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

Authors:
Mr. Hauke Thomsen, Dr.
Mr. Hauke Thomsen, Dr.
GeneWerk GmbH
Senior Bioinformatician
Bioinformatics, Biostatistics, Genetics
Heidelberg, Baden-Württemberg/Germany | Germany
Navya Josyula
Navya Josyula
Biomedical and Translational Informatics Institute
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 Ärnlöv 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 Mickaël 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 Renée 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 Gögele 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-Kähönen 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 Kähönen 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 Körner Peter Kovacs Aldi T Kraja Alena Krajcoviechova Holly Kramer Bernhard K Krämer Florian Kronenberg Michiaki Kubo Brigitte Kühnel Mikko Kuokkanen Johanna Kuusisto Martina La Bianca Markku Laakso Leslie A Lange Carl D Langefeld Jeannette Jen-Mai Lee Benjamin Lehne Terho Lehtimäki Wolfgang Lieb Su-Chi Lim Lars Lind Cecilia M Lindgren Jun Liu Jianjun Liu Markus Loeffler Ruth J F Loos Susanne Lucae Mary Ann Lukas Leo-Pekka Lyytikäinen Reedik Mägi Patrik K E Magnusson Anubha Mahajan Nicholas G Martin Jade Martins Winfried März Deborah Mascalzoni Koichi Matsuda Christa Meisinger Thomas Meitinger Olle Melander Andres Metspalu Evgenia K Mikaelsdottir Yuri Milaneschi Kozeta Miliku Pashupati P Mishra Karen L Mohlke Nina Mononen Grant W Montgomery Dennis O Mook-Kanamori Josyf C Mychaleckyj Girish N Nadkarni Mike A Nalls Matthias Nauck Kjell Nikus Boting Ning Ilja M Nolte Raymond Noordam Jeffrey O'Connell Michelle L O'Donoghue Isleifur Olafsson Albertine J Oldehinkel Marju Orho-Melander Willem H Ouwehand Sandosh Padmanabhan Nicholette D Palmer Runolfur Palsson Brenda W J H Penninx Thomas Perls Markus Perola Mario Pirastu Nicola Pirastu Giorgio Pistis Anna I Podgornaia Ozren Polasek Belen Ponte David J Porteous Tanja Poulain Peter P Pramstaller Michael H Preuss Bram P Prins Michael A Province Ton J Rabelink Laura M Raffield Olli T Raitakari Dermot F Reilly Rainer Rettig Myriam Rheinberger Kenneth M Rice Paul M Ridker Fernando Rivadeneira Federica Rizzi David J Roberts Antonietta Robino Peter Rossing Igor Rudan Rico Rueedi Daniela Ruggiero Kathleen A Ryan Yasaman Saba Charumathi Sabanayagam Veikko Salomaa Erika Salvi Kai-Uwe Saum Helena Schmidt Reinhold Schmidt Ben Schöttker Christina-Alexandra Schulz Nicole Schupf Christian M Shaffer Yuan Shi Albert V Smith Blair H Smith Nicole Soranzo Cassandra N Spracklen Konstantin Strauch Heather M Stringham Michael Stumvoll Per O Svensson Silke Szymczak E-Shyong Tai Salman M Tajuddin Nicholas Y Q Tan Kent D Taylor Andrej Teren Yih-Chung Tham Joachim Thiery Chris H L Thio Gudmar Thorleifsson Daniela Toniolo Anke Tönjes Johanne Tremblay Ioanna Tzoulaki André G Uitterlinden Simona Vaccargiu Rob M van Dam Pim van der Harst Cornelia M van Duijn Digna R Velez Edward Niek Verweij Suzanne Vogelezang Uwe Völker Peter Vollenweider Gerard Waeber Melanie Waldenberger Lars Wallentin Ya Xing Wang Chaolong Wang Dawn M Waterworth Wen Bin Wei Harvey White John B Whitfield Sarah H Wild James F Wilson Mary K Wojczynski Charlene Wong Tien-Yin Wong Liang Xu Qiong Yang Masayuki Yasuda Laura M Yerges-Armstrong Weihua Zhang Alan B Zonderman Jerome I Rotter Murielle Bochud Bruce M Psaty Veronique Vitart James G Wilson Abbas Dehghan Afshin Parsa Daniel I Chasman Kevin Ho Andrew P Morris Olivier Devuyst Shreeram Akilesh Sarah A Pendergrass Xueling Sim Carsten A Böger Yukinori Okada Todd L Edwards Harold Snieder Kari Stefansson Adriana M Hung Iris M Heid Markus Scholz Alexander Teumer Anna Köttgen Cristian Pattaro

Nat Genet 2019 06 31;51(6):957-972. Epub 2019 May 31.

Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.

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.

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http://dx.doi.org/10.1038/s41588-019-0407-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698888PMC
June 2019
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