title: A genome-wide association study reveals association between common variants in an intergenic region of 4q25 and high-grade myopia in the Chinese Han population.
abstract: High-grade myopia (HM) is highly heritable, and has a high prevalence in the Han Chinese population. We carried out a genome-wide association study involving 102 HM cases suffering from retinal degeneration, and 335 controls who were free from HM and fundus diseases. Significant single-nucleotide polymorphisms were replicated in two follow-up studies: stage I involved 2628 independent cases and 9485 controls, and stage II involved a further 263 cases and 586 HM-free controls. The results were combined in a meta-analysis. Cases and controls were drawn from the Chinese Han population. A locus in an intergenic region at 4q25, within MYP11 (4q22-q27, OMIM: 609994), was found to be associated with HM (rs10034228, P(meta) = 7.70 × 10(-13), allelic odds ratio = 0.81, 95% confidence interval 0.76-0.86). There are no known genes in the region but a number of expressed sequence tags (ESTs) have been located there, one of which (BI480957) has been reported to express in the native human retinal pigment epithelium. In addition, a predicted gene was identified in this region. The gene's predicted protein sequence is highly similar to tubulin, beta 8 and beta-tubulin 4Q. Several previous studies have shown that tubulin plays an important role in eye development. Our result is compatible with a previous linkage study in the Han Chinese population (mapping in MYP11, 4q22-q27), and provides a more accurate locus for HM. Although there is insufficient evidence to indicate that expressed EST and the predicted gene play an important role in developing HM, this region merits further study as a candidate for the disease.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.forename: Xiangtian
authors.initials: X
authors.lastname: Zhou
authors.forename: Haidong
authors.initials: H
authors.lastname: Zou
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Hu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Wenjin
authors.initials: W
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Zangdong
authors.initials: Z
authors.lastname: He
authors.forename: Jue
authors.initials: J
authors.lastname: Ji
authors.forename: Ti
authors.initials: T
authors.lastname: Wang
authors.forename: Junyan
authors.initials: J
authors.lastname: Li
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Guoyin
authors.initials: G
authors.lastname: Feng
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000483:Alleles; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D002681:China / Q000208:ethnology; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics* / Q000378:metabolism; D020224:Expressed Sequence Tags / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D030342:Genetic Diseases, Inborn / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008040:Genetic Linkage; D056426:Genetic Loci / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D047728:Myopia, Degenerative / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D055213:Retinal Pigment Epithelium / Q000378:metabolism
chemical_list: D021901:DNA, Intergenic