Identification of novel loci influencing refractive error in East Asian populations using an extreme phenotype design |
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| Affiliation: | 1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510000, China;2. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;3. China National Center for Bioinformation, Beijing 100101, China;4. University of Chinese Academy of Sciences, Beijing 100101, China;5. School of Public Health and Preventive Medicine, Monash University, Melbourne 3800, Australia;6. Department of Surgery, Ophthalmology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria 3010, Australia;7. Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan;8. Singapore Eye Research Institute, Singapore National Eye Centre 168751, Singapore;9. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore 119077, Singapore;10. Centre for Quantitative Medicine, Duke-NUS Medical School 169857, Singapore;11. School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China;12. State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, Zhejiang 325035, China;1. Fujian Key Laboratory of Developmental and Neural Biology and Southern Center for Biomedical Research, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350117, China;2. Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA;1. State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China;2. Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, China;1. Institute of Life Sciences, College of Life and Environmental Sciences, Key Laboratory of Mammalian Organogenesis and Regeneration, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China;2. The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang 310015, China |
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| Abstract: | The global “myopia boom” has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies (GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent (SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou (631 < ?6.00D and 574 > 0.00D) and Wenzhou (593 < ?6.00D and 54 > ?1.75D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1q25.2 FAM163A, 10p11.22 NRP1/PRAD3, and 10p11.21 ANKRD30A/MTRNR2L7, together explaining 3.34% of SE variance. 10p11.21 is successfully replicated. The allele frequencies of all three loci show significant differences between major continental groups (P < 0.001). The SE reducing (more myopic) allele of rs10913877 (1q25.2 FAM163A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans (EAS = 0.60, EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities. |
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| Keywords: | Extreme phenotype Genome-wide association study Population heterogeneity Refractive error East Asian population Prediction |
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