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Record W4389164112 · doi:10.1101/2023.11.30.23299001

CHIP is associated with cardiovascular disease in the UK Biobank

2023· preprint· en· W4389164112 on OpenAlexaff
Caitlyn Vlasschaert, Giulio Genovese, Yash Pershad, Siddhartha Jaiswal, Pradeep Natarajan, Alexander G. Bick

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldMedicine
TopicAcute Myeloid Leukemia Research
Canadian institutionsQueen's University
Fundersnot available
KeywordsBiobankDiseaseConfoundingCohortBiologyAnticipation (artificial intelligence)GeneticsMedicineInternal medicine

Abstract

fetched live from OpenAlex

Abstract Clonal hematopoiesis (CH) is a form of age-related somatic mosaicism. CH encompasses both clonal events with recognizable leukemic driver mutations, such as CH of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs), as well as clonal states without clear driver mutations. Stacey et al . identify cases of CH from whole genome sequencing (WGS) data in a subset of 130,709 UK Biobank (UKB) participants and in 45,510 individuals from an Icelandic cohort. They report that CH is not associated with cardiovascular disease (CVD) and posit that the multiple prior CH studies did not fully account for smoking-related confounding. We find that the conclusion reached by Stacey et al . is specific to their particular CH definition which groups well-established and clinically meaningful CH subtypes together despite evidence from multiple previous reports that distinct forms of CH have distinct phenotypic consequences. We show that (1) the CHIP/ CVD association in the UK Biobank is not confounded by smoking and (2) CH subtypes which Stacey et al . have lumped together have heterogenous associations with CVD. We suggest that Stacey et al.’s failure to identify an association between CHIP and CVD is perhaps related to methodologic differences compared to prior reports.

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)0.007
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 score0.024
Threshold uncertainty score0.048

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.007
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0060.001

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 head0.052
GPT teacher head0.300
Teacher spread0.247 · 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

Citations6
Published2023
Admission routes1
Has abstractyes

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