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.
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
Br J Ophthalmol. 2024 May 21;108(6):865-872. doi: 10.1136/bjo-2023-323596.
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 and 7p22.2 ) 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: =0.03, =0.24, =0.05; rs73046501: =0.06, =0.07, =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.
在中国人中研究与眼轴长度（AL）相关的遗传基因座。
对来自 3 个队列的 2644 名中国人进行了全基因组关联研究荟萃分析：广州队列（GZ，537 名高度近视者和 151 名远视者）、温州队列（334 名高度近视者和 6 名远视者）和广州双胞胎眼研究（1051 名具有正态分布 AL 的参与者）。通过整合可用的多组学数据，进行功能映射以注释显著信号、可能的组织和细胞类型。使用与 AL 相关的 SNP 构建逻辑回归模型，以预测 GZ 中的 3 种 AL 状态。
两个新的基因座（1q25.2 和 7p22.2）与 AL 具有全基因组显著关联，共同解释了 GZ 中 29.63%的 AL 变异。两个主要 SNP 提高了对 AL 状态的预测准确性，特别是对远视者。与其他人群相比，这两个 SNP 的 AL 减少（近视程度较低）等位基因的频率在东亚人中最低（rs17370084： =0.03， =0.24， =0.05；rs73046501： =0.06， =0.07， =0.20），这与近视的全球分布一致。大脑皮层和γ-氨基丁酸能中间神经元可能参与近视的发展，并且半乳糖代谢途径显著富集。
我们的研究确定了两个与 AL 相关的新的人群特异性基因座，扩展了我们对 AL 遗传基础的理解，并为神经系统和葡萄糖代谢在近视发病机制中的作用提供了证据。
