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Record W4313528573 · doi:10.1038/s42003-022-04323-7

Rare variant analyses across multiethnic cohorts identify novel genes for refractive error

2023· article· en· W4313528573 on OpenAlexaff
Anthony M. Musolf, Annechien E. G. Haarman, Robert Luben, Jue‐Sheng Ong, Karina Patasova, Rolando Hernández Trapero, Joseph A. Marsh, Ishika Jain, Riya Jain, Paul Zhiping Wang, Deyana Lewis, Milly S. Tedja, Adriana I. Iglesias, Hengtong Li, Cameron S. Cowan, Paul N. Baird, Kathryn P. Burdon, Harry Campbell, Li Jia Chen, Ching‐Yu Cheng, Emily Y. Chew, Jamie E. Craig, Phillippa Cumberland, Margaret M. DeAngelis, Cécile Delcourt, Xiaohu Ding, David M. Evans, Qiao Fan, Maurizio Fossarello, Paul J. Foster, Puya Gharahkhani, Jeremy A. Guggenheim, Xiaobo Guo, Xikun Han, Mingguang He, Alex W. Hewitt, Quan V. Hoang, Sudha K. Iyengar, Jost B. Jonas, Mika Kähönen, Jaakko Kaprio, Barbara E.K. Klein, Jonathan H. Lass, K. Lee, Terho Lehtimäki, Qing Li, Shi‐Ming Li, Leo‐Pekka Lyytikäinen, Stuart MacGregor, David A. Mackey, Nicholas G. Martin, Akira Meguro, Candace D. Middlebrooks, Masahiro Miyake, Nobuhisa Mizuki, Stefan Nickels, Konrad Oexle, Chi Pui Pang, Andrew D. Paterson, Craig E. Pennell, Norbert Pfeiffer, Ozren Polašek, Jugnoo S. Rahi, Olli Raitakari, Igor Rudan, Srujana Sahebjada, Claire L. Simpson, E Shyong Tai, J. Willem L. Tideman, Akitaka Tsujikawa, Ningli Wang, Wen Bin Wei, Cathy Williams, Katie Williams, James F. Wilson, Robert Wojciechowski, Ya Xing Wang, Kenji Yamashiro, Jason C. Yam, Maurice Yap, Seyhan Yazar, Shea Ping Yip, Terri L. Young, Xiangtian Zhou, Ginevra Biino, Alison P. Klein, Priya Duggal, Caroline Hayward, Toomas Haller, Andres Metspalu, Juho Wedenoja, Olavi Pärssinen, Seang‐Mei Saw, Dwight Stambolian, Pirro G. Hysi, Anthony P. Khawaja, Véronique Vitart, Christopher J. Hammond, Cornelia M. van Duijn, Virginie J. M. Verhoeven, Caroline C. W. Klaver, Joan E. Bailey‐Wilson

Bibliographic record

VenueCommunications Biology · 2023
Typearticle
Languageen
FieldMedicine
TopicOphthalmology and Visual Impairment Studies
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersFP7 HealthNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesNational Human Genome Research InstituteEuropean Regional Development FundNational Institutes of HealthUniversity of California, San FranciscoOhio Lions Eye Research FoundationNational Health and Medical Research CouncilTartu ÜlikoolMedical Research CouncilGenome Institute of SingaporeWellcome TrustCancer Research UKJyväskylän YliopistoErasmus Medisch CentrumMinistero dell’Istruzione, dell’Università e della RicercaNational Eye InstituteAcademy of FinlandEesti TeadusagentuurMurdoch UniversityZonMwNational Institute of General Medical SciencesBiomedical Research CouncilRaine Medical Research FoundationCurtin University of TechnologyEuropean CommissionHorizon 2020 Framework ProgrammeHrvatska Zaklada za ZnanostNational Institute for Health and Care ResearchUniversity of CambridgeUniversity of PennsylvaniaAgency for Science, Technology and ResearchNational Medical Research CouncilKing's College LondonResearch to Prevent BlindnessUniversity of Notre DameEdith Cowan UniversityUK Research and InnovationNederlandse Organisatie voor Wetenschappelijk Onderzoek
KeywordsRefractive errorMinor allele frequencyGenome-wide association studyHeritabilityMissing heritability problem1000 Genomes ProjectGenetic associationGeneticsBiologyAlleleAllele frequencyGeneGenetic variantsSingle-nucleotide polymorphismGenotypeEye disease

Abstract

fetched live from OpenAlex

Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.

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)0.001
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 score0.184
Threshold uncertainty score0.490

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0000.001
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 head0.371
GPT teacher head0.574
Teacher spread0.202 · 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

Citations10
Published2023
Admission routes1
Has abstractyes

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