Genetic Variants at 13q12.12 Are Associated with High Myopia in the Han Chinese Population

被引：93

作者：

Shi, Yi ^{[1
,2
]}

Qu, Jia ^{[3
]}

Zhang, Dingding ^{[1
,2
]}

Zhao, Peiquan ^{[4
]}

Zhang, Qingjiong ^{[5
]}

Tam, Pancy Oi Sin ^{[6
]}

Sun, Liangdan ^{[7
]}

Zuo, Xianbo ^{[7
]}

Zhou, Xiangtian ^{[3
]}

Xiao, Xueshan ^{[5
]}

Hu, Jianbin ^{[8
,9
]}

Li, Yuanfeng ^{[1
,2
]}

Cai, Li ^{[1
,2
]}

Liu, Xiaoqi ^{[1
,2
]}

Lu, Fang ^{[1
,2
]}

Liao, Shihuang ^{[8
,9
]}

Chen, Bin ^{[8
,9
]}

He, Fei ^{[1
,2
]}

Gong, Bo ^{[1
,2
]}

Lin, He ^{[1
,2
]}

Ma, Shi ^{[1
,2
]}

Cheng, Jing ^{[1
,2
]}

Zhang, Jie ^{[10
]}

Chen, Yiye ^{[4
]}

Zhao, Fuxin ^{[3
]}

Yang, Xian ^{[11
]}

Chen, Yuhong ^{[12
,13
]}

Yang, Charles ^{[14
]}

Lam, Dennis Shun Chiu ^{[6
]}

Li, Xi ^{[1
,2
]}

Shi, Fanjun ^{[3
]}

Wu, Zhengzheng ^{[8
,9
]}

Lin, Ying ^{[1
,2
]}

Yang, Jiyun ^{[1
,2
]}

Li, Shiqiang ^{[5
]}

Ren, Yunqing ^{[7
]}

Xue, Anquan ^{[3
]}

Fan, Yingchuan ^{[8
,9
]}

Li, Dean ^{[15
]}

Pang, Chi Pui ^{[6
]}

Zhang, Xuejun ^{[7
]}

Yang, Zhenglin ^{[1
,2
]}

机构：

[1] Sichuan Prov Peoples Hosp, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu 610072, Sichuan, Peoples R China

[2] Sichuan Acad Med Sci, Inst Lab Med, Chengdu 610072, Sichuan, Peoples R China

[3] Wenzhou Med Coll, Sch Optometry & Ophthalmol, Wenzhou 325035, Zhejiang, Peoples R China

[4] Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Ophthalmol, Shanghai 200092, Peoples R China

[5] Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China

[6] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Kowloon, Hong Kong, Peoples R China

[7] Anhui Med Univ, Minist Educ, China Key Lab Dermatol, Hefei 230032, Anhui, Peoples R China

[8] Sichuan Acad Med Sci, Dept Ophthalmol, Chengdu 610072, Anhui, Peoples R China

[9] Sichuan Prov Peoples Hosp, Chengdu 610072, Anhui, Peoples R China

[10] Shiji Eye Hosp, Chengdu 610016, Anhui, Peoples R China

[11] Qingdao Univ, Affiliated Hosp, Coll Med, Dept Ophthalmol, Qingdao 266003, Peoples R China

[12] Fudan Univ, Dept Ophthalmol, Shanghai 200031, Peoples R China

[13] Fudan Univ, Visual Sci Eye & ENT Hosp, Shanghai Med Sch, Shanghai 200031, Peoples R China

[14] W High Sch, Salt Lake City, UT 84103 USA

[15] Univ Utah, Salt Lake City, UT 84132 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2011年 / 88卷 / 06期

关键词：

GENOME-WIDE ASSOCIATION; REFRACTIVE ERROR; SUSCEPTIBILITY LOCUS; PREVALENCE; HERITABILITY; POLYMORPHISM;

D O I：

10.1016/j.ajhg.2011.04.022

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：805 / 813

页数：9

共 29 条

[1] Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping [J].

Andrew, Toby ;

Maniatis, Nikolas ;

Carbonaro, Francis ;

Liew, S. H. Melissa ;

Lau, Winston ;

Spector, Tim D. ;

Hammond, Christopher J. .

PLOS GENETICS, 2008, 4 (10)

[2]

Banker A S, 2001, Ophthalmol Clin North Am, V14, P695, DOI 10.1016/S0896-1549(05)70268-6

[3] Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region [J].

Barrett, Jeffrey C. ;

Lee, James C. ;

Lees, Charles W. ;

Prescott, Natalie J. ;

Anderson, Carl A. ;

Phillips, Anne ;

Wesley, Emma ;

Parnell, Kirstie ;

Zhang, Hu ;

Drummond, Hazel ;

Nimmo, Elaine R. ;

Massey, Dunecan ;

Blaszczyk, Kasia ;

Elliott, Timothy ;

Cotterill, Lynn ;

Dallal, Helen ;

Lobo, Alan J. ;

Mowat, Craig ;

Sanderson, Jeremy D. ;

Jewell, Derek P. ;

Newman, William G. ;

Edwards, Cathryn ;

Ahmad, Tariq ;

Mansfield, John C. ;

Satsangi, Jack ;

Parkes, Miles ;

Mathew, Christopher G. ;

Donnelly, Peter ;

Peltonen, Leena ;

Blackwell, Jenefer M. ;

Bramon, Elvira ;

Brown, Matthew A. ;

Casas, Juan P. ;

Corvin, Aiden ;

Craddock, Nicholas ;

Deloukas, Panos ;

Duncanson, Audrey ;

Jankowski, Janusz ;

Markus, Hugh S. ;

McCarthy, Mark I. ;

Palmer, Colin N. A. ;

Plomin, Robert ;

Rautanen, Anna ;

Sawcer, Stephen J. ;

Samani, Nilesh ;

Trembath, Richard C. ;

Viswanathan, Ananth C. ;

Wood, Nicholas ;

Spencer, Chris C. A. ;

Bellenguez, Celine .

NATURE GENETICS, 2009, 41 (12) :1330-U99

[4] BRCC2, a novel BH3-like domain-containing protein, induces apoptosis in a caspase-dependent manner [J].

Broustas, CG ;

Gokhale, PC ;

Rahman, A ;

Dritschilo, A ;

Ahmad, I ;

Kasid, U .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (25) :26780-26788

[5] Cloning, expression, and chromosomal assignment of the human mitochondrial intermediate peptidase gene (MIPEP) [J].

Chew, A ;

Buck, EA ;

Peretz, S ;

Sirugo, G ;

Rinaldo, P ;

Isaya, G .

GENOMICS, 1997, 40 (03) :493-496

[6] HTRA1 promoter polymorphism in wet age-related macular degeneration [J].

DeWan, Andrew ;

Liu, Mugen ;

Hartman, Stephen ;

Zhang, Samuel Shao-Min ;

Liu, David T. L. ;

Zhao, Connie ;

Tam, Pancy O. S. ;

Chan, Wai Man ;

Lam, Dennis S. C. ;

Snyder, Michael ;

Barnstable, Colin ;

Pang, Chi Pui ;

Hoh, Josephine .

SCIENCE, 2006, 314 (5801) :989-992

[7] Heritability of refractive error and ocular biometrics: The Genes in Myopia (GEM) Twin Study [J].

Dirani, Mohamed ;

Chamberlain, Matthew ;

Shekar, Sri N. ;

Islam, Amirul F. M. ;

Garoufalis, Pam ;

Chen, Christine Y. ;

Guymer, Robyn H. ;

Baird, Paul N. .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (11) :4756-4761

[8]

HAYASHI H, 2011, INVEST OPHTHALMOL VI

[9] Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration:: a genetic model for age-related macular degeneration [J].

Hayward, C ;

Shu, XH ;

Lennon, A ;

Barran, P ;

Zareparsi, S ;

Sawyer, L ;

Hendry, G ;

Dhillon, B ;

Milam, AH ;

Luthert, PJ ;

Swaroop, A ;

Hastie, ND ;

Jacobson, SG ;

Wright, AF .

HUMAN MOLECULAR GENETICS, 2003, 12 (20) :2657-2667

[10] Prevalence of Myopia in Urban and Rural Children in Mainland China [J].

He, Mingguang ;

Zheng, Yingfeng ;

Xiang, Fan .

OPTOMETRY AND VISION SCIENCE, 2009, 86 (01) :40-44

← 1 2 3 →