Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Autoren

Thomas Winkler, Humaira Rasheed, Alexander Teumer, Mathias Gorski, Bryce Rowan, Kira Stanzick, Laurent Thomas, Adrienne Tin, Anselm Hoppmann, Audrey Chu, Bamidele Tayo, Chris Thio, Daniele Cusi, Jin-Fang Chai, Karsten Sieber, Katrin Horn, Man Li, Markus Scholz, Massimiliano Cocca, Matthias Wuttke, van der Most, Peter J, Qiong Yang, Sahar Ghasemi, Teresa Nutile, Yong Li, Giulia Pontali, Felix Günther, Abbas Dehghan, Adolfo Correa, Afshin Parsa, Agnese Feresin, de Vries, Aiko P J, Alan Zonderman, Albert Smith, Albertine Oldehinkel, Alessandro Grandi, Alexander Rosenkranz, Andre Franke, Andrej Teren, Andres Metspalu, Andrew Hicks, Andrew Morris, Anke Tönjes, Anna Morgan, Anna Podgornaia, Annette Peters, Antje Körner, Anubha Mahajan, Archie Campbell, Barry Freedman, Beatrice Spedicati, Belen Ponte, Ben Schöttker, Ben Brumpton, Bernhard Banas, Bernhard Krämer, Bettina Jung, Bjørn Åsvold, Blair Smith, Boting Ning, Penninx, Brenda W J H, Brett Vanderwerff, Bruce Psaty, Candace Kammerer, Carl Langefeld, Caroline Hayward, Cassandra Spracklen, Cassianne Robinson-Cohen, Catharina Hartman, Cecilia Lindgren, Chaolong Wang, Charumathi Sabanayagam, Chew-Kiat Heng, Chiara Lanzani, Chiea-Chuen Khor, Ching-Yu Cheng, Christian Fuchsberger, Christian Gieger, Christian Shaffer, Christina-Alexandra Schulz, Cristen Willer, Daniel Chasman, Daniel Gudbjartsson, Daniela Ruggiero, Daniela Toniolo, Darina Czamara, David Porteous, Dawn Waterworth, Deborah Mascalzoni, Dennis Mook-Kanamori, Dermot Reilly, E. Daw, Edith Hofer, Eric Boerwinkle, Erika Salvi, Erwin Bottinger, E-Shyong Tai, Eulalia Catamo, Federica Rizzi, Feng Guo, Fernando Rivadeneira, Franco Guilianini, Gardar Sveinbjornsson, Georg Ehret, Gerard Waeber, Ginevra Biino, Giorgia Girotto, Giorgio Pistis, Girish Nadkarni, Graciela Delgado, Grant Montgomery, Harold Snieder, Harry Campbell, Harvey White, He Gao, Heather Stringham, Helena Schmidt, Hengtong Li, Hermann Brenner, Hilma Holm, Holgen Kirsten, Holly Kramer, Igor Rudan, Ilja Nolte, Ioanna Tzoulaki, Isleifur Olafsson, Jade Martins, James Cook, James Wilson, Jan Halbritter, Janine Felix, Jasmin Divers, Jaspal Kooner, Jeannette Lee, Jeffrey O'Connell, Jerome Rotter, Jianjun Liu, Jie Xu, Joachim Thiery, Johan Ärnlöv, Johanna Kuusisto, Johanna Jakobsdottir, Johanne Tremblay, John Chambers, John Whitfield, John Gaziano, Jonathan Marten, Josef Coresh, Jost Jonas, Josyf Mychaleckyj, Kaare Christensen, Kai-Uwe Eckardt, Karen Mohlke, Karlhans Endlich, Katalin Dittrich, Kathleen Ryan, Kenneth Rice, Kent Taylor, Kevin Ho, Kjell Nikus, Koichi Matsuda, Konstantin Strauch, Kozeta Miliku, Kristian Hveem, Lars Lind, Lars Wallentin, Laura Yerges-Armstrong, Laura Raffield, Lawrence Phillips, Lenore Launer, Leo-Pekka Lyytikäinen, Leslie Lange, Lorena Citterio, Lucija Klaric, M. Ikram, Marcus Ising, Marcus Kleber, Margherita Francescatto, Maria Concas, Marina Ciullo, Mario Piratsu, Marju Orho-Melander, Markku Laakso, Markus Loeffler, Markus Perola, Martin Borst, Martin Gögele, Martina La Bianca, Mary Lukas, Mary Feitosa, Mary Biggs, Mary Wojczynski, Maryam Kavousi, Masahiro Kanai, Masato Akiyama, Masayuki Yasuda, Matthias Nauck, Melanie Waldenberger, Miao-Li Chee, Miao-Ling Chee, Michael Boehnke, Michael Preuss, Michael Stumvoll, Michael Province, Michele Evans, Michelle O'Donoghue, Michiaki Kubo, Mika Kähönen, Mika Kastarinen, Mike Nalls, Mikko Kuokkanen, Mohsen Ghanbari, Murielle Bochud, Navya Josyula, Nicholas Martin, Nicholas Tan, Nicholette Palmer, Nicola Pirastu, Nicole Schupf, Niek Verweij, Nina Hutri-Kähönen, Nina Mononen, Nisha Bansal, Olivier Devuyst, Olle Melander, Olli Raitakari, Ozren Polasek, Paolo Manunta, Paolo Gasparini, Pashupati Mishra, Patrick Sulem, Patrik Magnusson, Paul Elliott, Paul Ridker, Pavel Hamet, Per Svensson, Peter Joshi, Peter Kovacs, Peter Pramstaller, Peter Rossing, Peter Vollenweider, van der Harst, Pim, Rajkumar Dorajoo, Ralene Sim, Ralph Burkhardt, Ran Tao, Raymond Noordam, Reedik Mägi, Reinhold Schmidt, Renée Mutsert, Rico Rueedi, Rob van Dam, Robert Carroll, Ron Gansevoort, Ruth Loos, Sala Felicita, Sanaz Sedaghat, Sandosh Padmanabhan, Sandra Freitag-Wolf, Sarah Pendergrass, Sarah Graham, Scott Gordon, Shih-Jen Hwang, Shona Kerr, Simona Vaccargiu, Snehal Patil, Stein Hallan, Stephan Bakker, Su-Chi Lim, Susanne Lucae, Suzanne Vogelezang, Sven Bergmann, Tanguy Corre, Tarunveer Ahluwalia, Terho Lehtimäki, Thibaud Boutin, Thomas Meitinger, Tien-Yin Wong, Tobias Bergler, Ton Rabelink, Tõnu Esko, Toomas Haller, Unnur Thorsteinsdottir, Uwe Völker, Valencia Foo, Veikko Salomaa, Veronique Vitart, Vilmantas Giedraitis, Vilmundur Gudnason, Vincent Jaddoe, Wei Huang, Weihua Zhang, Wen Wei, Wieland Kiess, Winfried März, Wolfgang Koenig, Wolfgang Lieb, Xin Gao, Xueling Sim, Ya Wang, Yechiel Friedlander, Yih-Chung Tham, Yoichiro Kamatani, Yukinori Okada, Yuri Milaneschi, Zhi Yu, Klaus Stark, Kari Stefansson, Carsten Böger, Adriana Hung, Florian Kronenberg, Anna Köttgen, Cristian Pattaro, Iris Heid

Jahr

2022

Journal

Communications biology

Pubmed

35697829

Abstract

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n(DM) = 178,691, n(noDM) = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.