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Record W2947278243 · doi:10.1038/s41588-019-0407-x

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

2019· review· en· W2947278243 on OpenAlexaff
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, Garðar Sveinbjörnsson, 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. Böttinger, Thibaud 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 Cífková, Marina Ciullo, Maria Pina Concas, James P. Cook, Josef Coresh, Tanguy Corre, Cinzia 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, Ayşe 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, André 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, Daníel F. Guðbjartsson, Vilmundur Guðnason, 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, Ólafur S. Indridason, Erik Ingelsson, Marcus Ising, Vincent W. V. Jaddoe, Jóhanna Jakobsdóttir, 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 Köenig, Jaspal S. Kooner, Antje Körner, Péter Kovács, Aldi T. Kraja, Alena Krajčoviechová, 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, S. M. L. 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 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 R. O’Connell, Michelle L. O’Donoghue, Ísleifur Ólafsson, Albertine J. Oldehinkel, Marju Orho‐Melander, Willem H. Ouwehand, Sandosh Padmanabhan, Runólfur Pálsson, Brenda W.J.H. Penninx, Thomas T. Perls, Markus Perola, Mario Pirastu, Nicola Pirastu, Giorgio Pistis, Anna Podgornaia, Ozren Polašek, Belén Ponte, David J. Porteous, Tanja Poulain, Peter P. Pramstaller, Michael Preuß, Bram P. Prins, Michael A. Province, Ton J. Rabelink, Laura M. Raffield, Olli T. Raitakari, Dermot F. Reilly, Rainer Rettig, Myriam Rheinberger, Kenneth 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 Stümvoll, Per Svensson, Silke Szymczak, E Shyong Tai, Salman M. Tajuddin, Nicholas Tan, Kent D. Taylor, Andrej Teren, Yih Chung Tham, Joachim Thiery, Chris H. L. Thio, Hauke Thomsen, Guðmar Þorleifsson, 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, D Edward, Niek Verweij, Suzanne Vogelezang, Uwe Völker, Péter Vollenweider, Gérard Waeber, Mélanie Waldenberger, Lars Wallentin, Ya Xing Wang, Chaolong Wang, Dawn Waterworth, Wen Bin Wei, Harvey D. 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, Véronique 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, Kāri Stefánsson, Adriana M. Hung, Iris M. Heid, Markus Scholz, Alexander Teumer, Anna Köttgen, Cristian Pattaro

Bibliographic record

VenueNature Genetics · 2019
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMedpharmgene (Canada)
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Heart, Lung, and Blood InstituteNational Institutes of HealthNovo Nordisk FondenEisaiWellcome TrustSirtex MedicalAlbert-Ludwigs-Universität FreiburgBritish Heart FoundationNovo NordiskNational Institute on AgingCSL BehringNational Institute for Health and Care ResearchAgence Nationale de la RechercheSteno Diabetes Center CopenhagenEli Lilly and CompanyAstraZenecaNestecYale UniversityAmerican RegentNational Institute of Diabetes and Digestive and Kidney DiseasesSanofiMedical Research CouncilPfizerBiogenGlaxoSmithKlineUniversity of Warwick
KeywordsBiologyGeneticsEvolutionary biologyFunction (biology)Computational biology

Abstract

fetched live from OpenAlex

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.

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 imitation

Not 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)0.002
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.004
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0040.004
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0030.001

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 head0.036
GPT teacher head0.334
Teacher spread0.298 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine 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 designObservational
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".

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Citations921
Published2019
Admission routes1
Has abstractno

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