Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma

被引：319

作者：

Thorleifsson, Gudmar ^{[1
]}

Walters, G. Bragi ^{[1
]}

Hewitt, Alex W. ^{[2
,3
]}

Masson, Gisli ^{[1
]}

Helgason, Agnar ^{[4
]}

DeWan, Andrew ^{[5
]}

Sigurdsson, Asgeir ^{[1
]}

Jonasdottir, Adalbjorg ^{[1
]}

Gudjonsson, Sigurjon A. ^{[1
]}

Magnusson, Kristinn P. ^{[6
]}

Stefansson, Hreinn ^{[1
]}

Lam, Dennis S. C.

Tam, Pancy O. S. ^{[7
]}

Gudmundsdottir, Gudrun J. ^{[8
,9
]}

Southgate, Laura ^{[10
]}

Burdon, Kathryn P. ^{[3
]}

Gottfredsdottir, Maria Soffia ^{[11
]}

Aldred, Micheala A. ^{[12
]}

Mitchell, Paul ^{[13
,14
]}

St Clair, David ^{[15
]}

Collier, David A. ^{[16
,17
]}

Tang, Nelson ^{[18
]}

Sveinsson, Orn ^{[19
]}

Macgregor, Stuart ^{[20
]}

Martin, Nicholas G. ^{[20
]}

Cree, Angela J. ^{[21
]}

Gibson, Jane ^{[22
]}

MacLeod, Alex ^{[23
]}

Jacob, Aby ^{[23
]}

Ennis, Sarah ^{[22
]}

Young, Terri L. ^{[24
]}

Chan, Juliana C. N. ^{[25
]}

Karwatowski, Wojciech S. S. ^{[26
]}

Hammond, Christopher J. ^{[27
]}

Thordarson, Kristjan ^{[28
]}

Zhang, Mingzhi ^{[29
,30
]}

Wadelius, Claes ^{[31
]}

Lotery, Andrew J. ^{[23
]}

Trembath, Richard C.

Pang, Chi Pui

Hoh, Josephine ^{[5
]}

Craig, Jamie E. ^{[3
]}

Kong, Augustine ^{[1
]}

Mackey, David A. ^{[32
,33
]}

Jonasson, Fridbert ^{[11
,34
]}

Thorsteinsdottir, Unnur ^{[34
]}

Stefansson, Kari ^{[1
,34
]}

机构：

[1] DeCODE genetics Inc, Reykjavik, Iceland

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

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

[4] Univ Iceland, Reykjavik, Iceland

[5] Yale Univ, Dept Epidemiol Publ Hlth, New Haven, CT USA

[6] Univ Akureyri, Dept Biotechnol, Akureyri, Iceland

[7] Chinese Univ Hong Kong, Dept Optometry & Visual Sci, Hong Kong, Hong Kong, Peoples R China

[8] Eye Clin, Akranes, Iceland

[9] Eye Clin Hamrahlid, Reykjavik, Iceland

[10] Guys Hosp, Sch Med, Dept Med & Mol Genet, Univ London Kings Coll, London SE1 9RT, England

[11] Natl Univ Hosp Reykjavik, Dept Ophthalmol, Reykjavik, Iceland

[12] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA

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

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

[15] Univ Aberdeen, Royal Cornhill Hosp, Dept Mental Hlth, Aberdeen, Scotland

[16] Kings Coll London, Inst Psychiat, Div Psychiat Med, London WC2R 2LS, England

[17] Sichuan Univ, W China Hosp, Dept Psychiat, Psychiatr Lab, Sichuan, Peoples R China

[18] Chinese Univ Hong Kong, Lab Genet Dis Susceptibil, Li Ka Shing Inst Hlth Sci, Fac Med, Hong Kong, Peoples R China

[19] Eye Clin, Reykjavik, Iceland

[20] Queensland Inst Med Res, Genet & Populat Hlth, Brisbane, Qld 4006, Australia

[21] Univ Southampton, Sch Med, Clin Neurosci Div, Southampton, Hants, England

[22] Univ Southampton, Sch Med, Div Human Genet, Genet Epidemiol & Bioinformat Grp, Southampton, Hants, England

[23] Southampton Univ Hosp Trust, Southampton Eye Unit, Southampton, Hants, England

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

[25] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China

[26] Univ Hosp Leicester, Dept Ophthalmol, Leicester, Leics, England

[27] Kings Coll London, Sch Med, Dept Twin Res & Genet Epidemiol, St Thomas Hosp, London WC2R 2LS, England

[28] Eye Clin, Reykjavik, Iceland

[29] Chinese Univ Hong Kong, Shantou, Peoples R China

[30] Shantou Univ, Joint Shantou Int Eye Ctr, Shantou, Peoples R China

[31] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden

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

[33] Univ Tasmania, Royal Hobart Hosp, 31Discipline Med, Hobart, Tas, Australia

[34] Univ Iceland, Fac Med, Reykjavik, Iceland

来源：

NATURE GENETICS | 2010年 / 42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; 英国医学研究理事会; 美国国家卫生研究院; 瑞典研究理事会;

关键词：

NITRIC-OXIDE SYNTHASE; TRABECULAR MESHWORK; GENE-EXPRESSION; CAVEOLAE; IDENTIFICATION; BIOLOGY;

D O I：

10.1038/ng.661

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[ A], odds ratio (OR) = 1.36, P = 5.0 x 10(-10)). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.

引用

页码：906 / +

页数：5

共 35 条

[1] The genetics of primary open-angle glaucoma: A review [J].

Allingham, R. Rand ;

Liu, Yutao ;

Rhee, Douglas J. .

EXPERIMENTAL EYE RESEARCH, 2009, 88 (04) :837-844

[2]

Berta AI, 2007, MOL VIS, V13, P881

[3] Gene expression in the trabecular meshwork and the influence of intraocular pressure [J].

Borrás, T .

PROGRESS IN RETINAL AND EYE RESEARCH, 2003, 22 (04) :435-463

[4] Cell biology of caveolae and caveolin [J].

Couet, J ;

Belanger, MM ;

Roussel, E ;

Drolet, MC .

ADVANCED DRUG DELIVERY REVIEWS, 2001, 49 (03) :223-235

[5] Genomic control for association studies [J].

Devlin, B ;

Roeder, K .

BIOMETRICS, 1999, 55 (04) :997-1004

[6] Genetics of gene expression and its effect on disease [J].

Emilsson, Valur ;

Thorleifsson, Gudmar ;

Zhang, Bin ;

Leonardson, Amy S. ;

Zink, Florian ;

Zhu, Jun ;

Carlson, Sonia ;

Helgason, Agnar ;

Walters, G. Bragi ;

Gunnarsdottir, Steinunn ;

Mouy, Magali ;

Steinthorsdottir, Valgerdur ;

Eiriksdottir, Gudrun H. ;

Bjornsdottir, Gyda ;

Reynisdottir, Inga ;

Gudbjartsson, Daniel ;

Helgadottir, Anna ;

Jonasdottir, Aslaug ;

Jonasdottir, Adalbjorg ;

Styrkarsdottir, Unnur ;

Gretarsdottir, Solveig ;

Magnusson, Kristinn P. ;

Stefansson, Hreinn ;

Fossdal, Ragnheidur ;

Kristjansson, Kristleifur ;

Gislason, Hjortur G. ;

Stefansson, Tryggvi ;

Leifsson, Bjorn G. ;

Thorsteinsdottir, Unnur ;

Lamb, John R. ;

Gulcher, Jeffrey R. ;

Reitman, Marc L. ;

Kong, Augustine ;

Schadt, Eric E. ;

Stefansson, Kari .

NATURE, 2008, 452 (7186) :423-U2

[7] Gene mapping for primary open angle glaucoma [J].

Fan, BJ ;

Wang, DY ;

Lam, DSC ;

Pang, CP .

CLINICAL BIOCHEMISTRY, 2006, 39 (03) :249-258

[8] A second generation human haplotype map of over 3.1 million SNPs [J].

Frazer, Kelly A. ;

Ballinger, Dennis G. ;

Cox, David R. ;

Hinds, David A. ;

Stuve, Laura L. ;

Gibbs, Richard A. ;

Belmont, John W. ;

Boudreau, Andrew ;

Hardenbol, Paul ;

Leal, Suzanne M. ;

Pasternak, Shiran ;

Wheeler, David A. ;

Willis, Thomas D. ;

Yu, Fuli ;

Yang, Huanming ;

Zeng, Changqing ;

Gao, Yang ;

Hu, Haoran ;

Hu, Weitao ;

Li, Chaohua ;

Lin, Wei ;

Liu, Siqi ;

Pan, Hao ;

Tang, Xiaoli ;

Wang, Jian ;

Wang, Wei ;

Yu, Jun ;

Zhang, Bo ;

Zhang, Qingrun ;

Zhao, Hongbin ;

Zhao, Hui ;

Zhou, Jun ;

Gabriel, Stacey B. ;

Barry, Rachel ;

Blumenstiel, Brendan ;

Camargo, Amy ;

Defelice, Matthew ;

Faggart, Maura ;

Goyette, Mary ;

Gupta, Supriya ;

Moore, Jamie ;

Nguyen, Huy ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Roy, Jessica ;

Stahl, Erich ;

Winchester, Ellen ;

Ziaugra, Liuda ;

Altshuler, David ;

Shen, Yan .

NATURE, 2007, 449 (7164) :851-U3

[9] Modulation of extracellular matrix turnover in the trabecular meshwork [J].

Fuchshofer, Rudolf ;

Tamm, Ernst R. .

EXPERIMENTAL EYE RESEARCH, 2009, 88 (04) :683-688

[10] Dissecting the interaction between nitric oxide synthase (NOS) and caveolin - Functional significance of the NOS caveolin binding domain in vivo [J].

GarciaCardena, G ;

Martasek, P ;

Masters, BSS ;

Skidd, PM ;

Couet, J ;

Li, SW ;

Lisanti, MP ;

Sessa, WC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (41) :25437-25440

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