Multi-ancestry genome-wide association analyses of refractive error augment genetic discovery and polygenic prediction

Refractive errors (REs) affect over half of the global population, with consequences ranging from blurred vision to blindness. Here we conducted ancestry-stratified and cross-ancestry meta-analyses of genome-wide association studies for RE in people of European (n = 1,495,159), East Asian (n = 121,172) and African (n = 144,737) ancestries. The cross-ancestry meta-analysis identified 932 RE-associated variants, including 241 previously unknown associations, four East Asian-specific associations and one African-specific association. Statistical fine-mapping pinpointed 16 high-confidence putative causal variants, and gene prioritization analyses highlighted 23 genes involved in eye development. We constructed an enhanced polygenic predictor incorporating functional annotations that explained 21.4% of RE variation, effectively stratified the onset, progression and severity of myopia, and achieved an area under the receiver operating characteristic curve of 0.806 for predicting high myopia. Our multi-ancestry genome-wide association study expands substantially the catalog of genetic variants for RE and demonstrates the potential clinical utility of polygenic prediction in identifying high-risk people across diverse populations.

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Journal
Nature Genetics
Published
2026-04-20
DOI
https://doi.org/10.1038/s41588-026-02576-0
Primary Topic
Ophthalmology and Visual Impairment Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Multi-ancestry genome-wide association analyses of refractive error augment genetic discovery and polygenic prediction

Yuki Ishikawa, Chikashi C. Terao, Ethan M. Jewett, R. Ryanne Wu et al.
Nature Genetics
Ophthalmology and Visual Impairment Studies
article

Multi-ancestry genome-wide association analyses of refractive error augment genetic discovery and polygenic prediction

Yuki Ishikawa, Chikashi C. Terao, Ethan M. Jewett, R. Ryanne Wu, Anjali J. Shastri, G. David Poznik, Mari Nelis, Emily Rios, Julia Sidorenko, Gang Chen, Bertram L. Koelsch, Jian Zeng, Anna Guan, Lili Milani, Ruth I. Tennen, Jingran Wen, Steven J. Micheletti, Nobuhisa Mizuki, Adam Auton, Alisa P. Lehman, William A. Freyman, Aditya Ambati, Chris German, Teng Li, Keiko Hikino, Alan Kwong, Fei-Fei Cheng, Ruilei Ma, Reedik Mägi, Éadaoin Harney, Catherine H. Weldon, Peter Wilton, James R. Ashenhurst, Andres Metspalu, Qiaojuan Jane Su, Senwei Tang, Hélène Choquet, Emily DelloRusso, Wanwan Xu, Masaki Takeuchi, Lizhong Wang, K. Bond, Matthew H. McIntyre, Rebecca M. K. Berns, Stella Aslibekyan, Matthew J. Kmiecik, Robert K. Bell, Kahsaia de Brito, Sayantan Das, David A. Hinds, Shubham Saini, Keng-Han Lin, Joyce Y. Tung, Vinh Tran, Kun Zhou, Ruoyan Chen, Stacey B. Detweiler, Georgi Hudjashov, Tõnu Esko, Xiaoxi Liu, Zi-Bing Jin, Noura S. Abul-Husn, Chen Jiang, Tania Islam, Yazhou Guo, Akira Meguro, Barry Hicks, Hao Mi, Likun Wang
article en

Abstract

Refractive errors (REs) affect over half of the global population, with consequences ranging from blurred vision to blindness. Here we conducted ancestry-stratified and cross-ancestry meta-analyses of genome-wide association studies for RE in people of European (n = 1,495,159), East Asian (n = 121,172) and African (n = 144,737) ancestries. The cross-ancestry meta-analysis identified 932 RE-associated variants, including 241 previously unknown associations, four East Asian-specific associations and one African-specific association. Statistical fine-mapping pinpointed 16 high-confidence putative causal variants, and gene prioritization analyses highlighted 23 genes involved in eye development. We constructed an enhanced polygenic predictor incorporating functional annotations that explained 21.4% of RE variation, effectively stratified the onset, progression and severity of myopia, and achieved an area under the receiver operating characteristic curve of 0.806 for predicting high myopia. Our multi-ancestry genome-wide association study expands substantially the catalog of genetic variants for RE and demonstrates the potential clinical utility of polygenic prediction in identifying high-risk people across diverse populations.

Nature Genetics
Beijing Tongren Hospital (CN), Kaiser Permanente (US), Central South University (CN), University of Shizuoka (JP), Chulalongkorn University (TH), The University of Queensland (AU), Capital Medical University (CN), Peking University (CN), QIMR Berghofer Medical Research Institute (AU), Westlake University (CN), Dongfang Electric Corporation (China) (CN), Shenzhen Weiguang Biological Products (China) (CN), Palo Alto Institute (US), Shizuoka General Hospital (JP), RIKEN Center for Integrative Medical Sciences (JP), Kai Biotech (South Korea) (KR), University of Tartu (EE), Yokohama City University (JP)
Westlake University, Medical Research Council, National Health and Medical Research Council
Openalex Percentile: Top 17%
Ophthalmology and Visual Impairment Studies
DOIOpen Access PDFOpenAlex
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