Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

被引：339

作者：

Burdon, Kathryn P. ^{[1
]}

Macgregor, Stuart ^{[2
]}

Hewitt, Alex W. ^{[1
,3
]}

Sharma, Shiwani ^{[1
]}

Chidlow, Glyn ^{[4
,5
]}

Mills, Richard A. ^{[1
]}

Danoy, Patrick ^{[6
]}

Casson, Robert ^{[4
,5
]}

Viswanathan, Ananth C. ^{[7
]}

Liu, Jimmy Z. ^{[2
]}

Landers, John ^{[1
]}

Henders, Anjali K. ^{[2
]}

Wood, John ^{[4
,5
]}

Souzeau, Emmanuelle ^{[1
]}

Crawford, April ^{[1
]}

Leo, Paul ^{[6
]}

Wang, Jie Jin ^{[3
,8
,9
]}

Rochtchina, Elena ^{[8
,9
]}

Nyholt, Dale R. ^{[2
]}

Martin, Nicholas G. ^{[2
]}

Montgomery, Grant W. ^{[2
]}

Mitchell, Paul ^{[8
,9
]}

Brown, Matthew A. ^{[6
]}

Mackey, David A. ^{[3
,10
,11
]}

Craig, Jamie E. ^{[1
]}

机构：

[1] Flinders Univ S Australia, Dept Ophthalmol, Flinders Med Ctr, Adelaide, SA 5001, Australia

[2] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[3] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia

[4] Univ Adelaide, Adelaide, SA, Australia

[5] Hanson Inst, S Australian Inst Ophthalmol, Adelaide, SA, Australia

[6] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld, Australia

[7] Moorfields Eye Hosp, London, England

[8] Univ Sydney, Westmead Millennium Inst, Westmead, NSW 2145, Australia

[9] Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Westmead, NSW 2145, Australia

[10] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia

[11] Univ Tasmania, Discipline Med, Hobart, Tas, Australia

来源：

NATURE GENETICS | 2011年 / 43卷 / 06期

基金：

英国医学研究理事会; 澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

VISUALIZATION; GENOTYPE; FAMILY; ANRIL; GENE;

D O I：

10.1038/ng.824

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 x 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 x 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 x 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 x 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.

引用

页码：574 / U110

页数：7

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