Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration
Abstract Background Glaucoma and age-related macular degeneration (AMD) account for a substantial portion of global blindness. Both conditions are highly heritable, with recognised monogenic and polygenic inheritance patterns. Current screening guidelines lack decisive recommendations. Polygenic ris...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | BMC Ophthalmology |
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| Online Access: | https://doi.org/10.1186/s12886-023-03143-5 |
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| author | Georgina L Hollitt Ayub Qassim Daniel Thomson Joshua M Schmidt Thi Thi Nguyen John Landers Stuart MacGregor Owen M Siggs Emmanuelle Souzeau Jamie E Craig |
| author_facet | Georgina L Hollitt Ayub Qassim Daniel Thomson Joshua M Schmidt Thi Thi Nguyen John Landers Stuart MacGregor Owen M Siggs Emmanuelle Souzeau Jamie E Craig |
| author_sort | Georgina L Hollitt |
| collection | DOAJ |
| description | Abstract Background Glaucoma and age-related macular degeneration (AMD) account for a substantial portion of global blindness. Both conditions are highly heritable, with recognised monogenic and polygenic inheritance patterns. Current screening guidelines lack decisive recommendations. Polygenic risk scores (PRS) allow for cost-effective broad population risk stratification for these conditions. The predictive potential of PRS could facilitate earlier diagnosis and treatment, and prevent unnecessary vision loss. Methods The Genetic Risk Assessment of Degenerative Eye disease (GRADE) study is a prospective study designed to generate high-quality evidence about the feasibility of PRS to stratify individuals from the general population, enabling identification of those at highest risk of developing glaucoma or AMD. The targeted recruitment is 1000 individuals aged over 50 years, from which blood or saliva samples will be used for genotyping and an individual PRS for glaucoma and AMD will be derived. Individuals with PRS values in the bottom decile (n = 100), top decile (n = 100) and middle 80% (n = 100) for both glaucoma and AMD will undergo a detailed eye examination for glaucoma and/or AMD. Discussion The primary objective will be to compare the prevalence of glaucoma and AMD cases between low, intermediate, and high PRS risk groups. We expect to find a higher prevalence of both diseases in the high PRS risk group, as compared to the middle and low risk groups. This prospective study will assess the clinical validity of a PRS for glaucoma and AMD in the general Australian population. Positive findings will support the implementation of PRS into clinical practice. |
| first_indexed | 2024-03-10T22:07:56Z |
| format | Article |
| id | doaj.art-f03b3831676b4d1982b0bce8f6de8137 |
| institution | Directory Open Access Journal |
| issn | 1471-2415 |
| language | English |
| last_indexed | 2024-03-10T22:07:56Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Ophthalmology |
| spelling | doaj.art-f03b3831676b4d1982b0bce8f6de81372023-11-19T12:44:59ZengBMCBMC Ophthalmology1471-24152023-10-012311910.1186/s12886-023-03143-5Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degenerationGeorgina L Hollitt0Ayub Qassim1Daniel Thomson2Joshua M Schmidt3Thi Thi Nguyen4John Landers5Stuart MacGregor6Owen M Siggs7Emmanuelle Souzeau8Jamie E Craig9Department of Ophthalmology, Flinders UniversityDepartment of Ophthalmology, Flinders UniversityDepartment of Ophthalmology, Flinders UniversityDepartment of Ophthalmology, Flinders UniversityDepartment of Ophthalmology, Flinders UniversityDepartment of Ophthalmology, Flinders UniversityQIMR Berghofer Medical Research InstituteDepartment of Ophthalmology, Flinders UniversityDepartment of Ophthalmology, Flinders UniversityDepartment of Ophthalmology, Flinders UniversityAbstract Background Glaucoma and age-related macular degeneration (AMD) account for a substantial portion of global blindness. Both conditions are highly heritable, with recognised monogenic and polygenic inheritance patterns. Current screening guidelines lack decisive recommendations. Polygenic risk scores (PRS) allow for cost-effective broad population risk stratification for these conditions. The predictive potential of PRS could facilitate earlier diagnosis and treatment, and prevent unnecessary vision loss. Methods The Genetic Risk Assessment of Degenerative Eye disease (GRADE) study is a prospective study designed to generate high-quality evidence about the feasibility of PRS to stratify individuals from the general population, enabling identification of those at highest risk of developing glaucoma or AMD. The targeted recruitment is 1000 individuals aged over 50 years, from which blood or saliva samples will be used for genotyping and an individual PRS for glaucoma and AMD will be derived. Individuals with PRS values in the bottom decile (n = 100), top decile (n = 100) and middle 80% (n = 100) for both glaucoma and AMD will undergo a detailed eye examination for glaucoma and/or AMD. Discussion The primary objective will be to compare the prevalence of glaucoma and AMD cases between low, intermediate, and high PRS risk groups. We expect to find a higher prevalence of both diseases in the high PRS risk group, as compared to the middle and low risk groups. This prospective study will assess the clinical validity of a PRS for glaucoma and AMD in the general Australian population. Positive findings will support the implementation of PRS into clinical practice.https://doi.org/10.1186/s12886-023-03143-5GlaucomaPolygenic risk scoreGenetic testingMacular degenerationPOAGAMD |
| spellingShingle | Georgina L Hollitt Ayub Qassim Daniel Thomson Joshua M Schmidt Thi Thi Nguyen John Landers Stuart MacGregor Owen M Siggs Emmanuelle Souzeau Jamie E Craig Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration BMC Ophthalmology Glaucoma Polygenic risk score Genetic testing Macular degeneration POAG AMD |
| title | Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration |
| title_full | Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration |
| title_fullStr | Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration |
| title_full_unstemmed | Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration |
| title_short | Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration |
| title_sort | genetic risk assessment of degenerative eye disease grade study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age related macular degeneration |
| topic | Glaucoma Polygenic risk score Genetic testing Macular degeneration POAG AMD |
| url | https://doi.org/10.1186/s12886-023-03143-5 |
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