Genetic Variants at 13q12.12 Are Associated with High Myopia in the Han Chinese Population
Genetic Variants at 13q12.12 Are Associated with High Myopia in the Han Chinese Population
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13q12.12 基因变异与中国汉族人群高度近视相关
DOI：
10.1016/j.ajhg.2011.04.022
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发表时间：
2011-06-10
影响因子：
9.8
通讯作者：
Yang, Zhenglin
中科院分区：
文献类型：
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作者：
Shi, Yi;Qu, Jia;Yang, Zhenglin
高度近视在中国人中非常普遍，是世界上导致失明的主要原因之一。遗传因素在该病的发展中起着关键作用。为了确定与高度近视相关的遗传变异，我们对来自中国汉族队列的1088名个体(419例和669名对照)的493,947个SNP进行了全基因组关联研究，并在三个独立的队列(合并，2803例和5642名对照)中跟踪了与P<；1.0 x 10(-4)相关的信号。我们发现高度近视与13q12.12上的一个变异显著相关(rs9318086，合并p=1.91 x 10(-16)，杂合优势比=1.32，纯合子优势比=1.64)。此外，在与rs9318086相同的连锁不平衡(LD)区块中，另外5个SNP(rs9510902、rs3794338、rs1886970、rs7325450和rs7331047)也被证明与中国汉族人群的高度近视显著相关，p值在5.46×10(-11)到6.16×10(-16)之间。该相关基因包含三个基因：MIPEP、C1QTNF9B-AS1和C1QTNF9B。MIPEP和C1QTNF9B在视网膜和视网膜色素上皮(RPE)中表达，并比C1QTNF9B-AS1更有可能与高度近视相关，因为有证据表明视网膜信号控制眼睛的生长。我们的结果表明13q12.12的变异与高度近视有关。
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 x 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 x 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 x 10(-11) to 6.16 x 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.