Abstract
PurposeTo investigate genetic loci associated with ocular axial length (AL) in the Chinese population.MethodsA 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.ResultsTwo novel loci (1q25.2FAM163Aand 7p22.2SDK1) 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.ConclusionOur 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.
Funder
Bureau of Frontier Sciences and Education, Chinese Academy of Sciences
Construction Project of High-Level Hospitals in Guangdong Province
National Natural Science Foundation of China
Open Project of Key Laboratory of Genomic and Precision Medicine of Chinese Academy of Sciences
Science and Technology Service Network Plan
Henan Academy of Sciences Research Initiation Fund
Subject
Cellular and Molecular Neuroscience,Sensory Systems,Ophthalmology
Cited by
1 articles.
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