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    Association between polygenic risk score and risk of myopia

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    Ghorbani Mojarrad_JAMA_Ophthalmology (341.0Kb)
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    Publication date
    2019-10
    Author
    Ghorbani Mojarrad, Neema
    Plotnikov, D.
    Williams, C.
    Guggenheim, J.A.
    Keyword
    Myopia
    Visual impairment
    Polygenic risk score
    Childhood myopia progression
    Rights
    This is an open access article distributed under the terms of the CC-BY License. ©2019 Ghorbani Mojarrad N et al. JAMA Ophthalmology.
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    Importance: Myopia is a leading cause of untreatable visual impairment and is increasing in prevalence worldwide. Interventions for slowing childhood myopia progression have shown success in randomized clinical trials; hence, there is a need to identify which children would benefit most from treatment intervention. Objectives: To examine whether genetic information alone can identify children at risk of myopia development and whether including a child’s genetic predisposition to educational attainment is associated with improved genetic prediction of the risk of myopia. Design, Setting, and Participants: Meta-analysis of 3 genome-wide association studies (GWAS) including a total of 711 984 individuals. These were a published GWAS for educational attainment and 2 GWAS for refractive error in the UK Biobank, which is a multisite cohort study that recruited participants between January 2006 and October 2010. A polygenic risk score was applied in a population-based validation sample examined between September 1998 and September 2000 (Avon Longitudinal Study of Parents and Children [ALSPAC] mothers). Data analysis was performed from February 2018 to May 2019. Main Outcomes and Measures: The primary outcome was the area under the receiver operating characteristic curve (AUROC) in analyses for predicting myopia, using noncycloplegic autorefraction measurements for myopia severity levels of less than or equal to −0.75 diopter (D) (any), less than or equal to -3.00 D (moderate), or less than or equal to −5.00 D (high). The predictor variable was a polygenic risk score (PRS) derived from genome-wide association study data for refractive error (n = 95 619), age of onset of spectacle wear (n = 287 448), and educational attainment (n = 328 917). Results: A total of 383 067 adults aged 40 to 69 years from the UK Biobank were included in the new GWAS analyses. The PRS was evaluated in 1516 adults aged 24 to 51 years from the ALSPAC mothers cohort. The PRS had an AUROC of 0.67 (95% CI, 0.65-0.70) for myopia, 0.75 (95% CI, 0.70-0.79) for moderate myopia, and 0.73 (95% CI, 0.66-0.80) for high myopia. Inclusion in the PRS of information associated with genetic predisposition to educational attainment marginally improved the AUROC for myopia (AUROC, 0.674 vs 0.668; P = .02), but not those for moderate and high myopia. Individuals with a PRS in the top 10% were at 6.1-fold higher risk (95% CI, 3.4–10.9) of high myopia. Conclusions and Relevance: A personalized medicine approach may be feasible for detecting very young children at risk of myopia. However, accuracy must improve further to merit uptake in clinical practice; currently, cycloplegic autorefraction remains a better indicator of myopia risk (AUROC, 0.87).
    URI
    http://hdl.handle.net/10454/17503
    Version
    Published version
    Citation
    Ghorbani Mojarrad N, Plotnikov D, Williams C et al (2019) Association between polygenic risk score and risk of myopia. JAMA Ophthalmology. 138(1): 7-13.
    Link to publisher’s version
    https://doi.org/10.1001/jamaophthalmol.2019.4421
    Type
    Article
    Collections
    Life Sciences Publications

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