ArticleInvestigative ophthalmology & visual science2015
Accurate Imputation-Based Screening of Gln368Ter Myocilin Variant in Primary Open-Angle Glaucoma.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.Nature communications · 2021Pooled it
- Progress in Translating Glaucoma Genetics Into the Clinic: A Review.Clinical & experimental ophthalmology · 2025Review
- Matrix Mechanotransduction via Yes-Associated Protein in Human Lamina Cribrosa Cells in Glaucoma.Investigative ophthalmology & visual science · 2022Article
- Characteristics of p.Gln368Ter Myocilin Variant and Influence of Polygenic Risk on Glaucoma Penetrance in the UK Biobank.Ophthalmology · 2021Article
- Myocilin-associated Glaucoma: A Historical Perspective and Recent Research Progress.Molecular vision · 2021Review
- Myocilin Mutations in Patients With Normal-Tension Glaucoma.JAMA ophthalmology · 2019Article
- Myocilin Gene Gln368Ter Variant Penetrance and Association With Glaucoma in Population-Based and Registry-Based Studies.JAMA ophthalmology · 2019Article
- Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study.Nature communications · 2018Article
- Major review: Molecular genetics of primary open-angle glaucoma.Experimental eye research · 2017Review
- Differential response and withdrawal profile of glucocorticoid-treated human trabecular meshwork cells.Experimental eye research · 2017Article
- Ethical Considerations for the Return of Incidental Findings in Ophthalmic Genomic Research.Translational vision science & technology · 2016Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
purposeMyocilin (MYOC) is a well-established primary open-angle glaucoma (POAG) risk gene, with rare variants known to have high penetrance. The most common clinically relevant risk variant, Gln368Ter, has an allele frequency of 0.1% to 0.3% in populations of European ancestry. Detection of rare MYOC variants has traditionally been conducted using Sanger sequencing. Here we report the use of genotyping arrays and imputation to assess whether rare variants including Gln368Ter can be reliably detected.
methodsA total of 1155 cases with advanced POAG and 1992 unscreened controls genotyped on common variant arrays participated in this study. Accuracy of imputation of Gln368Ter variants was compared with direct sequencing. A genome-wide association study was performed using additive model adjusted for sex and the first six principal components.
resultsWe found that although the arrays we used were designed to tag common variants, we could reliably impute the Gln368Ter variant (rs74315329). When tested in 1155 POAG cases and 1992 controls, rs74315329 was strongly associated with risk (odds ratio = 15.53, P = 1.07 × 10-9). All POAG samples underwent full sequencing of the MYOC gene, and we found a sensitivity of 100%, specificity of 99.91%, positive predictive value of 95.65%, and negative predictive value of 100% between imputation and sequencing. Gln368Ter was also accurately imputed in a further set of 1801 individuals without POAG. Among the total set of 3793 (1992 + 1801) individuals without POAG, six were predicted (probability > 95%) to carry the risk variant.
conclusionsWe demonstrate that some clinically important rare variants can be reliably detected using arrays and imputation. These results have important implications for the detection of clinically relevant incidental findings in ongoing and future studies using arrays.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.