{"doi":"10.1016/j.ebiom.2023.104551","title":"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","abstract":"BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).","journal":"EBioMedicine","year":2023,"id":324611,"datarank":0.748849626709143,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"self_citation_contribution":0.5289540786924243,"citation_network_contribution":0.21989554801671876,"self_endowment_contribution":0.5289540786924243,"citer_contribution":0.21989554801671876,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":17,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1041300,"name":"Samantha Sze‐Yee Lee","orcid":"0000-0001-6635-1098","position":1,"is_corresponding":false},{"id":1041301,"name":"Ran Du","orcid":"0000-0002-8916-775X","position":2,"is_corresponding":false},{"id":1041302,"name":"Yining Wang","orcid":"0000-0001-6441-2002","position":3,"is_corresponding":false},{"id":1041303,"name":"Sander C. 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