Li, Sze Wai Rosa, He, Xi, Terry, Louise, Verhoeven, Virginie J. M., Lee, Samantha Sze-Yee, Lingham, Gareth, Guggenheim, Jeremy A.  ORCID: https://orcid.org/0000-0001-5164-340X, Mackey, David A., Saw, Seang-Mei, Klaver, Caroline C. W. and Pang, Chi Pui
2025.
Advances in the genetics of refractive errors: Contributions from the CREAM consortium.
Acta Ophthalmologica
10.1111/aos.70025
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Abstract
The Consortium for Refractive Error and Myopia (CREAM) was established in 2011, bringing together an international team of researchers studying more than 30 cohorts. Since its establishment, CREAM has played a pivotal role in research investigating the genetics of myopia and other refractive errors, serving as a key driver of progress in the field. The aim of this review is to highlight the latest advances and insights from CREAM, with a focus on research carried out in the past 5 years. We performed a literature review of journal articles authored by the CREAM consortium since the year 2020, when the last review of CREAM consortium findings was published. Key discoveries from recent CREAM studies were the identification of SIX6, CRX, PER3, PDCD6IP, MAPT, CHST6, GRHL2, USH2A, P4HTM, COL4A4 and ATM as high-confidence candidate genes associated with myopia development. Variants in enhancers and lncRNA regions were shown to have potential regulatory effects on refractive error; the DDIT4 gene was highlighted as a potential hotspot for future analyses. A polygenic risk score for predicting high myopia with an area under the curve (AUC) accuracy of 0.78 was made openly available; prediction accuracy was close to that required for clinical use. A shared genetic architecture for refractive error and axial length was confirmed. Novel findings were the identification of rare, large-effect gene variants through targeted and whole exome sequencing and the development of a polygenic risk score for predicting children at risk of developing high myopia. Large-scale multi-ancestry genome-wide association studies of the myopia endophenotypes axial length and corneal curvature doubled the number of common genetic variants known to be associated with these traits. Nevertheless, much remains to be done to fulfil the promise of myopia genetics research for improving the detection of children at above-average risk of high myopia, and the prevention and treatment of myopia.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | In Press |
| Schools: | Schools > Optometry and Vision Sciences |
| Publisher: | Wiley |
| ISSN: | 1755-375X |
| Funders: | UKRI EP/Y032292/1 |
| Date of First Compliant Deposit: | 13 November 2025 |
| Date of Acceptance: | 28 October 2025 |
| Last Modified: | 14 Nov 2025 11:00 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/182394 |
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