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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-01-21

AUTHORS

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 Tayo, Michael 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, ICBP Consortium, 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, RickTwee-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, AGEN Consortium, 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, CARDIOGRAM, 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, CHARGe-Heart Failure Group, 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, ECHOGen Consortium, 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

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. More... »

PAGES

10023

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    N/A

    VOLUME

    7

    Author Affiliations

  • European Academy of Bozen
  • University of Greifswald
  • University Hospital Regensburg
  • Brigham and Women's Hospital
  • Johns Hopkins University
  • University of Verona
  • Institute of Genetics and Biophysics
  • Tufts Medical Center
  • Boston University
  • Boston University School of Medicine
  • Broad Institute
  • University of Pennsylvania
  • Loyola University Medical Center
  • National Institute on Aging
  • Centre for Medical Systems Biology
  • Erasmus University Medical Center
  • IRCCS Materno Infantile Burlo Garofolo
  • National Human Genome Research Institute
  • German Cancer Research Center
  • University Medical Center Groningen
  • University of Edinburgh
  • Baltimore VA Medical Center
  • The University of Texas Health Science Center at Houston
  • University of Iceland
  • University of Mississippi
  • Kiel University
  • University of Tartu
  • Leipzig University
  • Uppsala University
  • Innsbruck Medical University
  • University Hospital of Geneva
  • University Medical Centre Mannheim
  • University College Cork
  • University of California, San Francisco
  • University of Bordeaux
  • Vanderbilt University
  • German Centre for Cardiovascular Research
  • San Raffaele Hospital
  • Établissement Français du Sang
  • Istituto di Genetica Molecolare
  • Icahn School of Medicine at Mount Sinai
  • University of Milan
  • Max Planck Institute of Psychiatry
  • University of Washington
  • Helmholtz Zentrum München
  • German Center for Diabetes Research
  • University of Sydney
  • Mayo Clinic
  • Hunter Medical Research Institute
  • Harvard University
  • University of Basel
  • Catholic University of the Sacred Heart
  • QIMR Berghofer Medical Research Institute
  • Icelandic Heart Association
  • Klinikum der Universität München
  • Medical University of Graz
  • University of Glasgow
  • Emory University
  • Imperial College London
  • University of Split
  • Netherlands Heart Institute
  • Wake Forest Baptist Medical Center
  • Pasteur Institute of Lille
  • University of Michigan–Ann Arbor
  • University of Newcastle Australia
  • Medical University of South Carolina
  • East Carolina University
  • National Institutes of Health
  • University of Tampere
  • Université Lille 2 Droit et Santé
  • Heidelberg University
  • University of Oxford
  • University Hospital of Lausanne
  • University of Paris-Sud
  • University of Virginia
  • Paris Descartes University
  • Wellcome Sanger Institute
  • University of Zurich
  • Queen Mary University of London
  • University of Alabama at Birmingham
  • VU University Medical Center
  • University of North Carolina System
  • University of Cambridge
  • Massachusetts General Hospital
  • Azienda Sanitaria di Firenze
  • University of Lausanne
  • University of Western Australia
  • University of Southern California
  • TU Dresden
  • University Medical Center Utrecht
  • University of Münster
  • University Hospital Münster
  • University of Leicester
  • London School of Hygiene & Tropical Medicine
  • Centre for Cellular and Molecular Biology
  • University of Maryland, Baltimore
  • Federation University
  • Korea National Institute of Health
  • University College London
  • Loyola University Chicago
  • University of Gothenburg
  • University of Bristol
  • Augusta University
  • Pompeu Fabra University
  • University of Lübeck
  • Pontifical Catholic University of Chile
  • Wellcome Centre for Human Genetics
  • Lund University
  • University of the West Indies
  • University of Mississippi Medical Center
  • University of Exeter
  • Paris 13 University
  • Michigan Medicine
  • Skåne University Hospital
  • Human Genetics Foundation
  • Cedars-Sinai Medical Center
  • St George's, University of London
  • Karolinska Institute
  • MRC Unit for Lifelong Health and Ageing
  • University of Oulu
  • Centre National de Génotypage
  • University of Utah
  • Norwegian University of Science and Technology
  • Aga Khan University
  • Shiga University of Medical Science
  • King Edward Memorial Hospital Research Centre
  • KU Leuven
  • Finnish Institute of Occupational Health
  • National Heart Lung and Blood Institute
  • University of San Carlos
  • Case Western Reserve University
  • King's College London
  • University of Turin
  • University of Bonn
  • Centre de Recherche des Cordeliers
  • Mayo Clinic
  • Ehime University
  • University of North Carolina at Chapel Hill
  • GlaxoSmithKline (United States)
  • Osaka University
  • Tohoku University
  • Genome Institute of Singapore
  • University of Cagliari
  • Columbia University
  • Amgen (United States)
  • National Institute for Health and Welfare
  • MSD (United States)
  • Public Health Foundation of India
  • Washington University in St. Louis
  • Center for Non-Communicable Diseases
  • Wake Forest University
  • University of Ibadan
  • National University of Singapore
  • University of Oslo
  • Yokohama City University
  • Tallinn University of Technology
  • Lapland Central Hospital
  • Tokyo Medical and Dental University
  • China Medical University
  • Tsinghua University
  • National Center For Global Health and Medicine
  • RIKEN
  • Centre for Eye Research Australia
  • Duke University Hospital
  • Seoul National University
  • Institute of Biomedical Sciences, Academia Sinica
  • Tulane University
  • University of Tokyo
  • Technical University Munich
  • Stanford University
  • University of Leeds
  • University of Regensburg
  • Tampere University Hospital
  • University of Ottawa
  • International Computer Science Institute
  • deCODE Genetics (Iceland)
  • Kaiser Permanente
  • Johannes Gutenberg University of Mainz
  • Sorbonne University
  • University of Minnesota
  • National University Hospital of Iceland
  • University of Ulm
  • University of Freiburg
  • Children's Hospital of Philadelphia
  • MedStar Washington Hospital Center
  • National Institute of Environmental Health Sciences
  • Texas Medical Center
  • Martin Luther University Halle-Wittenberg
  • University of Maryland Medical Center
  • Leiden University Medical Center
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms10023

    DOI

    http://dx.doi.org/10.1038/ncomms10023

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1043049406

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26831199


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