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Record W2904863982 · doi:10.1101/499616

Genome-wide association study of diabetic kidney disease highlights biology involved in renal basement membrane collagen

2018· preprint· en· W2904863982 on OpenAlexaff
Rany M. Salem, Jennifer N. Todd, Niina Sandholm, Joanne B. Cole, Wei‐Min Chen, Darrel Andrews, Marcus G. Pezzolesi, Paul McKeigue, Linda T. Hiraki, Chengxiang Qiu, Viji Nair, Chen Di Liao, Jing Cao, Erkka Valo, Suna Önengüt-Gümüşcü, Adam M. Smiles, Stuart J. McGurnaghan, Jani K. Haukka, Valma Harjutsalo, Eoin Brennan, Natalie Van Zuydam, Emma Ahlqvist, Ross Doyle, Tarunveer S. Ahluwalia, Maria Lajer, Maria Hughes, Jihwan Park, Jan Skupień, Athina Spiliopoulou, Andy Liu, Rajasree Menon, Carine M. Boustany‐Kari, Hyun Min Kang, Robert G. Nelson, Ronald Klein, Barbara E.K. Klein, Kristine E. Lee, Xiaoyu Gao, Michael Mauer, Silvia Maeastroni, Maria Luiza Caramori, Ian H. de Boer, Rachel G. Miller, Jingchuan Guo, Andrew P. Boright, David‐Alexandre Trégouët, Beata Gyorgy, Janet K. Snell‐Bergeon, David M. Maahs, Shelley B. Bull, Angelo J. Canty, Lars Stechemesser, Bernhard Paulweber, Raimund Weitgasser, Jeļizaveta Sokolovska, Vita Rovīte, Valdis Pīrāgs, Edita Prakapienė, Lina Radzevičienė, Rasa Verkauskienė, Nicolae Mircea Panduru, Leif Groop, Mark I. McCarthy, Harvest F. Gu, Anna Möllsten, Henrik Falhammar, Kerstin Brismar, Finian Martin, Peter Rossing, Tina Costacou, Gianpaolo Zerbini, Michel Marre, Samy Hadjadj, Amy Jayne McKnight, Carol Forsblom, Gareth J. McKay, Catherine Godson, Alexander P. Maxwell, Matthias Kretzler, Katalin Suszták, Helen M. Colhoun, Andrzej S. Królewski, Andrew D. Paterson, Per‐Henrik Groop, Stephen S. Rich, Joel N. Hirschhorn, José C. Florez

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldMedicine
TopicRenal Diseases and Glomerulopathies
Canadian institutionsLunenfeld-Tanenbaum Research InstituteMcMaster UniversityUniversity of TorontoHospital for Sick Children
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood Institute
KeywordsAlbuminuriaGlomerular basement membraneMissense mutationGenome-wide association studyDiseaseAlport syndromeDiabetic nephropathyGenetic associationPathogenesisGeneticsBiologyKidney diseaseMedicineBioinformaticsMutationGeneKidneySingle-nucleotide polymorphismPathologyInternal medicineGenotypeGlomerulonephritis

Abstract

fetched live from OpenAlex

Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 individuals with type 1 diabetes (T1D) using a spectrum of DKD definitions basedon albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of DKD, including albuminuria and end-stage renal disease. Three other loci are in or near genes with known or suggestive involvement in DKD (BMP7) or renal biology ( COLEC11 and DDR1 ). The 16 DKD-associated loci provide novel insights into the pathogenesis of DKD, identifying potential biological targets for prevention and treatment.

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)0.001
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.013
GPT teacher head0.235
Teacher spread0.222 · 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
GenreEmpirical

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

Citations12
Published2018
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicRenal Diseases and GlomerulopathiesFrench-language works237,207