近日，意大利欧洲生物医学研究所Cristian Pattaro及德国弗莱堡大学医学中心Anna Köttgen等研究人员，开发出从对100万人的分析中得出的与肾功能相关的基因位点目录。相关论文发表在2019年出版的《Nature Genetics》杂志上。

通过对估计肾小球滤过率（eGFR）和独立复制（n = 1,046,070）的全基因组关联研究的跨祖先荟萃分析，课题组人员确定了264个相关基因座（166个新基因）。其中,147人可能相关的肾脏功能的基础上,对替代肾脏功能标记血液尿素氮(n = 416178)。通路富集分析,与肾表型包括motheme模型,支持肾脏的主要靶器官。遗传风险评分降低表皮生长因子受体在452264年与临床诊断CKD独立个体。783,978个欧洲血统个体中与eGFR相关的共定位分析和46个人组织（包括肾小管间质和肾小球肾区室）的基因表达，鉴定了17个在肾脏中差异表达的基因。精细定位了错义司机在11个基因变异和kidney-specific监管变体。这些结果为转化研究提供了全面的分子目标优先级列表。

据介绍，慢性肾病（CKD）是导致多系统并发症的公共卫生负担的原因。

英文原文：

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

Author: Matthias Wuttke, Yong Li, Man Li, Karsten B. Sieber, Mary F. Feitosa, Mathias Gorski, Adrienne Tin, Lihua Wang, Audrey Y. Chu, Anselm Hoppmann, Holger Kirsten, Ayush Giri, Jin-Fang Chai, Gardar Sveinbjornsson, Bamidele O. Tayo, Teresa Nutile, Christian Fuchsberger, Jonathan Marten, Massimiliano Cocca, Sahar Ghasemi, Yizhe Xu, Katrin Horn, Damia Noce, Peter J. van der Most, Sanaz Sedaghat, Zhi Yu, Masato Akiyama, Saima Afaq, Tarunveer S. Ahluwalia, Peter Almgren, Najaf Amin, Johan rnlv, Stephan J. L. Bakker, Nisha Bansal, Daniela Baptista, Sven Bergmann, Mary L. Biggs, Ginevra Biino, Michael Boehnke, Eric Boerwinkle, Mathilde Boissel, Erwin P. Bottinger, Thibaud S. Boutin, Hermann Brenner, Marco Brumat, Ralph Burkhardt, Adam S. Butterworth, Eric Campana, Archie Campbell, Harry Campbell, Mickal Canouil, Robert J. Carroll, Eulalia Catamo, John C. Chambers, Miao-Ling Chee, Miao-Li Chee, Xu Chen, Ching-Yu Cheng, Yurong Cheng, Kaare Christensen, Renata Cifkova, Marina Ciullo, Maria Pina Concas, James P. Cook, Josef Coresh, Tanguy Corre, Cinzia Felicita Sala, Daniele Cusi, John Danesh, E. Warwick Daw, Martin H. de Borst, Alessandro De Grandi, Rene de Mutsert, Aiko P. J. de Vries, Frauke Degenhardt, Graciela Delgado, Ayse Demirkan, Emanuele Di Angelantonio, Katalin Dittrich, Jasmin Divers, Rajkumar Dorajoo, Kai-Uwe Eckardt, Georg Ehret, Paul Elliott, Karlhans Endlich, Michele K. Evans, Janine F. Felix, Valencia Hui Xian Foo, Oscar H. Franco, Andre Franke, Barry I. Freedman, Sandra Freitag-Wolf, Yechiel Friedlander, Philippe Froguel, Ron T. Gansevoort, He Gao, Paolo Gasparini, J. Michael Gaziano, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Franco Giulianini, Martin Ggele, Scott D. Gordon, Daniel F. Gudbjartsson, Vilmundur Gudnason, Toomas Haller, Pavel Hamet, Tamara B. Harris, Catharina A. Hartman, Caroline Hayward, Jacklyn N. Hellwege, Chew-Kiat Heng, Andrew A. Hicks, Edith Hofer, Wei Huang, Nina Hutri-Khnen, Shih-Jen Hwang, M. Arfan Ikram, Olafur S. Indridason, Erik Ingelsson, Marcus Ising, Vincent W. V. Jaddoe, Johanna Jakobsdottir, Jost B. Jonas, Peter K. Joshi, Navya Shilpa Josyula, Bettina Jung, Mika Khnen, Yoichiro Kamatani, Candace M. Kammerer, Masahiro Kanai, Mika Kastarinen, Shona M. Kerr, Chiea-Chuen Khor, Wieland Kiess, Marcus E. Kleber, Wolfgang Koenig, Jaspal S. Kooner, Antje Krner, Peter Kovacs, Aldi T. Kraja, Alena Krajcoviechova, Holly Kramer, Bernhard K. Krmer, Florian Kronenberg, Michiaki Kubo, Brigitte Khnel, Mikko Kuokkanen, Johanna Kuusisto

Issue&Volume:Volume 51 Issue 6, June 2019

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.

DOI: 10.1038/s41588-019-0407-x

Source:https://www.nature.com/articles/s41588-019-0407-x