A genome-wide meta-analysis identifies two novel loci associated with high myopia in the Han Chinese population
A genome-wide meta-analysis identifies two novel loci associated with high myopia in the Han Chinese population
复制标题
全基因组荟萃分析确定了与中国汉族人群高度近视相关的两个新位点
DOI：
10.1093/hmg/ddt066
复制
发表时间：
2013-06-01
影响因子：
3.5
通讯作者：
Yang, Zhenglin
中科院分区：
文献类型：
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作者：
Shi, Yi;Gong, Bo;Yang, Zhenglin
高度近视在中国人群中非常普遍，是全球视力损害的主要原因。遗传因素在这种视觉障碍的发展中起着关键作用。近年来的全基因组关联研究揭示了几个有助于其进展的染色体区域。为了确定高度近视易感性的其他遗传变异，我们使用全基因组荟萃分析来检查665例病例和960例对照的联合队列中的疾病与286 031个单核苷酸多态性（SNP）之间的关联。在一个重复队列（850例病例和1197例对照）中对最显著的SNP（n 61）进行基因分型，并在另外两个验证队列（1278例病例和2486例对照）中通过基因分型对14个SNP进行进一步检测。作为该分析的结果，4个SNP达到全基因组显著性（P 2.0 10（7））。最显著相关的SNP rs 2730260 [总体P 8.95 10（14）;比值比（95 CI）1.33（1.231.44）]位于MYP 4基因座的VIPR 2基因中。位于同一连锁不平衡区的其他3个SNPs（rs7839488、rs 4395927和rs 4455882）均位于SNTB 1基因，P值在1.13 × 10（8）~ 2.13 × 10（11）之间。VIPR 2和SNTB 1基因在视网膜和视网膜色素上皮中表达，并且先前已报道其在近视的发病机制中具有潜在功能。我们的研究结果表明，VIPR 2和SNTB 1基因的变异增加了中国汉族人高度近视的易感性。
High myopia, highly prevalent in the Chinese population, is a leading cause of visual impairment worldwide. Genetic factors play a critical role in the development of this visual disorder. Genome-wide association studies in recent years have revealed several chromosomal regions that contribute to its progression. To identify additional genetic variants for high myopia susceptibility, we used a genome-wide meta-analysis to examine the associations between the disease and 286 031 single-nucleotide polymorphisms (SNPs) in a combined cohort of 665 cases and 960 controls. The most significant SNPs (n 61) were genotyped in a replication cohort (850 cases and 1197 controls), and 14 SNPs were further tested through genotyping in two additional validation cohorts (combined 1278 cases and 2486 controls). As a result of this analysis, four SNPs reached genome-wide significance (P 2.0 10(7)). The most significantly associated SNP, rs2730260 [overall P 8.95 10(14); odds ratio (95 CI) 1.33 (1.231.44)], is located in the VIPR2 gene, which is located in the MYP4 locus. The other three SNPs (rs7839488, rs4395927 and rs4455882) in the same linkage disequilibrium block are located in the SNTB1 gene, with P values ranging from 1.13 10(8) to 2.13 10(11). The VIPR2 and SNTB1 genes are expressed in the retina and the retinal pigment epithelium and have been previously reported to have potential functions for the pathogenesis of myopia. Our results suggest that variants of the VIPR2 and SNTB1 genes increase susceptibility to high myopia in Han Chinese.