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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 C. Foster, Qiong Yang, Ming‐Huei Chen, Tune H. Pers, Andrew D. Johnson, Yi-An Ko, Christian Fuchsberger, Bamidele O. Tayo, Michael A. 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, André Franke, André G. Uitterlinden, Andres Metspalu, Anke Tönjes, Antonio Lupo, Antonietta Robino, Åsa Johansson, Ayşe Demirkan, Barbara Kollerits, Barry I. Freedman, Belén 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 M. Ruderfer, Christian Gieger, Harald Grallert, Elena Rochtchina, Elizabeth J. Atkinson, Eric Boerwinkle, Erika Salvi, Erwin P. Böttinger, Federico Murgia, Fernando Rivadeneira, Florian Ernst, Florian Kronenberg, Frank B. Hu, Gerjan Navis, Gary C. Curhan, G. Ehret, Georg Homuth, Stefan Coassin, Gian Andri Thun, Giorgio Pistis, Giovanni Gambaro, Giovanni Malerba, Grant W. Montgomery, Guðný Eiríksdóttir, Gunnar Jacobs, Li Guo, H-Erich Wichmann, Harry Campbell, Helena Schmidt, Henri Wallaschofski, Henry Völzke, Hermann Brenner, Heyo K. Kroemer, Holly Kramer, Honghuang Lin, Irene Mateo Leach, Ian Ford, Idris Guessous, Igor Rudan, Inga Prokopenko, Ingrid B. Borecki, Iris M. Heid, Ivana Kolčić, 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, Loïc 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 McEvoy, Mark Woodward, Martin Adam, Massimiliano Cocca, Matthias Nauck, Medea Imboden, Mélanie Waldenberger, Menno Pruijm, Marie Metzger, Michael Stümvoll, Michele K. Evans, Michèle 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 T. Raitakari, Omri Gottesman, Oscar H. Franco, Ozren Polašek, Paolo Gasparini, Patricia B. Munroe, Paul M. Ridker, Paul Mitchell, Paul Muntner, Christa Meisinger, Johannes H. Smit, Gonçalo R. Abecasis, Linda S. Adair, M Alexander, David Altshuler, Najaf Amin, Dan E. Arking, Pankaj Arora, Yurii S. Aulchenko, Stephan J. L. Bakker, Stefania Bandinelli, Inês Barroso, J. Beckmann, John 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, 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 Connell, Jackie A. Cooper, Matthew N. Cooper, A. Corsi, Marcus Dörr, Santosh Dahgam, John Danesh, George Davey Smith, Ian N.M. Day, Panos Deloukas, Matthew Denniff, Anna F. Dominiczak, Yanbin Dong, Ayo P. Doumatey, Paul Elliott, Roberto Elosúa, Jeanette Erdmann, S. Eyheramendy, Martin Farrall, Cristiano Fava, Terrence Forrester, F.G.R. Fowkes, Ervin R. Fox, Timothy M. Frayling, Pilar Galán, Santhi K. Ganesh, Melissa García, 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 Herçberg, Dena Hernández, Andrew A. Hicks, Gina M. Hilton, Aroon D. Hingorani, Judith A. Hoffman Bolton, Jemma C. Hopewell, Philip Howard, Steve E. Humphries, Steven C. Hunt, Kristian Hveem, M. Arfan Ikram, Saiful Islam, Naoharu Iwai, Marjo‐Riitta Järvelin, Anne Jackson, Tazeen H. Jafar, Charles S. Janipalli, Toby Johnson, Sekar Kathiresan, Kay‐Tee Khaw, Hyung‐Lae Kim, Sanjay Kinra, Yoshikuni Kita, Mika Kivimäki, Jaspal S. Kooner, G Anil Kumar, Diana Kuh, Smita 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 Lawrence, Jong‐Young Lee, Sang Lee, Daniel Levy, Yali Li, W. T. Longstreth, Jian’an Luan, Gavin Lucas, Barbara Ludwig, Massimo Mangino, K. Radha Mani, Michael Marmot, Francesco 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 Morris, Thomas H. Mosley, Samer S. Najjar, Narisu Narisu, Christopher Newton‐Cheh, Khanh-Dung H. Nguyen, Peter M. 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 Orrù, Walter Palmas, Jutta Palmen, Lyle J. Palmer, Alex Parker, John F. Peden, Leena Peltonen, Markus Perola, Vasyl Pihur, Carl G. P. Platou, Andrew Plump, Dorairaj Prabhakaran, Bruce M. Psaty, Leslie J. Raffel, D. C. Rao, Asif Rasheed, Fulvio Ricceri, Kenneth Rice, Annika Rosengren, Jerome I. Rotter, Megan E. Rudock, Siim Sõber, Tunde Salako, Danish Saleheen, Veikko Salomaa, Nilesh J. Samani, Steven M. Schwartz, Peter Schwarz, Laura J. Scott, Angelo Scuteri, Joban Sehmi, Mark Seielstad, Sudha Seshadri, Pankaj Sharma, Sue Shaw‐Hawkins, Gang Shi, Nick Shrine, Eric J.G. Sijbrands, Xueling Sim, Andrew B. Singleton, Marketa Sjögren, Nicholas L. Smith, María Soler Artigas, Tim D. Spector, Jan A. Staessen, Alena Stančáková, Nanette Steinle, David P. Strachan, Heather M. Stringham, Yan V. Sun, Amy J. Swift, Yasuharu Tabara, E Shyong Tai, Philippa J. Talmud, Andrew M. Taylor, Janoš Terzić, 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, Péter 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. Hunter Young, Diana Zélénika, Guangju Zhai, Weihua Zhang, Feng Zhang, Wei Zhao, Haidong Zhu, Xiaofeng Zhu, Paavo Zitting, E 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, SJ 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 S. Hall, Christian Hengstenberg, Inke R. König, Reijo Laaksonen, Ruth McPherson, John R. Thompson, Unnur Þorsteinsdóttir, Andreas Ziegler, Devin Absher, Li Chen, L. Adrienne Cupples, Eran Halperin, Mingyao Li, Michael Preuß, Arne Schillert, Guðmar Þorleifsson, George A. Wells, Hilma Hólm, Robert Roberts, Alexandre F.R. Stewart, Stephen P. Fortmann, Alan S. Go, Mark A. Hlatky, Carlos Iribarren, Joshua W. Knowles, Richard H. Myers, Thomas Quertermous, Steven Sidney, Neil Risch, Hua Tang, Stefan Blankenberg, Renate B. Schnabel, Christoph Sinning, Karl J. Lackner, Laurence Tiret, Viviane Nicaud, François Cambien, Christoph Bickel, Hans J. Rupprecht, Claire Perret, Carole Proust, Thomas F. Münzel, Maja Barbalić, Ida Yii-Der Chen, Serkalem Demissie-Banjaw, Aaron R. Folsom, Thomas Lumley, Kristin D. Marciante, Kent D. Taylor, Kelly A. Volcik, Sólveig Grétarsdóttir, Jeffrey R. Gulcher, Augustine Kong, Kāri Stefánsson, Guðmundur Þorgeirsson, 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 Kathleen Wagner, Christina Willenborg, Bernhard Böhm, Harald Dobnig, Tanja B. Grammer, Michael M. Hoffmann, Andreas Meinitzer, Bernhard R. Winkelmann, Stefan Pilz, Wilfried Renner, Hubert Scharnagl, Tatjana Stojaković, Andreas Tomaschitz, Karl Winkler, Candace Guiducci, Noël P. Burtt, Stacey Gabriel, Sonny Dandona, Olga Jarinova, Liming Qu, Robert Wilensky, William Matthai, Håkon Håkonarson, Joe Devaney, Mary Susan Burnett, Augusto D. Pichard, Kenneth M. Kent, Lowell Satler, Joseph Lindsay, Ron Waksman, Christopher W. Knouff, Dawn Waterworth, Max 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 J. Benjamin, Talin Haritunians, David Couper, Joanne M. 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 J. Kullo, Johannes Haerting, Thorsten Reffelmann, Margaret M. Redfield, Karl Werdan, Gary F. Mitchell, Donna K. Arnett, John S. Gottdiener, Maria Blettner, Nele Friedrich, Péter Kovács, Philipp S. Wild, Philippe Froguel, Rainer Rettig, Reedik Mägi, Reiner Biffar, Reinhold Schmidt, Rita P. S. Middelberg, Robert J. Carroll, Brenda W.J.H. Penninx, Rodney J. Scott, Ronit Katz, Sanaz Sedaghat, Sharon L. R. Kardia, Sheila Ulivi, Shih-Jen Hwang, Stefan Enroth, Stefan Kloiber, Stella Trompet, Bénédicte Stengel, Stephen Hancock, Stephen T. Turner, Sylvia E. Rosas, Sylvia Stracke, Tamara B. Harris, Tanja Zeller, Tatijana Zemunik, Terho Lehtimäki, Thomas Illig, Thor Aspelund, Tiit Nikopensius, Tõnu Esko, Toshiko Tanaka, Ulf Gyllensten, Uwe Völker, Valur Emilsson, Véronique Vitart, Ville Aalto, Vilmundur Guðnason, Vincent Chouraki, Wei‐Min Chen, Wilmar Igl, Winfried März, Wolfgang Köenig, Wolfgang Lieb, Ruth J. F. Loos, Ching‐Ti Liu, Harold Snieder, Peter P. Pramstaller, Afshin Parsa, Jeffrey R. O’Connell, Katalin Suszták, 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
Bibliographic record
VenueNature Communications · 2016
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRenal and related cancers
Canadian institutionsCentre Hospitalier de l’Université de MontréalUniversité de MontréalUniversity of Ottawa
FundersNational Institute on Minority Health and Health DisparitiesNational Center for Research ResourcesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNational Institute on AgingNational Human Genome Research InstituteEconomic and Social Research CouncilBritish Heart FoundationNational Cancer InstituteNational Institutes of HealthLundbeckfondenNational Institute for Health and Care ResearchNational Institute of General Medical SciencesMedical Research Council
KeywordsComputational biologyFunction (biology)BiologyBiological pathwayEvolutionary biologyGeneticsBioinformaticsGeneGene expression
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.008
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.027
GPT teacher head0.293
Teacher spread0.266 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designSystematic review
Domainnot available
GenreReview
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations536
Published2016
Admission routes1
Has abstractyes