| Literature DB >> 31152163 |
Matthias Wuttke1,2, Yong Li1, Man Li3, Karsten B Sieber4, Mary F Feitosa5, Mathias Gorski6,7, Adrienne Tin8,9, Lihua Wang5, Audrey Y Chu10, Anselm Hoppmann1, Holger Kirsten11,12, Ayush Giri13,14, Jin-Fang Chai15, Gardar Sveinbjornsson16, Bamidele O Tayo17, Teresa Nutile18, Christian Fuchsberger19, Jonathan Marten20, Massimiliano Cocca21, Sahar Ghasemi22,23, Yizhe Xu3, Katrin Horn11,12, Damia Noce19, Peter J van der Most24, Sanaz Sedaghat25, Zhi Yu8,26, Masato Akiyama27,28, Saima Afaq29,30, Tarunveer S Ahluwalia31, Peter Almgren32, Najaf Amin25, Johan Ärnlöv33,34, Stephan J L Bakker35, Nisha Bansal36,37, Daniela Baptista38, Sven Bergmann39,40,41, Mary L Biggs42,43, Ginevra Biino44, Michael Boehnke45, Eric Boerwinkle46, Mathilde Boissel47, Erwin P Bottinger48,49, Thibaud S Boutin20, Hermann Brenner50,51, Marco Brumat52, Ralph Burkhardt12,53,54, Adam S Butterworth55,56, Eric Campana52, Archie Campbell57, Harry Campbell58, Mickaël Canouil47, Robert J Carroll59, Eulalia Catamo21, John C Chambers29,60,61,62,63, Miao-Ling Chee64, Miao-Li Chee64, Xu Chen65, Ching-Yu Cheng64,66,67, Yurong Cheng1, Kaare Christensen68, Renata Cifkova69,70, Marina Ciullo18,71, Maria Pina Concas21, James P Cook72, Josef Coresh8, Tanguy Corre39,40,73, Cinzia Felicita Sala74, Daniele Cusi75,76, John Danesh77, E Warwick Daw5, Martin H de Borst35, Alessandro De Grandi19, Renée de Mutsert78, Aiko P J de Vries79, Frauke Degenhardt80, Graciela Delgado81, Ayse Demirkan25, Emanuele Di Angelantonio82,83, Katalin Dittrich84,85, Jasmin Divers86, Rajkumar Dorajoo87, Kai-Uwe Eckardt88,89, Georg Ehret38, Paul Elliott90,91,92,93, Karlhans Endlich23,94, Michele K Evans95, Janine F Felix25,96,97, Valencia Hui Xian Foo64, Oscar H Franco25,98, Andre Franke80, Barry I Freedman99, Sandra Freitag-Wolf100, Yechiel Friedlander101, Philippe Froguel47,102, Ron T Gansevoort35, He Gao90, Paolo Gasparini21,52, J Michael Gaziano103, Vilmantas Giedraitis104, Christian Gieger105,106,107, Giorgia Girotto21,52, Franco Giulianini108, Martin Gögele19, Scott D Gordon109, Daniel F Gudbjartsson16, Vilmundur Gudnason110,111, Toomas Haller112, Pavel Hamet113,114, Tamara B Harris115, Catharina A Hartman116, Caroline Hayward20, Jacklyn N Hellwege117,118,119, Chew-Kiat Heng120,121, Andrew A Hicks19, Edith Hofer122,123, Wei Huang124,125, Nina Hutri-Kähönen126,127, Shih-Jen Hwang128,129, M Arfan Ikram25, Olafur S Indridason130, Erik Ingelsson131,132,133,134, Marcus Ising135, Vincent W V Jaddoe25,96,97, Johanna Jakobsdottir136, Jost B Jonas137,138, Peter K Joshi58, Navya Shilpa Josyula139, Bettina Jung6, Mika Kähönen140,141, Yoichiro Kamatani27,142, Candace M Kammerer143, Masahiro Kanai27,144, Mika Kastarinen145, Shona M Kerr20, Chiea-Chuen Khor64,87, Wieland Kiess12,84,85, Marcus E Kleber81, Wolfgang Koenig146,147,148, Jaspal S Kooner61,62,63,149, Antje Körner12,84,85, Peter Kovacs150, Aldi T Kraja5, Alena Krajcoviechova69,70, Holly Kramer17,151, Bernhard K Krämer81, Florian Kronenberg152, Michiaki Kubo153, Brigitte Kühnel105, Mikko Kuokkanen154,155, Johanna Kuusisto145,156, Martina La Bianca21, Markku Laakso145,156, Leslie A Lange157, Carl D Langefeld86, Jeannette Jen-Mai Lee15, Benjamin Lehne29, Terho Lehtimäki158,159, Wolfgang Lieb160, Su-Chi Lim15,161, Lars Lind162, Cecilia M Lindgren163,164, Jun Liu25, Jianjun Liu87,165, Markus Loeffler11,12, Ruth J F Loos48,166, Susanne Lucae135, Mary Ann Lukas167, Leo-Pekka Lyytikäinen158,159, Reedik Mägi112, Patrik K E Magnusson65, Anubha Mahajan168,169, Nicholas G Martin109, Jade Martins170, Winfried März171,172,173, Deborah Mascalzoni19, Koichi Matsuda174, Christa Meisinger175,176, Thomas Meitinger147,177,178, Olle Melander179, Andres Metspalu112, Evgenia K Mikaelsdottir16, Yuri Milaneschi180, Kozeta Miliku25,96,97, Pashupati P Mishra158,159, Karen L Mohlke181, Nina Mononen158,159, Grant W Montgomery182, Dennis O Mook-Kanamori78,183, Josyf C Mychaleckyj184, Girish N Nadkarni48,185, Mike A Nalls186,187, Matthias Nauck23,188, Kjell Nikus189,190, Boting Ning191, Ilja M Nolte24, Raymond Noordam192, Jeffrey O'Connell193, Michelle L O'Donoghue194,195, Isleifur Olafsson196, Albertine J Oldehinkel116, Marju Orho-Melander32, Willem H Ouwehand77, Sandosh Padmanabhan197, Nicholette D Palmer198, Runolfur Palsson111,130, Brenda W J H Penninx180, Thomas Perls199, Markus Perola200, Mario Pirastu201, Nicola Pirastu58, Giorgio Pistis202, Anna I Podgornaia10, Ozren Polasek203,204, Belen Ponte205, David J Porteous57,206, Tanja Poulain12, Peter P Pramstaller19, Michael H Preuss48, Bram P Prins55, Michael A Province5, Ton J Rabelink79,207, Laura M Raffield181, Olli T Raitakari208,209, Dermot F Reilly10, Rainer Rettig210, Myriam Rheinberger6, Kenneth M Rice43, Paul M Ridker108,211, Fernando Rivadeneira25,212, Federica Rizzi213,214, David J Roberts215, Antonietta Robino21, Peter Rossing31, Igor Rudan58, Rico Rueedi39,40, Daniela Ruggiero18,71, Kathleen A Ryan216, Yasaman Saba217, Charumathi Sabanayagam64, Veikko Salomaa200, Erika Salvi213,218, Kai-Uwe Saum50, Helena Schmidt219, Reinhold Schmidt122, Ben Schöttker50,51, Christina-Alexandra Schulz32, Nicole Schupf220,221,222, Christian M Shaffer59, Yuan Shi64, Albert V Smith111, Blair H Smith223, Nicole Soranzo224, Cassandra N Spracklen181, Konstantin Strauch225,226, Heather M Stringham45, Michael Stumvoll227, Per O Svensson228,229, Silke Szymczak100, E-Shyong Tai15,165,230, Salman M Tajuddin95, Nicholas Y Q Tan64, Kent D Taylor231, Andrej Teren12,232, Yih-Chung Tham64, Joachim Thiery12,53, Chris H L Thio24, Hauke Thomsen233, Gudmar Thorleifsson16, Daniela Toniolo74, Anke Tönjes227, Johanne Tremblay113,234, Ioanna Tzoulaki90,235, André G Uitterlinden212, Simona Vaccargiu201, Rob M van Dam15,165, Pim van der Harst236,237,238, Cornelia M van Duijn25, Digna R Velez Edward119,239, Niek Verweij236, Suzanne Vogelezang25,96,97, Uwe Völker23,240, Peter Vollenweider241, Gerard Waeber241, Melanie Waldenberger105,106,147, Lars Wallentin242,243, Ya Xing Wang138, Chaolong Wang87,244, Dawn M Waterworth4, Wen Bin Wei245, Harvey White246, John B Whitfield109, Sarah H Wild247, James F Wilson20,58, Mary K Wojczynski5, Charlene Wong67, Tien-Yin Wong64,67, Liang Xu138, Qiong Yang191, Masayuki Yasuda64,248, Laura M Yerges-Armstrong4, Weihua Zhang61,90, Alan B Zonderman95, Jerome I Rotter231,249,250, Murielle Bochud73, Bruce M Psaty251,252, Veronique Vitart20, James G Wilson253, Abbas Dehghan29,90, Afshin Parsa254,255, Daniel I Chasman108,211, Kevin Ho256,257, Andrew P Morris72,168, Olivier Devuyst258, Shreeram Akilesh37,259, Sarah A Pendergrass260, Xueling Sim15, Carsten A Böger6,261, Yukinori Okada262,263, Todd L Edwards119,118, Harold Snieder24, Kari Stefansson16, Adriana M Hung119,264, Iris M Heid7, Markus Scholz11,12, Alexander Teumer22,23, Anna Köttgen265,266, Cristian Pattaro267.
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.Entities:
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Year: 2019 PMID： 31152163 PMCID： PMC6698888 DOI： 10.1038/s41588-019-0407-x
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330