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Record W4200002438 · doi:10.1101/2021.12.16.21267446

Decreased retinal vascular complexity is an early biomarker of MI supported by a shared genetic control

2021· preprint· en· W4200002438 on OpenAlexaff
Ana Villaplana-Velasco, Justin Engelmann, Konrad Rawlik, Oriol Canela‐Xandri, Claire Tochel, Frida Lona‐Durazo, Muthu Rama Krishnan Mookiah, Alex S. F. Doney, Esteban J. Parra, Emanuele Trucco, Tom MacGillivray, Kristiina Rannikmäe, Albert Tenesa, Erola Pairo‐Castineira, Miguel O. Bernabéu

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldMedicine
TopicRetinal Imaging and Analysis
Canadian institutionsUniversity of Toronto
FundersBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research CouncilMedical Research CouncilAlan Turing InstituteFondation LeducqEuropean CommissionDiabetes UKBritish Heart Foundation
KeywordsGenome-wide association studyCoronary artery diseaseCADGenetic associationInternal medicineBiobankCardiologyMyocardial infarctionGenotypingMedicineBioinformaticsBiologyGenotypeGeneticsSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

Abstract There is increasing evidence that the complexity of the retinal vasculature (measured as fractal dimension, D f ) might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of D f is poorly understood. We present here a genome-wide association study (GWAS) aimed to elucidate the genetic component of D f and to analyse its relationship with CAD. To this end, we obtained D f from retinal fundus images and genotyping information from ∼38,000 white-British participants in the UK Biobank. We discovered 9 loci associated with D f , previously reported in pigmentation, retinal width and tortuosity, hypertension, and CAD studies. Significant negative genetic correlation estimates endorse the inverse relationship between D f and CAD, and between D f and myocardial infarction (MI), one of CAD fatal outcomes. This strong association motivated us to developing a MI predictive model combining clinical information, D f , a CAD polygenic risk score and using a random forest algorithm. Internal cross validation evidenced a considerable improvement in the area under the curve (AUC) of our predictive model (AUC=0.770) when comparing with an established risk model, SCORE, (AUC=0.719). Our findings shed new light on the genetic basis of D f , unveiling a common control with CAD, and highlights the benefits of its application in individualised MI risk prediction.

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)0.000
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.128
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.038
GPT teacher head0.295
Teacher spread0.257 · 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 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

Citations5
Published2021
Admission routes1
Has abstractyes

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