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Volume 49 Issue 1
Jan.  2022
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Article Contents

Identification of novel loci influencing refractive error in East Asian populations using an extreme phenotype design

doi: 10.1016/j.jgg.2021.08.011
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We thank the many thousands of people participating in this study and also thank Mr. Xingjian Gao from Beijing Institute of Genomics, Chinese Academy of Sciences for help with the statistical analysis. This work was supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDB38010400), National Key R&D Program of China (2018YFC0116500), Science and Technology Service Network Initiative of Chinese Academy of Sciences (KFJ-STS-ZDTP-079), Science and Technology Planning Project of Guangdong Province (2013B20400003), the Fundamental Research Funds of the State Key Laboratory of Ophthalmology, and the Open Project of Key Laboratory of Genomic and Precision Medicine of the CAS. X.H. was supported by the China Scholarship Council (CSC) and China Postdoctoral Science Foundation (2019TQ0365). The sponsors or funding organizations had no role in the design or conduct of this research.

  • Received Date: 2021-04-27
  • Accepted Date: 2021-08-12
  • Rev Recd Date: 2021-08-09
  • Publish Date: 2021-09-11
  • 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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