Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images
| Autor: | Alice Pébay, Jue-Sheng Ong, Alberta A H J Thiadens, UK Biobank Eye, Jamie E. Craig, Denize Atan, Anne Senabouth, Michiaki Kubo, Caroline C W Klaver, Hélène Choquet, Puya Gharahkhani, Hannah Currant, Mark James Simcoe, Janey L Wiggs, Paul J. Foster, Charles A Reisman, David A. Mackey, Stuart MacGregor, Cornelia M. van Duijn, Maciej S. Daniszewski, Pirro G. Hysi, Anthony P Khawaja, Alex W. Hewitt, Louis R. Pasquale, Seyhan Yazar, Pieter W.M. Bonnemaijer, Peng T. Khaw, Jason Charng, Tin Aung, Joseph E. Powell, Tomas W Fitzgerald, Ewan Birney, Christopher J Hammond, Eric Jorgenson, Praveen J. Patel |
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| Přispěvatelé: | Consortium, UK Biobank Eye and Vision, Consortium, International Glaucoma Genetics, Epidemiology, Ophthalmology |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Visual acuity Eye Diseases genetic structures Vision Single Nucleotide Polymorphisms Nerve fiber layer Visual Acuity Social Sciences Glaucoma QH426-470 Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] chemistry.chemical_compound Medical Conditions Mathematical and Statistical Techniques 0302 clinical medicine Foveal Medicine and Health Sciences Psychology Genetics (clinical) Biological Specimen Banks 0303 health sciences Statistics Genomics Metaanalysis Middle Aged Hypoplasia medicine.anatomical_structure Phenotype Physical Sciences Sensory Perception Female Anatomy medicine.symptom Tomography Optical Coherence Research Article Quality Control medicine.medical_specialty Genotype Ocular Anatomy Vision Disorders Biology Research and Analysis Methods Polymorphism Single Nucleotide Retina 03 medical and health sciences SDG 3 - Good Health and Well-being Ocular System Ophthalmology Genome-Wide Association Studies medicine Genetics Humans Statistical Methods Hair Color Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Cognitive Psychology Biology and Life Sciences Computational Biology Correction Genetic Variation Human Genetics Retinal Genome Analysis medicine.disease Inner plexiform layer United Kingdom eye diseases chemistry Genetic Loci 030221 ophthalmology & optometry Eyes Cognitive Science Perception sense organs Head Mathematics Neuroscience |
| Zdroj: | PLoS Genetics, Vol 17, Iss 10 (2021) PLoS Genetics Plos Genetics, 17 Plos Genetics, 17, 5 PLoS Genetics, Vol 17, Iss 5, p e1009497 (2021) PLoS Genetics, Vol 17, Iss 10, p e1009858 (2021) PLoS Genetics, 17(5):e1009497. Public Library of Science 2021, ' Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images ', PLoS Genetics, vol. 17, no. 5, e1009497, pp. e1009497 . https://doi.org/10.1371/journal.pgen.1009497 |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function. Author summary The thickness of the inner retinal layers is one of the biomarkers for glaucoma, the leading cause of irreversible blindness globally. Here we utilised the large-scale of the UK Biobank and the images of the retina it contains to look for genetic variants that effect the thickness of the inner retina. We find many variants associated with this variable, but surprisingly only one that also affects glaucoma. Further analysis shows that glaucoma and genetically determined inner retinal thickness are not on the same genetic pathway and it is rather the change of thickness over time that is indicative of the disease. This is important as it invites the potential for the discovered variants to be used as a representation of baseline thickness in the clinic in the future. We also show that foveal hypoplasia, the lack of the normal valley-like shape of the central retina, is present at a population level in a mild form and is affected by three variants that also affect visual acuity. This is an interesting discovery as foveal hypoplasia was previously thought of as an outcome of rare Mendelian disease. |
| Databáze: | OpenAIRE |
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