The Sichuan Provincial Key Laboratory for Human Disease Gene Study and The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
Am J Hum Genet. 2011 Jun 10;88(6):805-813. doi: 10.1016/j.ajhg.2011.04.022. Epub 2011 Jun 6.
High myopia, which is extremely prevalent in the Chinese population, is one of the leading causes of blindness in the world. Genetic factors play a critical role in the development of the condition. To identify the genetic variants associated with high myopia in the Han Chinese, we conducted a genome-wide association study (GWAS) of 493,947 SNPs in 1088 individuals (419 cases and 669 controls) from a Han Chinese cohort and followed up on signals that were associated with p < 1.0 × 10(-4) in three independent cohorts (combined, 2803 cases and 5642 controls). We identified a significant association between high myopia and a variant at 13q12.12 (rs9318086, combined p = 1.91 × 10(-16), heterozygous odds ratio = 1.32, and homozygous odds ratio = 1.64). Furthermore, five additional SNPs (rs9510902, rs3794338, rs1886970, rs7325450, and rs7331047) in the same linkage disequilibrium (LD) block with rs9318086 also proved to be significantly associated with high myopia in the Han Chinese population; p values ranged from 5.46 × 10(-11) to 6.16 × 10(-16). This associated locus contains three genes-MIPEP, C1QTNF9B-AS1, and C1QTNF9B. MIPEP and C1QTNF9B were found to be expressed in the retina and retinal pigment epithelium (RPE) and are more likely than C1QTNF9B-AS1 to be associated with high myopia given the evidence of retinal signaling that controls eye growth. Our results suggest that the variants at 13q12.12 are associated with high myopia.
高度近视在中国人群中极为普遍，是全球致盲的主要原因之一。遗传因素在该疾病的发展中起着关键作用。为了确定与汉族人群高度近视相关的遗传变异，我们对一个汉族人群的 1088 名个体（419 例病例和 669 例对照）进行了全基因组关联研究（GWAS），共检测了 493947 个 SNP，并对在三个独立队列中与 p < 1.0 × 10(-4)相关的信号进行了随访（合并，2803 例病例和 5642 例对照）。我们发现高度近视与 13q12.12 上的一个变异存在显著关联（rs9318086，合并 p = 1.91 × 10(-16)，杂合优势比 = 1.32，纯合优势比 = 1.64）。此外，在与 rs9318086 处于相同连锁不平衡（LD）块的 5 个额外 SNP（rs9510902、rs3794338、rs1886970、rs7325450 和 rs7331047）也被证明与汉族人群的高度近视显著相关；p 值范围从 5.46 × 10(-11)到 6.16 × 10(-16)。该关联位点包含三个基因-MIPEP、C1QTNF9B-AS1 和 C1QTNF9B。MIPEP 和 C1QTNF9B 在视网膜和视网膜色素上皮（RPE）中表达，鉴于控制眼球生长的视网膜信号证据，它们比 C1QTNF9B-AS1 更有可能与高度近视相关。我们的研究结果表明，13q12.12 上的变异与高度近视相关。
