Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Cristian Pattaro, Alexander Teumer, Mathias Gorski, Audrey Y. Chu, Man Li, Vladan Mijatovic, Maija Garnaas, Adrienne Tin, Rossella Sorice, Yong Li, Daniel Taliun, Matthias Olden, Meredith Foster, Qiong Yang, Ming Huei Chen, Tune H. Pers, Andrew D. Johnson, Yi An Ko, Christian Fuchsberger, Bamidele TayoMichael Nalls, Mary F. Feitosa, Aaron Isaacs, Abbas Dehghan, Pio D'Adamo, Adebowale Adeyemo, Aida Karina Dieffenbach, Alan B. Zonderman, Ilja M. Nolte, Peter J. Van Der Most, Alan F. Wright, Alan R. Shuldiner, Alanna C. Morrison, Albert Hofman, Albert V. Smith, Albert W. Dreisbach, Andre Franke, Andre G. Uitterlinden, Andres Metspalu, Anke Tonjes, Antonio Lupo, Antonietta Robino, Åsa Johansson, Ayse Demirkan, Barbara Kollerits, Barry I. Freedman, Belen Ponte, Ben A. Oostra, Bernhard Paulweber, Bernhard K. Krämer, Braxton D. Mitchell, Brendan M. Buckley, Carmen A. Peralta, Caroline Hayward, Catherine Helmer, Charles N. Rotimi, Christian M. Shaffer, Christian Müller, Cinzia Sala, Cornelia M. Van Duijn, Aude Saint-Pierre, Daniel Ackermann, Daniel Shriner, Daniela Ruggiero, Daniela Toniolo, Yingchang Lu, Daniele Cusi, Darina Czamara, David Ellinghaus, David S. Siscovick, Douglas Ruderfer, Christian Gieger, Harald Grallert, Elena Rochtchina, Elizabeth J. Atkinson, Elizabeth G. Holliday, Eric Boerwinkle, Erika Salvi, Erwin P. Bottinger, Federico Murgia, Fernando Rivadeneira, Florian Ernst, Florian Kronenberg, Frank B. Hu, Gerjan J. Navis, Gary C. Curhan, George B. Ehret, Georg Homuth, Stefan Coassin, Gian Andri Thun, Giorgio Pistis, Giovanni Gambaro, Giovanni Malerba, Grant W. Montgomery, Gudny Eiriksdottir, Gunnar Jacobs, Guo Li, H. Erich Wichmann, Harry Campbell, Helena Schmidt, Henri Wallaschofski, Henry Völzke, Hermann Brenner, Heyo K. Kroemer, Holly Kramer, Honghuang Lin, I. Mateo Leach, Ian Ford, Idris Guessous, Igor Rudan, Inga Prokopenko, Ingrid Borecki, Iris M. Heid, Ivana Kolcic, Ivana Persico, J. Wouter Jukema, James F. Wilson, Janine F. Felix, Jasmin Divers, Jean Charles Lambert, Jeanette M. Stafford, Jean Michel Gaspoz, Jennifer A. Smith, Jessica D. Faul, Jie Jin Wang, Jingzhong Ding, Joel N. Hirschhorn, John Attia, John B. Whitfield, John Chalmers, Jorma Viikari, Josef Coresh, Joshua C. Denny, Juha Karjalainen, Jyotika K. Fernandes, Karlhans Endlich, Katja Butterbach, Keith L. Keene, Kurt Lohman, Laura Portas, Lenore J. Launer, Leo Pekka Lyytikäinen, Loic Yengo, Lude Franke, Luigi Ferrucci, Lynda M. Rose, Lyudmyla Kedenko, Madhumathi Rao, Maksim Struchalin, Marcus E. Kleber, Margherita Cavalieri, Margot Haun, Marilyn C. Cornelis, Marina Ciullo, Mario Pirastu, Mariza De Andrade, Mark A. McEvoy, Mark Woodward, Martin Adam, Massimiliano Cocca, Matthias Nauck, Medea Imboden, Melanie Waldenberger, Menno Pruijm, Marie Metzger, Michael Stumvoll, Michele K. Evans, Michele M. Sale, Mika Kähönen, Mladen Boban, Murielle Bochud, Myriam Rheinberger, Niek Verweij, Nabila Bouatia-Naji, Nicholas G. Martin, Nick Hastie, Nicole Probst-Hensch, Nicole Soranzo, Olivier Devuyst, Olli Raitakari, Omri Gottesman, Oscar H. Franco, Ozren Polasek, Paolo Gasparini, Patricia B. Munroe, Paul M. Ridker, Paul Mitchell, Paul Muntner, Christa Meisinger, Johannes H. Smit, Goncalo R. Abecasis, Linda S. Adair, Myriam Alexander, David Altshuler, Najaf Amin, Dan E. Arking, Pankaj Arora, Yurii Aulchenko, Stephan J.L. Bakker, Stefania Bandinelli, Ines Barroso, Jacques S. Beckmann, John P. Beilby, Richard N. Bergman, Sven Bergmann, Joshua C. Bis, Michael Boehnke, Lori L. Bonnycastle, Stefan R. Bornstein, Michiel L. Bots, Jennifer L. Bragg-Gresham, Stefan Martin Brand, Eva Brand, Peter S. Braund, Morris J. Brown, Paul R. Burton, Juan P. Casas, Mark J. Caulfield, Aravinda Chakravarti, John C. Chambers, Giriraj R. Chandak, Yen Pei C. Chang, Fadi J. Charchar, Nish Chaturvedi, Yoon Shin Cho, Robert Clarke, Francis S. Collins, Rory Collins, John M. Connell, Jackie A. Cooper, Matthew N. Cooper, Richard S. Cooper, Anna Maria Corsi, Marcus Dörr, Santosh Dahgam, John Danesh, George Davey Smith, Ian N.M. Day, Panos Deloukas, Matthew Denniff, Anna F. Dominiczak, Yanbin Dong, Ayo Doumatey, Paul Elliott, Roberto Elosua, Jeanette Erdmann, Susana Eyheramendy, Martin Farrall, Cristiano Fava, Terrence Forrester, F. Gerald R. Fowkes, Ervin R. Fox, Timothy M. Frayling, Pilar Galan, Santhi K. Ganesh, Melissa Garcia, Tom R. Gaunt, Nicole L. Glazer, Min Jin Go, Anuj Goel, Jürgen Grässler, Diederick E. Grobbee, Leif Groop, Simonetta Guarrera, Xiuqing Guo, David Hadley, Anders Hamsten, Bok Ghee Han, Rebecca Hardy, Anna Liisa Hartikainen, Simon Heath, Susan R. Heckbert, Bo Hedblad, Serge Hercberg, Dena Hernandez, Andrew A. Hicks, Gina Hilton, Aroon D. Hingorani, Judith A. Hoffman Bolton, Jemma C. Hopewell, Philip Howard, Steve E. Humphries, Steven C. Hunt, Kristian Hveem, M. Arfan Ikram, Muhammad Islam, Naoharu Iwai, Marjo Riitta Jarvelin, Anne U. Jackson, Tazeen H. Jafar, Charles S. Janipalli, Toby Johnson, Sekar Kathiresan, Kay Tee Khaw, Hyung Lae Kim, Sanjay Kinra, Yoshikuni Kita, Mika Kivimaki, Jaspal S. Kooner, M. J.Kranthi Kumar, Diana Kuh, Smita R. Kulkarni, Meena Kumari, Johanna Kuusisto, Tatiana Kuznetsova, Markku Laakso, Maris Laan, Jaana Laitinen, Edward G. Lakatta, Carl D. Langefeld, Martin G. Larson, Mark Lathrop, Debbie A. Lawlor, Robert W. Lawrence, Jong Young Lee, Nanette R. Lee, Daniel Levy, Yali Li, Will T. Longstreth, Jian'an Luan, Gavin Lucas, Barbara Ludwig, Massimo Mangino, K. Radha Mani, Michael G. Marmot, Francesco U.S. Mattace-Raso, Giuseppe Matullo, Wendy L. McArdle, Colin A. McKenzie, Thomas Meitinger, Olle Melander, Pierre Meneton, James F. Meschia, Tetsuro Miki, Yuri Milaneschi, Karen L. Mohlke, Vincent Mooser, Mario A. Morken, Richard W. Morris, Thomas H. Mosley, Samer Najjar, Narisu Narisu, Christopher Newton-Cheh, Khanh Dung Hoang Nguyen, Peter Nilsson, Fredrik Nyberg, Christopher J. O'Donnell, Toshio Ogihara, Takayoshi Ohkubo, Tomonori Okamura, Rick Twee Hee Ong, Halit Ongen, N. Charlotte Onland-Moret, Paul F. O'Reilly, Elin Org, Marco Orru, Walter Palmas, Jutta Palmen, Lyle J. Palmer, Nicholette D. Palmer, Alex N. Parker, John F. Peden, Leena Peltonen, Markus Perola, Vasyl Pihur, Carl G.P. Platou, Andrew Plump, Dorairajan Prabhakaran, Bruce M. Psaty, Leslie J. Raffel, Dabeeru C. Rao, Asif Rasheed, Fulvio Ricceri, Kenneth M. Rice, Annika Rosengren, Jerome I. Rotter, Megan E. Rudock, Siim Sõber, Tunde Salako, Danish Saleheen, Veikko Salomaa, Nilesh J. Samani, Steven M. Schwartz, Peter E.H. Schwarz, Laura J. Scott, James Scott, Angelo Scuteri, Joban S. Sehmi, Mark Seielstad, Sudha Seshadri, Pankaj Sharma, Sue Shaw-Hawkins, Gang Shi, Nick R.G. Shrine, Eric J.G. Sijbrands, Xueling Sim, Andrew Singleton, Marketa Sjögren, Nicholas L. Smith, Maria Soler Artigas, Tim D. Spector, Jan A. Staessen, Alena Stancakova, Nanette I. Steinle, David P. Strachan, Heather M. Stringham, Yan V. Sun, Amy J. Swift, Yasuharu Tabara, E. Shyong Tai, Philippa J. Talmud, Andrew Taylor, Janos Terzic, Dag S. Thelle, Martin D. Tobin, Maciej Tomaszewski, Vikal Tripathy, Jaakko Tuomilehto, Ioanna Tzoulaki, Manuela Uda, Hirotsugu Ueshima, Cuno S.P.M. Uiterwaal, Satoshi Umemura, Pim Van Der Harst, Yvonne T. Van Der Schouw, Wiek H. Van Gilst, Erkki Vartiainen, Ramachandran S. Vasan, Gudrun Veldre, Germaine C. Verwoert, Margus Viigimaa, D. G. Vinay, Paolo Vineis, Benjamin F. Voight, Peter Vollenweider, Lynne E. Wagenknecht, Louise V. Wain, Xiaoling Wang, Thomas J. Wang, Nicholas J. Wareham, Hugh Watkins, Alan B. Weder, Peter H. Whincup, Kerri L. Wiggins, Jacqueline C.M. Witteman, Andrew Wong, Ying Wu, Chittaranjan S. Yajnik, Jie Yao, J. H. Young, Diana Zelenika, Guangju Zhai, Weihua Zhang, Feng Zhang, Jing Hua Zhao, Haidong Zhu, Xiaofeng Zhu, Paavo Zitting, Ewa Zukowska-Szczechowska, Yukinori Okada, Jer Yuarn Wu, Dongfeng Gu, Fumihiko Takeuchi, Atsushi Takahashi, Shiro Maeda, Tatsuhiko Tsunoda, Peng Chen, Su Chi Lim, Tien Yin Wong, Jianjun Liu, Terri L. Young, Tin Aung, Yik Ying Teo, Young Jin Kim, Daehee Kang, Chien Hsiun Chen, Fuu Jen Tsai, Li Ching Chang, S. J.Cathy Fann, Hao Mei, James E. Hixson, Shufeng Chen, Tomohiro Katsuya, Masato Isono, Eva Albrecht, Kazuhiko Yamamoto, Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani, Norihiro Kato, Jiang He, Yuan Tsong Chen, Toshihiro Tanaka, Muredach P. Reilly, Heribert Schunkert, Themistocles L. Assimes, Alistair Hall, Christian Hengstenberg, Inke R. König, Reijo Laaksonen, Ruth McPherson, John R. Thompson, Unnur Thorsteinsdottir, Andreas Ziegler, Devin Absher, Li Chen, L. Adrienne Cupples, Eran Halperin, Mingyao Li, Kiran Musunuru, Michael Preuss, Arne Schillert, Gudmar Thorleifsson, George A. Wells, Hilma Holm, Robert Roberts, Alexandre F.R. Stewart, Stephen Fortmann, Alan Go, Mark Hlatky, Carlos Iribarren, Joshua Knowles, Richard Myers, Thomas Quertermous, Steven Sidney, Neil Risch, Hua Tang, Stefan Blankenberg, Renate Schnabel, Christoph Sinning, Karl J. Lackner, Laurence Tiret, Viviane Nicaud, Francois Cambien, Christoph Bickel, Hans J. Rupprecht, Claire Perret, Carole Proust, Thomas F. Münzel, Maja Barbalic, Ida Yii Der Chen, Serkalem Demissie-Banjaw, Aaron Folsom, Thomas Lumley, Kristin Marciante, Kent D. Taylor, Kelly Volcik, Solveig Gretarsdottir, Jeffrey R. Gulcher, Augustine Kong, Kari Stefansson, Gudmundur Thorgeirsson, Karl Andersen, Marcus Fischer, Anika Grosshennig, Patrick Linsel-Nitschke, Klaus Stark, Stefan Schreiber, Zouhair Aherrahrou, Petra Bruse, Angela Doering, Norman Klopp, Patrick Diemert, Christina Loley, Anja Medack, Janja Nahrstedt, Annette Peters, Arnika K. Wagner, Christina Willenborg, Bernhard O. Böhm, Harald Dobnig, Tanja B. Grammer, Michael M. Hoffmann, Andreas Meinitzer, Bernhard R. Winkelmann, Stefan Pilz, Wilfried Renner, Hubert Scharnagl, Tatjana Stojakovic, Andreas Tomaschitz, Karl Winkler, Candace Guiducci, Noel Burtt, Stacey B. Gabriel, Sonny Dandona, Olga Jarinova, Liming Qu, Robert Wilensky, William Matthai, Hakon H. Hakonarson, Joe Devaney, Mary Susan Burnett, Augusto D. Pichard, Kenneth M. Kent, Lowell Satler, Joseph M. Lindsay, Ron Waksman, Christopher W. Knouff, Dawn M. Waterworth, Max C. Walker, Stephen E. Epstein, Daniel J. Rader, Christopher P. Nelson, Benjamin J. Wright, Anthony J. Balmforth, Stephen G. Ball, Laura R. Loehr, Wayne D. Rosamond, Emelia Benjamin, Talin Haritunians, David Couper, Joanne Murabito, Ying A. Wang, Bruno H. Stricker, Patricia P. Chang, James T. Willerson, Stephan B. Felix, Norbert Watzinger, Jayashri Aragam, Robert Zweiker, Lars Lind, Richard J. Rodeheffer, Karin Halina Greiser, Jaap W. Deckers, Jan Stritzke, Erik Ingelsson, Iftikhar Kullo, Johannes Haerting, Thorsten Reffelmann, Margaret M. Redfield, Karl Werdan, Gary F. Mitchell, Donna K. Arnett, John S. Gottdiener, Maria Blettner, Nele Friedrich, Peter Kovacs, Philipp S. Wild, Philippe Froguel, Rainer Rettig, Reedik Mägi, Reiner Biffar, Reinhold Schmidt, Rita P.S. Middelberg, Robert J. Carroll, Brenda W. Penninx, Rodney J. Scott, Ronit Katz, Sanaz Sedaghat, Sarah H. Wild, Sharon L.R. Kardia, Sheila Ulivi, Shih Jen Hwang, Stefan Enroth, Stefan Kloiber, Stella Trompet, Benedicte Stengel, Stephen J. Hancock, Stephen T. Turner, Sylvia E. Rosas, Sylvia Stracke, Tamara B. Harris, Tanja Zeller, Tatijana Zemunik, Terho Lehtimäki, Thomas Illig, Thor Aspelund, Tiit Nikopensius, Tonu Esko, Toshiko Tanaka, Ulf Gyllensten, Uwe Völker, Valur Emilsson, Veronique Vitart, Ville Aalto, Vilmundur Gudnason, Vincent Chouraki, Wei Min Chen, Wilmar Igl, Winfried März, Wolfgang Koenig, Wolfgang Lieb, Ruth J.F. Loos, Yongmei Liu, Harold Snieder, Peter P. Pramstaller, Afshin Parsa, Jeffrey R. O'Connell, Katalin Susztak, Pavel Hamet, Johanne Tremblay, Ian H. De Boer, Carsten A. Böger, Wolfram Goessling, Daniel I. Chasman, Anna Köttgen, W. H.Linda Kao, Caroline S. Fox

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Original languageEnglish
Article number10023
JournalNature communications
Volume7
DOIs
Publication statusPublished - 2016 Jan 21

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Pattaro, C., Teumer, A., Gorski, M., Chu, A. Y., Li, M., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Li, Y., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M. H., Pers, T. H., Johnson, A. D., Ko, Y. A., Fuchsberger, C., ... Fox, C. S. (2016). Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nature communications, 7, [10023]. https://doi.org/10.1038/ncomms10023