Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

被引：160

作者：

Gharahkhani, Puya ^{[1
]}

Burdon, Kathryn P. ^{[2
,3
,4
]}

Fogarty, Rhys ^{[2
]}

Sharma, Shiwani ^{[2
]}

Hewitt, Alex W. ^{[4
]}

Martin, Sarah ^{[2
]}

Law, Matthew H. ^{[1
]}

Cremin, Katie ^{[5
]}

Bailey, Jessica N. Cooke ^{[6
,7
]}

Loomis, Stephanie J. ^{[8
,9
]}

Pasquale, Louis R. ^{[8
,9
,10
]}

Haines, Jonathan L. ^{[6
,7
]}

Hauser, Michael A. ^{[11
,12
]}

Viswanathan, Ananth C. ^{[13
,14
]}

McGuffin, Peter ^{[15
]}

Topouzis, Fotis ^{[16
]}

Foster, Paul J. ^{[13
,14
]}

Graham, Stuart L. ^{[17
]}

Casson, Robert J. ^{[18
]}

Chehade, Mark ^{[18
]}

White, Andrew J. ^{[19
]}

Zhou, Tiger ^{[2
]}

Souzeau, Emmanuelle ^{[2
]}

Landers, John ^{[2
]}

Fitzgerald, Jude T. ^{[2
]}

Klebe, Sonja ^{[20
]}

Ruddle, Jonathan B. ^{[4
]}

Goldberg, Ivan ^{[21
]}

Healey, Paul R. ^{[19
]}

Mills, Richard A. ^{[2
]}

Wang, Jie Jin ^{[19
]}

Montgomery, Grant W. ^{[1
]}

Martin, Nicholas G. ^{[1
]}

Radford-Smith, Graham ^{[22
]}

Whiteman, David C. ^{[1
]}

Brown, Matthew A. ^{[5
]}

Wiggs, Janey L. ^{[8
,9
]}

Mackey, David A. ^{[3
,23
]}

Mitchell, Paul

MacGregor, Stuart ^{[1
]}

Craig, Jamie E. ^{[2
,24
]}

机构：

[1] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[2] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia

[3] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia

[4] Univ Melbourne, Royal Victorian Eye & Ear Hosp, CERA, Melbourne, Vic, Australia

[5] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia

[6] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA

[7] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA

[8] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA

[9] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA

[10] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA

[11] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA

[12] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[13] Moorfields Eye Hosp Natl Hlth Serv NHS Fdn Trus, Biomed Res Ctr, NIHR, London, England

[14] UCL, Inst Ophthalmol, London, England

[15] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, MRC, London, England

[16] Aristotle Univ Thessaloniki, Sch Med, AHEPA Hosp, Dept Ophthalmol, Thessaloniki, Greece

[17] Macquarie Univ, Sydney, NSW 2109, Australia

[18] Univ Adelaide, South Australian Inst Ophthalmol, Adelaide, SA, Australia

[19] Univ Sydney, Westmead Millennium Inst, Ctr Vis Res, Westmead, NSW 2145, Australia

[20] Flinders Univ S Australia, Flinders Med Ctr, Dept Anat Pathol, Adelaide, SA 5001, Australia

[21] Univ Sydney, Dept Ophthalmol, Sydney, NSW 2006, Australia

[22] Univ Queensland, Sch Med, Brisbane, Qld, Australia

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

[24] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia

来源：

NATURE GENETICS | 2014年 / 46卷 / 10期

基金：

英国惠康基金; 澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院; 澳大利亚研究理事会; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; BIOLOGICAL FUNCTION; AQUEOUS-HUMOR; GENE; IDENTIFICATION; AFAP-110; ABILITY;

D O I：

10.1038/ng.3079

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 x 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 x 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 x 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.

引用

页码：1120 / 1125

页数：6

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