Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations

被引：39

作者：

Bonnemaijer, Pieter W. M. ^{[1
,2
,3
]}

Iglesias, Adriana I. ^{[1
,2
,4
]}

Nadkarni, Girish N. ^{[5
,6
]}

Sanyiwa, Anna J. ^{[7
]}

Hassan, Hassan G. ^{[8
]}

Cook, Colin ^{[9
]}

Simcoe, Mark ^{[10
]}

Taylor, Kent D. ^{[11
]}

Schurmann, Claudia ^{[5
]}

Belbin, Gillian M. ^{[5
,12
]}

Kenny, Eimear E. ^{[5
,12
,13
,14
]}

Bottinger, Erwin P. ^{[5
]}

van de Laar, Suzanne ^{[15
]}

Wiliams, Susan E. I. ^{[16
]}

Akafo, Stephen K. ^{[17
]}

Ashaye, Adeyinka O. ^{[18
]}

Zangwill, Linda M. ^{[19
]}

Girkin, Christopher A. ^{[20
]}

Ng, Maggie C. Y. ^{[21
]}

Rotter, Jerome I.

Weinreb, Robert N. ^{[19
]}

Li, Zheng ^{[22
]}

Allingham, R. Rand ^{[23
]}

Nag, Abhishek ^{[10
]}

Hysi, Pirro G. ^{[10
]}

Meester-Smoor, Magda A. ^{[1
,2
]}

Wiggs, Janey L. ^{[24
]}

Hauser, Michael A. ^{[25
]}

Hammond, Christopher J. ^{[10
]}

Lemij, Hans G. ^{[26
]}

Loos, Ruth J. F. ^{[5
,27
]}

van Duijn, Cornelia M. ^{[2
]}

Thiadens, Alberta A. H. J. ^{[1
,2
]}

Klaver, Caroline C. W. ^{[1
,2
,28
]}

机构：

[1] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands

[2] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[3] Rotterdam Eye Hosp, Rotterdam, Netherlands

[4] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[5] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Div Nephrol, Dept Med, New York, NY 10029 USA

[7] Muhimbili Natl Hosp, Muhimbili Univ Hlth & Allied Sci, Dept Ophthalmol, Dar Es Salaam, Tanzania

[8] CCBRT Hosp, Dept Ophthalmol, Dar Es Salaam, Tanzania

[9] Univ Cape Town, Div Ophthalmol, Cape Town, South Africa

[10] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

[11] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90509 USA

[12] Icahn Sch Med Mt Sinai, Genet & Genom Sci, New York, NY USA

[13] Icahn Sch Med Mt Sinai, Ctr Stat Genet, New York, NY USA

[14] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY USA

[15] Univ Med Ctr, Dept Ophthalmol, Utrecht, Netherlands

[16] Univ Witwatersrand, Dept Neurosci, Div Ophthalmol, Johannesburg, South Africa

[17] Univ Ghana, Sch Med & Dent, Dept Surg, Unit Ophthalmol, Accra, Ghana

[18] Univ Ibadan, Dept Ophthalmol, Coll Med, Ibadan, Nigeria

[19] Univ Calif San Diego, Shiley Eye Inst, Dept Ophthalmol, Hamilton Glaucoma Ctr, La Jolla, CA USA

[20] Univ Alabama Birmingham, Dept Ophthalmol, Med Sch Birmingham, Birmingham, AL 35294 USA

[21] Wake Forest Sch Med, Ctr Diabet Res, Dept Biochem, Winston Salem, NC USA

[22] Genome Inst Singapore, Singapore, Singapore

[23] Duke Univ, Dept Ophthalmol, Durham, NC USA

[24] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA

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

[26] Rotterdam Eye Hosp, Glaucoma Serv, Rotterdam, Netherlands

[27] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA

[28] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, Nijmegen, Netherlands

来源：

HUMAN GENETICS | 2018年 / 137卷 / 10期

关键词：

COMMON VARIANTS; SUSCEPTIBILITY LOCI; METAANALYSIS; IMPUTATION; GENE; PREVALENCE; PLINK; RISK;

D O I：

10.1007/s00439-018-1943-7

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 complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P=0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P=4.79x10(-5)). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P=3.75x10(-8)), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.

引用

页码：847 / 862

页数：16

共 45 条

[11] Next-generation genotype imputation service and methods [J].

Das, Sayantan ;

Forer, Lukas ;

Schoenherr, Sebastian ;

Sidore, Carlo ;

Locke, Adam E. ;

Kwong, Alan ;

Vrieze, Scott I. ;

Chew, Emily Y. ;

Levy, Shawn ;

McGue, Matt ;

Schlessinger, David ;

Stambolian, Dwight ;

Loh, Po-Ru ;

Iacono, William G. ;

Swaroop, Anand ;

Scott, Laura J. ;

Cucca, Francesco ;

Kronenberg, Florian ;

Boehnke, Michael ;

Abecasis, Goncalo R. ;

Fuchsberger, Christian .

NATURE GENETICS, 2016, 48 (10) :1284-1287

[12] BIAS REDUCTION OF MAXIMUM-LIKELIHOOD-ESTIMATES [J].

FIRTH, D .

BIOMETRIKA, 1993, 80 (01) :27-38

[13] The definition and classification of glaucoma in prevalence surveys [J].

Foster, PJ ;

Buhrmann, R ;

Quigley, HA ;

Johnson, GJ .

BRITISH JOURNAL OF OPHTHALMOLOGY, 2002, 86 (02) :238-242

[14] The structure of haplotype blocks in the human genome [J].

Gabriel, SB ;

Schaffner, SF ;

Nguyen, H ;

Moore, JM ;

Roy, J ;

Blumenstiel, B ;

Higgins, J ;

DeFelice, M ;

Lochner, A ;

Faggart, M ;

Liu-Cordero, SN ;

Rotimi, C ;

Adeyemo, A ;

Cooper, R ;

Ward, R ;

Lander, ES ;

Daly, MJ ;

Altshuler, D .

SCIENCE, 2002, 296 (5576) :2225-2229

[15] Random-Effects Model Aimed at Discovering Associations in Meta-Analysis of Genome-wide Association Studies [J].

Han, Buhm ;

Eskin, Eleazar .

AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 88 (05) :586-598

[16] TGF-β2-Induced Invadosomes in Human Trabecular Meshwork Cells [J].

Han, Hong ;

Kampik, Daniel ;

Grehn, Franz ;

Schlunck, Guenther .

PLOS ONE, 2013, 8 (08)

[17] Genome-wide association and admixture analysis of glaucoma in the Women's Health Initiative [J].

Hoffmann, Thomas J. ;

Tang, Hua ;

Thornton, Timothy A. ;

Caan, Bette ;

Haan, Mary ;

Millen, Amy E. ;

Thomas, Fridtjof ;

Risch, Neil .

HUMAN MOLECULAR GENETICS, 2014, 23 (24) :6634-6643

[18] A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies [J].

Howie, Bryan N. ;

Donnelly, Peter ;

Marchini, Jonathan .

PLOS GENETICS, 2009, 5 (06)

[19] Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma [J].

Hysi, Pirro G. ;

Cheng, Ching-Yu ;

Springelkamp, Henriet ;

Macgregor, Stuart ;

Bailey, Jessica N. Cooke ;

Wojciechowski, Robert ;

Vitart, Veronique ;

Nag, Abhishek ;

Hewitt, Alex W. ;

Hohn, Rene ;

Venturini, Cristina ;

Mirshahi, Alireza ;

Ramdas, Wishal D. ;

Thorleifsson, Gudmar ;

Vithana, Eranga ;

Khor, Chiea-Chuen ;

Stefansson, Arni B. ;

Liao, Jiemin ;

Haines, Jonathan L. ;

Amin, Najaf ;

Wang, Ya Xing ;

Wild, Philipp S. ;

Ozel, Ayse B. ;

Li, Jun Z. ;

Fleck, Brian W. ;

Zeller, Tanja ;

Staffieri, Sandra E. ;

Teo, Yik-Ying ;

Cuellar-Partida, Gabriel ;

Luo, Xiaoyan ;

Allingham, R. Rand ;

Richards, Julia E. ;

Senft, Andrea ;

Karssen, Lennart C. ;

Zheng, Yingfeng ;

Bellenguez, Celine ;

Xu, Liang ;

Iglesias, Adriana I. ;

Wilson, James F. ;

Kang, Jae H. ;

van Leeuwen, Elisabeth M. ;

Jonsson, Vesteinn ;

Thorsteinsdottir, Unnur ;

Despriet, Dominiek D. G. ;

Ennis, Sarah ;

Moroi, Sayoko E. ;

Martin, Nicholas G. ;

Jansonius, Nomdo M. ;

Yazar, Seyhan ;

Tai, E-Shyong .

NATURE GENETICS, 2014, 46 (10) :1126-1130

[20] Integrative analysis of 111 reference human epigenomes [J].

Kundaje, Anshul ;

Meuleman, Wouter ;

Ernst, Jason ;

Bilenky, Misha ;

Yen, Angela ;

Heravi-Moussavi, Alireza ;

Kheradpour, Pouya ;

Zhang, Zhizhuo ;

Wang, Jianrong ;

Ziller, Michael J. ;

Amin, Viren ;

Whitaker, John W. ;

Schultz, Matthew D. ;

Ward, Lucas D. ;

Sarkar, Abhishek ;

Quon, Gerald ;

Sandstrom, Richard S. ;

Eaton, Matthew L. ;

Wu, Yi-Chieh ;

Pfenning, Andreas R. ;

Wang, Xinchen ;

Claussnitzer, Melina ;

Liu, Yaping ;

Coarfa, Cristian ;

Harris, R. Alan ;

Shoresh, Noam ;

Epstein, Charles B. ;

Gjoneska, Elizabeta ;

Leung, Danny ;

Xie, Wei ;

Hawkins, R. David ;

Lister, Ryan ;

Hong, Chibo ;

Gascard, Philippe ;

Mungall, Andrew J. ;

Moore, Richard ;

Chuah, Eric ;

Tam, Angela ;

Canfield, Theresa K. ;

Hansen, R. Scott ;

Kaul, Rajinder ;

Sabo, Peter J. ;

Bansal, Mukul S. ;

Carles, Annaick ;

Dixon, Jesse R. ;

Farh, Kai-How ;

Feizi, Soheil ;

Karlic, Rosa ;

Kim, Ah-Ram ;

Kulkarni, Ashwinikumar .

NATURE, 2015, 518 (7539) :317-330

← 1 2 3 4 5 →