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Record W4376868368 · doi:10.1101/2023.05.16.23290063

Insights into human health from phenome- and genome-wide analyses of UK Biobank retinal optical coherence tomography phenotypes

2023· preprint· en· W4376868368 on OpenAlexaff
Seyedeh M. Zekavat, Saman Doroodgar Jorshery, Yusrah Shweikh, Katrin Horn, Franziska G. Rauscher, Sayuri Sekimitsu, Satoshi Kayoma, Yixuan Ye, Vineet K. Raghu, Hongyu Zhao, Marzyeh Ghassemi, Tobias Elze, Ayellet V. Segrè, Janey L. Wiggs, Markus Scholz, Lucian Del Priore, Jay Wang, Pradeep Natarajan, Nazlee Zebardast

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldMedicine
TopicRetinal Imaging and Analysis
Canadian institutionsVector InstituteUniversity of Toronto
Fundersnot available
KeywordsPhenomeRetinalBiobankGenome-wide association studyRetinaOphthalmologyNerve fiber layerMedicineBiologyPhenotypeGeneticsNeuroscienceGenotypeSingle-nucleotide polymorphismGene

Abstract

fetched live from OpenAlex

The human retina is a complex multi-layered tissue which offers a unique window into systemic health and disease. Optical coherence tomography (OCT) is widely used in eye care and allows the non-invasive, rapid capture of retinal measurements in exquisite detail. We conducted genome- and phenome-wide analyses of retinal layer thicknesses using macular OCT images from 44,823 UK Biobank participants. We performed phenome-wide association analyses, associating retinal thicknesses with 1,866 incident ICD-based conditions (median 10-year follow-up) and 88 quantitative traits and blood biomarkers. We performed genome-wide association analyses, identifying inherited genetic markers which influence the retina, and replicated our associations among 6,313 individuals from the LIFE-Adult Study. And lastly, we performed comparative association of phenome- and genome- wide associations to identify putative causal links between systemic conditions, retinal layer thicknesses, and ocular disease. Independent associations with incident mortality were detected for photoreceptor thinning and ganglion cell complex thinning. Significant phenotypic associations were detected between retinal layer thinning and ocular, neuropsychiatric, cardiometabolic and pulmonary conditions. Genome-wide association of retinal layer thicknesses yielded 259 loci. Consistency between epidemiologic and genetic associations suggested putative causal links between thinning of the retinal nerve fiber layer with glaucoma, photoreceptor segment with AMD, as well as poor cardiometabolic and pulmonary function with PS thinning, among other findings. In conclusion, retinal layer thinning predicts risk of future ocular and systemic disease. Furthermore, systemic cardio-metabolic-pulmonary conditions promote retinal thinning. Retinal imaging biomarkers, integrated into electronic health records, may inform risk prediction and potential therapeutic strategies.

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)0.002
metaresearch head score (Gemma)0.006
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 score0.015
Threshold uncertainty score0.029

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.006
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.060
GPT teacher head0.354
Teacher spread0.293 · 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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