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Record W4412627988 · doi:10.1101/2025.07.20.665796

A comparative GWAS of eye colour in light and dark eye genetic backgrounds defined by <i>HERC2</i> rs12913832 polymorphism

2025· preprint· en· W4412627988 on OpenAlexafffundabout
Cristina Abbatangelo, Frida Lona‐Durazo, Melissa Edwards, Esteban J. Parra

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
Topicmelanin and skin pigmentation
Canadian institutionsSickKids FoundationUniversité de MontréalMontreal Heart InstituteUniversity of Toronto
FundersAlliance de recherche numérique du Canada
KeywordsGenome-wide association studyBiologyGeneticsPolymorphism (computer science)GeneAlleleSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Abstract rs12913832, a polymorphism located in an enhancer within the HERC2 gene, which is known to regulate OCA2 transcription, is heavily relied upon as a predictor of light versus dark eyes. Individuals with the GG genotype are projected to have blue eyes, while individuals with the AA or AG genotypes are projected to have darker eye colours (primarily brown). However, eye colour is a polygenic trait, and previous studies have revealed that a significant proportion of individuals self-report an eye colour that is not concordant with their genotype at rs12913832. Herein, we address the question: What common markers are influencing eye colour in individual’s whose self-reported phenotype does not correspond to the expected phenotype based on their rs12913832 genotype? Building upon our prior investigation of iris pigmentation genetics in individuals with an expected “blue eye” background (rs12913832:GG genotype) in a sample of the Canadian Partnership for Tomorrow’s Health (CanPath) cohort, this study extends the analysis to include individuals with an expected “brown eye” background (rs12913832:AA+AG). We identified variants in SLC45A2 , TYRP1 , TYR , SLC24A4 and TSPAN10 , which may influence eye colour presentation in individuals with the rs12913832:GG genotype and variants in IRF4 , TYRP1 and OCA2 , which may influence eye colour presentation in individuals with the rs12913832:AA+AG genotype. These markers include well-known pigmentation-associated single nucleotide polymorphisms, such as rs16891982 ( SLC45A2 ), rs1126809 ( TYR ), rs12203592 ( IRF4 ), rs1800407 ( OCA2 ) and rs6420484 ( TSPAN10 ). Several of these loci were replicated using independent quantitative eye colour measures, including heterochromia and CIELAB colour dimensions. This research highlights the importance of gene-gene interactions and the polygenic nature of pigmentation traits, emphasizing modifying effects that can sometimes counteract the dominant influence of rs12913832, contributing to advancements in pigmentation genetics and forensic applications.

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)0.002
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 score0.039
Threshold uncertainty score0.077

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.010
GPT teacher head0.244
Teacher spread0.234 · 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

Citations0
Published2025
Admission routes3
Has abstractyes

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