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: fEAS=0.03, fEUR=0.24, fAFR=0.05; rs73046501: fEAS=0.06, fEUR=0.07, fAFR=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.
- 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.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
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.
Map disclaimer The inclusion of any map (including the depiction of any boundaries therein), or of any geographic or locational reference, does not imply the expression of any opinion whatsoever on the part of BMJ concerning the legal status of any country, territory, jurisdiction or area or of its authorities. Any such expression remains solely that of the relevant source and is not endorsed by BMJ. Maps are provided without any warranty of any kind, either express or implied.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.