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Record W4321781667 · doi:10.1038/s41467-023-36678-8

Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis

2023· article· en· W4321781667 on OpenAlexaff
Younghun Han, Jinyoung Byun, Catherine Zhu, Ryan Sun, Julia Y. Roh, Heather J. Cordell, Hyun‐Sung Lee, Vikram R. Shaw, Sung Wook Kang, Javad Razjouyan, Matthew A. Cooley, Manal M. Hassan, Katherine A. Siminovitch, Trine Folseraas, David Ellinghaus, Annika Bergquist, Simon Rushbrook, André Franke, Tom H. Karlsen, Konstantinos N. Lazaridis, Christoph Schramm, David Shapiro, Elizabeth C. Goode, Katherine A. McGlynn, Lewis R. Roberts, Christopher I. Amos

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldMedicine
TopicLiver Diseases and Immunity
Canadian institutionsLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
FundersNational Center for Research ResourcesCommon FundNational Institute of Environmental Health SciencesNational Human Genome Research InstituteNational Institute of Neurological Disorders and StrokeNational Heart, Lung, and Blood InstituteNational Institute of Mental HealthNIH Office of the DirectorNational Institute on Drug AbuseCholangiocarcinoma FoundationPSC Partners Seeking a CureNational Cancer InstituteNational Institutes of HealthCancer Prevention and Research Institute of Texas
KeywordsPrimary sclerosing cholangitisGenome-wide association studyCandidate geneBiologyLocus (genetics)GeneticsGenetic associationIn silicoDiseaseComputational biologyGeneMedicineSingle-nucleotide polymorphismGenotypeInternal medicine

Abstract

fetched live from OpenAlex

Primary sclerosing cholangitis (PSC) is a rare autoimmune bile duct disease that is strongly associated with immune-mediated disorders. In this study, we implemented multitrait joint analyses to genome-wide association summary statistics of PSC and numerous clinical and epidemiological traits to estimate the genetic contribution of each trait and genetic correlations between traits and to identify new lead PSC risk-associated loci. We identified seven new loci that have not been previously reported and one new independent lead variant in the previously reported locus. Functional annotation and fine-mapping nominated several potential susceptibility genes such as MANBA and IRF5. Network-based in silico drug efficacy screening provided candidate agents for further study of pharmacological effect in PSC.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.129
Threshold uncertainty score0.536

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.059
GPT teacher head0.380
Teacher spread0.321 · 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.

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

Citations32
Published2023
Admission routes1
Has abstractyes

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