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Record W3094667387 · doi:10.1016/j.kint.2020.09.030

Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

2020· review· en· W3094667387 on OpenAlexafffund
Mathias Gorski, Bettina Jung, Yong Li, Pamela R. Matías‐García, Matthias Wuttke, Stefan Coassin, Chris H. L. Thio, Marcus E. Kleber, Thomas W. Winkler, Veronika Wanner, Jin Fang Chai, Audrey Y. Chu, Massimiliano Cocca, Mary F. Feitosa, Sahar Ghasemi, Anselm Hoppmann, Katrin Horn, Man Li, Teresa Nutile, Markus Scholz, Karsten B. Sieber, Alexander Teumer, Adrienne Tin, Judy Wang, Bamidele O. Tayo, Tarunveer S. Ahluwalia, Peter Almgren, Stephan J. L. Bakker, Bernhard Banas, Nisha Bansal, Mary L. Biggs, Eric Boerwinkle, Erwin P. Böttinger, Hermann Brenner, Robert J. Carroll, John Chalmers, Miao-Li Chee, Miao-Ling Chee, Ching‐Yu Cheng, Josef Coresh, Martin H. de Borst, Frauke Degenhardt, Kai‐Uwe Eckardt, Karlhans Endlich, André Franke, Sandra Freitag‐Wolf, Piyush Gampawar, Ron T. Gansevoort, Mohsen Ghanbari, Christian Gieger, Pavel Hamet, Kevin Ho, Edith Hofer, Bernd Holleczek, Valencia Hui Xian Foo, Nina Hutri‐Kähönen, Shih‐Jen Hwang, M. Arfan Ikram, Navya Shilpa Josyula, Mika Kähönen, Chiea Chuen Khor, Wolfgang Köenig, Holly Kramer, Bernhard K. Krämer, Brigitte Kühnel, Leslie A. Lange, Terho Lehtimäki, Wolfgang Lieb, Behrooz Z. Alizadeh, H. Marike Boezen, Lude Franke, Gerjan Navis, Marianne G. Rots, Harold Snieder, Morris A. Swertz, Bruce H. R. Wolffenbuttel, Cisca Wijmenga, Gonçalo R. Abecasis, Aris Baras, Michael Cantor, Giovanni Coppola, Aris N. Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan R. Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey Staples, Marcus B. Jones, Lyndon J. Mitnaul, Ruth J. F. Loos, Mary Ann Lukas, Leo‐Pekka Lyytikäinen, Christa Meisinger, Thomas Meitinger, Olle Melander, Yuri Milaneschi, Pashupati P. Mishra, Nina Mononen, Josyf C. Mychaleckyj, Girish N. Nadkarni, Matthias Nauck, Kjell Nikus, Boting Ning, Ilja M. Nolte, Michelle L. O’Donoghue, Marju Orho‐Melander, Sarah A. Pendergrass, Brenda W.J.H. Penninx, Michael Preuß, Bruce M. Psaty, Laura M. Raffield, Olli T. Raitakari, Rainer Rettig, Myriam Rheinberger, Kenneth Rice, Alexander R. Rosenkranz, Peter Rossing, Jerome I. Rotter, Charumathi Sabanayagam, Helena Schmidt, Reinhold Schmidt, Ben Schöttker, Christina‐Alexandra Schulz, Sanaz Sedaghat, Christian M. Shaffer, Konstantin Strauch, Silke Szymczak, Kent D. Taylor, Johanne Tremblay, Layal Chaker, Peter J. van der Most, Niek Verweij, Uwe Völker, Mélanie Waldenberger, Lars Wallentin, Dawn Waterworth, Harvey D. White, James G. Wilson, Tien Yin Wong, Mark Woodward, Qiong Yang, Masayuki Yasuda, Laura M. Yerges-Armstrong, Yan Zhang, Christoph Wanner, Carsten A. Böger, Anna Köttgen, Florian Kronenberg, Cristian Pattaro, Iris M. Heid

Bibliographic record

VenueKidney International · 2020
Typereview
Languageen
FieldMedicine
TopicChronic Kidney Disease and Diabetes
Canadian institutionsUniversité de MontréalMedpharmgene (Canada)
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute on Minority Health and Health DisparitiesNational Center for Research ResourcesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Cancer InstituteNational Center for Advancing Translational SciencesSteno Diabetes Center CopenhagenNational Human Genome Research InstituteNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institute on AgingCanadian Institutes of Health ResearchNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesMedical Research CouncilU.S. National Library of MedicineUniversität RegensburgNovo Nordisk Fonden
KeywordsGenomeRenal functionBiologyFunction (biology)Computational biologyMeta-analysisMedicineGeneticsEvolutionary biologyBioinformaticsInternal medicineGene

Abstract

fetched live from OpenAlex

or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.291
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0040.008
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0170.000

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 head0.105
GPT teacher head0.345
Teacher spread0.240 · 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 teacher head, not a consensus.

Study designMeta-analysis
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

Citations99
Published2020
Admission routes2
Has abstractyes

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