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Novel loci for ocular axial length identified through extreme-phenotype genome-wide association study in Chinese populations

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机构: [1]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University [2]Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China [3]CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China [4]College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China [5]Institute of Biomedical Sciences, Henan Academy of Sciences, Zhengzhou, China [6]Department of Forensic Sciences, College of Criminal Justice, Naif Arab University for Security Sciences, Riyadh, Saudi Arabia [7]Experimental Ophthalmology, The Hong Kong Polytechnic University, Hong Kong, China [8]Eye Hospital and School of Optometry and Ophthalmology, National Clinical Research Center for Ocular Diseases, Wenzhou Medical University, Wenzhou, China
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To investigate genetic loci associated with ocular axial length (AL) in the Chinese population.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.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.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.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

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出版当年[2022]版:
大类 | 2 区 医学
小类 | 1 区 眼科学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 眼科学
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第一作者机构: [1]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University
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通讯机构: [2]Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China [*1]Beijing Institute of Genomics Chinese Academy of Sciences, Beijing, Beijing, China
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