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Novel loci for ocular axial length identified through extreme-phenotype genome-wide association study in Chinese populations
  1. Xiaotong Han1,
  2. Siyu Pan2,3,
  3. Jialin Liu2,
  4. Xiaohu Ding1,
  5. Xingyan Lin1,
  6. Decai Wang1,
  7. Zhi Xie1,
  8. Changqing Zeng2,4,
  9. Fan Liu2,5,
  10. Mingguang He1,6,
  11. Xiangtian Zhou7,
  12. Tianzi Liu2,
  13. Lixia Luo1,
  14. Yizhi Liu1
  1. 1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
  2. 2 CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China
  3. 3 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
  4. 4 Institute of Biomedical Sciences, Henan Academy of Sciences, Zhengzhou, China
  5. 5 Department of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh, Saudi Arabia
  6. 6 Experimental Ophthalmology, The Hong Kong Polytechnic University, Hong Kong, China
  7. 7 Eye Hospital and School of Optometry and Ophthalmology, National Clinical Research Center for Ocular Diseases, Wenzhou Medical University, Wenzhou, China
  1. Correspondence to Dr Yizhi Liu, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China; yzliu62{at}; Professor Lixia Luo; luolixia{at}; Dr Tianzi Liu; liutz{at}; Professor Xiangtian Zhou; zhouxt2007{at}


Purpose To investigate genetic loci associated with ocular axial length (AL) in the Chinese population.

Methods A genome-wide association study meta-analysis was conducted in totalling 2644 Chinese individuals from 3 cohorts: the Guangzhou cohort (GZ, 537 high myopes and 151 hyperopes), Wenzhou cohort (334 high myopes and 6 hyperopes) and Guangzhou Twin Eye Study (1051 participants with normally distributed AL). Functional mapping was performed to annotate the significant signals, possible tissues and cell types by integrating available multiomics data. Logistic regression models using AL-associated SNPs were constructed to predict three AL status in GZ.

Results Two novel loci (1q25.2 FAM163A and 7p22.2 SDK1) showed genome-wide significant associations with AL, together explaining 29.63% of AL variance in GZ. The two lead SNPs improved the prediction accuracy for AL status, especially for hyperopes. The frequencies of AL decreasing (less myopic) alleles of the two SNPs were lowest in East Asians as compared with other populations (rs17370084: f EAS=0.03, f EUR=0.24, f AFR=0.05; rs73046501: f EAS=0.06, f EUR=0.07, f AFR=0.20), which was in line with the global distribution of myopia. The cerebral cortex and gamma-aminobutyric acidergic interneurons showed possible functional involvement in myopia development, and the galactose metabolic pathways were significantly enriched.

Conclusion Our study identified two population-specific novel loci for AL, expanding our understanding of the genetic basis of AL and providing evidence for a role of the nervous system and glucose metabolism in myopia pathogenesis.

  • Genetics
  • Epidemiology
  • Eye (Globe)

Data availability statement

Data are available upon reasonable request. The dataset of this study can be supplied on reasonable request. The data will be made available on request from the corresponding author.

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Data availability statement

Data are available upon reasonable request. The dataset of this study can be supplied on reasonable request. The data will be made available on request from the corresponding author.

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  • XH, SP and JL are joint first authors.

  • Correction notice This paper has been amended since it was first published. Two more corresponding authors have been added.

  • Contributors YL, LL, TL and XH designed the study. YL, LL, XZ and TL supervised the study and analysis. XH, XD, XL, DW and MH enrolled participants from the Guangzhou cohort, performed the animal and in vitro experiments and the genotyping and sequencing experiments. XZ enrolled participants from the Wenzhou cohort, performed genotyping and related analysis. XH, SP, JL and TL performed the data analysis. XH, SP and JL wrote the first draft. YL, LL, ZX, CZ, FL, MH and TL reviewed and revised the manuscript. LL and YL accepted full responsibility for the work, had access to all related data and made the decision to publish. All authors approved the final version of the manuscript and the decision to publish.

  • Funding This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB38010400), the National Natural Science Foundation of China (Nos 82101171 and 82070940), the Construction Project of High-Level Hospitals in Guangdong Province (No 303020102), the Science and Technology Service Network Initiative of the CAS (KFJ-STS ZDTP-079), the Henan Academy of Sciences Research Initiation Fund (232016009) and the Open Project of Key Laboratory of Genomic and Precision Medicine of the CAS. The sponsors or funding organisations had no role in the design or conduct of this research.

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  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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