title: A genome-wide meta-analysis identifies two novel loci associated with high myopia in the Han Chinese population.
abstract: 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 (1.23-1.44)], 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.
authors: The Sichuan Provincial Key Laboratory for Human Disease Gene Study, The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610072, China.
authors: Yi
authors: Y
authors: Shi
authors: Bo
authors: B
authors: Gong
authors: Lijia
authors: L
authors: Chen
authors: Xianbo
authors: X
authors: Zuo
authors: Xiaoqi
authors: X
authors: Liu
authors: Pancy O S
authors: PO
authors: Tam
authors: Xiangtian
authors: X
authors: Zhou
authors: Peiquan
authors: P
authors: Zhao
authors: Fang
authors: F
authors: Lu
authors: Jia
authors: J
authors: Qu
authors: Liangdan
authors: L
authors: Sun
authors: Fuxin
authors: F
authors: Zhao
authors: Haoyu
authors: H
authors: Chen
authors: Yiping
authors: Y
authors: Zhang
authors: Dingding
authors: D
authors: Zhang
authors: Ying
authors: Y
authors: Lin
authors: He
authors: H
authors: Lin
authors: Shi
authors: S
authors: Ma
authors: Jing
authors: J
authors: Cheng
authors: Jiyun
authors: J
authors: Yang
authors: Lulin
authors: L
authors: Huang
authors: Mingzhi
authors: M
authors: Zhang
authors: Xuejun
authors: X
authors: Zhang
authors: Chi Pui
authors: CP
authors: Pang
authors: Zhenglin
authors: Z
authors: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002681:China; D049029:Dystrophin-Associated Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics; D055815:Young Adult
chemical_list: D049029:Dystrophin-Associated Proteins; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; C091824:syntrophin