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Record W2943406899 · doi:10.1038/s42003-019-0387-5

Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development

2019· article· en· W2943406899 on OpenAlexfundno aff
Alfred Pozarickij, Cathy Williams, Pirro G. Hysi, Jeremy A. Guggenheim, Tariq Aslam, Sarah Barman, Peter Blows, Catey Bunce, Roxana O. Carare, Usha Chakravarthy, Michelle Chan, Sharon Chua, David P. Crabb, Philippa M. Cumberland, Alexander Day, Parul Desai, Bal Dhillon, Andrew D. Dick, Cathy Egan, Sarah Ennis, Paul J. Foster, Marcus Fruttiger, John Gallacher, David F. Garway‐Heath, Jane Whitney Gibson, Dan Gore, Christopher J. Hammond, Alison J. Hardcastle, Simon Harding, Ruth Hogg, Pearse A. Keane, Peng T. Khaw, Anthony P. Khawaja, Gerassimos Lascaratos, Andrew Lotery, Tom Mac Gillivray, Sarah Mackie, Keith R. Martin, Michelle McGaughey, Bernadette McGuinness, Gareth J. McKay, Martin McKibbin, Danny Mitry, Tony Moore, Zaynah Muthy, Eoin O’Sullivan, Christopher G. Owen, Praveen J. Patel, Euan Paterson, Tünde Pető, Axel Petzold, Jugnoo S. Rahi, Alicja R. Rudnikca, Jay Self, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas G. Strouthidis, Cathie Sudlow, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Véronique Vitart, S A Vernon, Ananth C. Viswanathan, Katie Williams, Jayne V. Woodside, Max Yates, Jennifer Yip, Yalin Zheng

Bibliographic record

VenueCommunications Biology · 2019
Typearticle
Languageen
FieldMedicine
TopicOphthalmology and Visual Impairment Studies
Canadian institutionsnot available
FundersMoorfields Eye Hospital NHS Foundation TrustNorthwest Regional Development AgencySight Research UKUniversity of BristolMedical Research CouncilCardiff UniversityNational Research CentreNational Institute for Health and Care ResearchMcMaster UniversityBritish Heart FoundationWellcome TrustDiabetes UK
KeywordsGenome-wide association studyBonferroni correctionGeneticsBiologyGeneGenetic associationQuantile regressionSingle-nucleotide polymorphismGenotypeStatisticsMathematics

Abstract

fetched live from OpenAlex

Abstract A genetic contribution to refractive error has been confirmed by the discovery of more than 150 associated variants in genome-wide association studies (GWAS). Environmental factors such as education and time outdoors also demonstrate strong associations. Currently however, the extent of gene-environment or gene-gene interactions in myopia is unknown. We tested the hypothesis that refractive error-associated variants exhibit effect size heterogeneity, a hallmark feature of genetic interactions. Of 146 variants tested, evidence of non-uniform, non-linear effects were observed for 66 (45%) at Bonferroni-corrected significance ( P < 1.1 × 10 −4 ) and 128 (88%) at nominal significance ( P < 0.05). LAMA2 variant rs12193446, for example, had an effect size varying from −0.20 diopters (95% CI −0.18 to −0.23) to −0.89 diopters (95% CI −0.71 to −1.07) in different individuals. SNP effects were strongest at the phenotype extremes and weaker in emmetropes. A parsimonious explanation for these findings is that gene-environment or gene-gene interactions in myopia are pervasive.

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)0.000
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 score0.043
Threshold uncertainty score0.477

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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 head0.246
GPT teacher head0.484
Teacher spread0.238 · 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

Citations49
Published2019
Admission routes1
Has abstractyes

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