A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration.


Clark, Rosie, Lee, Samantha Sze-Yee, Du, Ran, Wang, Yining, Kneepkens, Sander CM, Charng, Jason ORCID: 0000-0002-5778-6310, Huang, Yu, Hunter, Michael L ORCID: 0000-0001-6704-4815, Jiang, Chen, Tideman, J Willem L et al (show 9 more authors) (2023) A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration. EBioMedicine, 91. 104551-.

[img] PDF
A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of t.pdf - Open Access published version
Download (2MB) | Preview

Abstract

<h4>Background</h4>High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER.<h4>Methods</h4>The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression.<h4>Findings</h4>In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24).<h4>Interpretation</h4>Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for.<h4>Funding</h4>Supported by the Welsh Government and Fight for Sight (24WG201).

Item Type: Article
Uncontrolled Keywords: CREAM Consortium, UK Biobank Eye and Vision Consortium, Humans, Myopia, Macular Degeneration, Adult, Child, Genome-Wide Association Study, Ethnicity, Asian People, African People, South Asian People, European People, East Asian People
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 23 Jun 2023 09:46
Last Modified: 23 Jun 2023 09:46
DOI: 10.1016/j.ebiom.2023.104551
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3171230
Dimensions
Altmetric
CORE (COnnecting REpositories)