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Record W4311940464 · doi:10.1101/2022.12.19.22283443

Genome-wide association study of longitudinal urinary albumin excretion in patients with type 1 diabetes

2022· preprint· en· W4311940464 on OpenAlexaff
Anna Hutchinson, Wei‐Min Chen, Suna Önengüt-Gümüşcü, Paul Benitez‐Aguirre, Fergus Cameron, Scott T. Chiesa, Jennifer Couper, Maria E. Craig, Neil Dalton, Denis Daneman, Elizabeth A. Davis, John Deanfield, Kim C. Donaghue, Timothy W. Jones, Farid H. Mahmud, Sally M. Marshall, Andrew Neil, Stephen S. Rich, M. Loredana Marcovecchio, Chris Wallace

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicChronic Kidney Disease and Diabetes
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersNIHR Cambridge Biomedical Research CentreEngineering and Physical Sciences Research CouncilMedical Research CouncilNational Institute for Health and Care ResearchWellcome Trust
KeywordsExcretionAlbuminType 2 diabetesDiabetes mellitusPhenotypeMedicineEndocrinologyInternal medicineGenome-wide association studyBiologyPhysiologyGeneticsGeneGenotypeSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

Abstract Identifying genetic determinants for longitudinal changes in albumin excretion in individuals with type 1 diabetes may help identify those that are predisposed to renal, retinal and cardiovascular complications. Most studies have focussed on genetic predisposition to diabetic kidney disease and used cross-sectional measurements of urinary albumin excretion, but with limited success. Here, we utilise the wealth of longitudinal data and bio-samples collected from cohorts of childhood-onset type 1 diabetes followed over the last 30 years to describe a novel trajectory phenotype quantifying urinary albumin excretion changes during childhood and adolescence. We conducted a genome-wide association study and fine-mapping analysis for albumin excretion in 1584 individuals, finding one signal for cross-sectional albumin excretion close to GALNTL6 (rs150766792), which validated in a previous independent study, and a novel genome-wide significant signal for albumin excretion trajectory in the CDH18 gene region (rs145715205). Our trajectory phenotype quantifies albumin progression and offers a complementary measure to an albumin excretion phenotype based on a single measurement (i.e. most recent data collection) or an average of repeated measurements in longitudinal studies. It can be used to identify genetic or other risk factors which predict better or worse prognosis, thus facilitating the development of new preventive and therapeutic approaches.

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)0.003
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.252
Teacher spread0.238 · 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

Citations0
Published2022
Admission routes1
Has abstractyes

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Same venuemedRxiv→Same topicChronic Kidney Disease and Diabetes→French-language works237,207→