Genetic Variants on Chromosome 1q41 Influence Ocular Axial Length and High Myopia

被引：85

作者：

Fan, Qiao ^{[1
]}

Barathi, Veluchamy A. ^{[2
,3
]}

Cheng, Ching-Yu ^{[1
,2
,3
]}

Zhou, Xin ^{[1
]}

Meguro, Akira ^{[4
]}

Nakata, Isao ^{[5
,6
,7
]}

Khor, Chiea-Chuen ^{[2
,8
,9
,10
]}

Goh, Liang-Kee ^{[1
,11
,12
]}

Li, Yi-Ju ^{[13
,14
]}

Lim, Wan'e ^{[2
]}

Ho, Candice E. H. ^{[2
]}

Hawthorne, Felicia ^{[14
]}

Zheng, Yingfeng ^{[2
]}

Chua, Daniel ^{[2
]}

Inoko, Hidetoshi ^{[15
]}

Yamashiro, Kenji ^{[5
]}

Ohno-Matsui, Kyoko ^{[16
]}

Matsuo, Keitaro ^{[17
]}

Matsuda, Fumihiko ^{[6
,7
]}

Vithana, Eranga ^{[2
,3
]}

Seielstad, Mark ^{[18
,19
]}

Mizuki, Nobuhisa ^{[4
]}

Beuerman, Roger W. ^{[2
,3
,11
]}

Tai, E. -Shyong ^{[1
,20
]}

Yoshimura, Nagahisa ^{[5
]}

Aung, Tin ^{[2
,3
]}

Young, Terri L. ^{[11
,14
]}

Wong, Tien-Yin ^{[1
,2
,3
,21
]}

Teo, Yik-Ying ^{[1
,8
,22
,23
]}

Saw, Seang-Mei ^{[1
,2
,3
,11
,22
]}

机构：

[1] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore

[2] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore

[3] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore

[4] Yokohama City Univ, Sch Med, Dept Ophthalmol, Yokohama, Kanagawa 232, Japan

[5] Kyoto Univ, Dept Ophthalmol, Grad Sch Med, Kyoto 606, Japan

[6] Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto, Japan

[7] Kyoto Univ, INSERM, U852, Grad Sch Med, Kyoto, Japan

[8] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore

[9] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore

[10] Natl Univ Singapore, Dept Pediat, Singapore 117548, Singapore

[11] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore

[12] Natl Canc Ctr Singapore, Dept Med Oncol, Singapore, Singapore

[13] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA

[14] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA

[15] Tokai Univ, Sch Med, Dept Mol Life Sci, Div Mol Med Sci & Mol Med, Isehara, Kanagawa 25911, Japan

[16] Tokyo Med & Dent Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Tokyo, Japan

[17] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan

[18] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[19] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA

[20] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore

[21] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia

[22] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore

[23] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore

来源：

PLOS GENETICS | 2012年 / 8卷 / 06期

基金：

新加坡国家研究基金会; 英国医学研究理事会; 美国国家卫生研究院; 日本学术振兴会;

关键词：

GENOME-WIDE ASSOCIATION; SINGAPORE MALAY EYE; BEAVER DAM EYE; REFRACTIVE ERRORS; RISK-FACTORS; PATHOLOGICAL COMPLICATIONS; SUSCEPTIBILITY LOCUS; ZINC TRANSPORTERS; MESSENGER-RNA; ONSET MYOPIA;

D O I：

10.1371/journal.pgen.1002753

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, beta = -0.16 mm per minor allele, P-meta = 2.69x10(-10)). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) = 0.75, 95% CI: 0.68-0.84, P-meta = 4.38x10(-7)) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.

引用

页数：14

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