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Record W4415525502 · doi:10.1126/sciadv.adu1985

Mendelian randomization study implicates inflammaging biomarkers in retinal vasculature, cardiovascular diseases, and longevity

2025· article· en· W4415525502 on OpenAlexaffabout
Ana Villaplana-Velasco, Nicolas Perrot, Yu Huang, Michael Chong, Emanuele Trucco, Muthu Rama Krishnan Mookiah, Jeremy Petch, Hertzel C. Gerstein, Salim Yusuf, Miguel O. Bernabéu, Albert Tenesa, Konrad Rawlik, Guillaume Paré, Alex S. F. Doney, Erola Pairo‐Castineira, Marie Pigeyre

Bibliographic record

VenueScience Advances · 2025
Typearticle
Languageen
FieldMedicine
TopicRetinal Imaging and Analysis
Canadian institutionsImpactUniversity of TorontoHamilton Health SciencesThrombosis and Atherosclerosis Research InstituteMcMaster UniversityPopulation Health Research Institute
FundersFight for Sight UKMedical Research CouncilDiabetes UKBritish Heart Foundation
KeywordsMendelian randomizationBiobankDiseaseConfoundingDiabetes mellitusLongevityEpidemiologyGenome-wide association studyMendelian inheritance

Abstract

fetched live from OpenAlex

With the increasing proportion of elderly individuals, understanding biological mechanisms of aging is critical. Retinal vascular complexity, measured as fractal dimension ( D f ) from fundus photographs, has emerged as a vascular aging indicator. We conducted a genome-wide association study of D f on 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and UK Biobank cohorts. We identified a novel locus near DAAM1 . We found negative genetic correlations between D f and cardiovascular disease, stroke, and inflammation but a positive correlation with life span. By combining the genetic determinants of 1159 circulating proteins from the Prospective Urban and Rural Epidemiological cohort with those of D f using Mendelian randomization, we identified eight causal mediators, including MMP12 and IgG–Fc receptor IIb, which link higher inflammation to lower D f , increased cardiovascular disease risk, and shorter life span. These results extend our understanding of the biological pathways underlying aging processes and inform targets to 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 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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.080
Threshold uncertainty score0.348

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.006
GPT teacher head0.297
Teacher spread0.291 · 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

Citations2
Published2025
Admission routes2
Has abstractyes

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