anubha Gaulton, Kyle J. Nadkarni, Girish N. Valladares-Salgado, Adan Wacher-Rodarte, Niels Mychaleckyj, Josyf C. Dueker, Nicole D. Guo, Xiuqing Hai, Yang Haessler, Jeffrey Kamatani, Yoichiro Stilp, Adrienne M. Zhu, Gu Cook, James P. Ärnlöv, Johan Blanton, Susan H. de Borst, Martin H. Bottinger, Erwin P. Buchanan, Thomas A. Cechova, Sylvia Charchar, Fadi J. Chu, Pei-Lun Damman, Jeffrey Eales, James Gharavi, Ali G. Giedraitis, Vilmantas Heath, Andrew C. Ipp, Eli Kiryluk, Krzysztof Kramer, Holly J. Kubo, Michiaki Larsson, Anders Lindgren, Cecilia M. Lu, Yingchang Madden, Pamela A. F. Montgomery, Grant W. Papanicolaou, George J. Raffel, Leslie J. Sacco, Ralph L. Sanchez, Elena Stark, Holger Sundstrom, Johan Taylor, Kent D. Xiang, Anny H. Zivkovic, Aleksandra Lind, Lars Ingelsson, Erik Martin, Nicholas G. Whitfield, John B. Cai, Jianwen Laurie, Cathy C. Okada, Yukinori Matsuda, Koichi Kooperberg, Charles Chen, Yii-Der Ida Rundek, Tatjana Rich, Stephen S. Loos, Ruth J. F. Parra, Esteban J. Cruz, Miguel Rotter, Jerome I. Snieder, Harold Tomaszewski, Maciej Humphreys, Benjamin D. Franceschini, Nora Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies |
title | Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies |
title_full | Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies |
title_fullStr | Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies |
title_full_unstemmed | Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies |
title_short | Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies |
title_sort | trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318312/ https://www.ncbi.nlm.nih.gov/pubmed/30604766 http://dx.doi.org/10.1038/s41467-018-07867-7 |
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