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

Study Protocol

Ayub Qassim¹  John Landers¹  Daniel Thomson¹  Joshua M Schmidt¹  Jamie E Craig¹  Thi Thi Nguyen¹  Emmanuelle Souzeau¹  Georgina L Hollitt¹  Owen M Siggs²  Stuart MacGregor³ 

[1] Department of Ophthalmology, Flinders University, 1 Flinders Drive, 5042, Bedford Park, SA, Australia;Department of Ophthalmology, Flinders University, 1 Flinders Drive, 5042, Bedford Park, SA, Australia;Garvan Institute of Medical Research, 2010, Darlinghurst, NSW, Australia;QIMR Berghofer Medical Research Institute, 4006, Herston, QLD, Australia;

关键词: Glaucoma;    Polygenic risk score;    Genetic testing;    Macular degeneration;    POAG;    AMD;   

DOI  :  10.1186/s12886-023-03143-5

 received in 2023-04-19, accepted in 2023-09-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGlaucoma 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.MethodsThe 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.DiscussionThe 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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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