A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25

被引：170

作者：

Hysi, Pirro G. ^{[1
]}

Young, Terri L. ^{[2
]}

Mackey, David A. ^{[3
,4
]}

Andrew, Toby ^{[1
]}

Fernandez-Medarde, Alberto ^{[5
]}

Solouki, Abbas M. ^{[6
,7
]}

Hewitt, Alex W. ^{[4
]}

Macgregor, Stuart ^{[8
]}

Vingerling, Johannes R. ^{[6
,7
]}

Li, Yi-Ju ^{[2
]}

Ikram, M. Kamran ^{[7
]}

Fai, Lee Yiu ^{[9
]}

Sham, Pak C. ^{[9
]}

Manyes, Lara ^{[5
]}

Porteros, Angel ^{[5
]}

Lopes, Margarida C. ^{[1
]}

Carbonaro, Francis ^{[1
]}

Fahy, Samantha J. ^{[1
]}

Martin, Nicholas G. ^{[8
]}

van Duijn, Cornelia M. ^{[7
]}

Spector, Timothy D. ^{[1
]}

Rahi, Jugnoo S. ^{[10
]}

Santos, Eugenio ^{[5
]}

Klaver, Caroline C. W. ^{[6
,7
]}

Hammond, Christopher J. ^{[1
]}

机构：

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

[2] Duke Univ, Ctr Human Genet, Durham, NC USA

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

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

[5] Univ Salamanca, CIC IBMCC CSIC USAL, E-37008 Salamanca, Spain

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

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

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

[9] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China

[10] UCL, Inst Child Hlth, Med Res Council Ctr Epidemiol Child Hlth, London, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 10期

基金：

英国医学研究理事会; 英国惠康基金; 美国国家卫生研究院;

关键词：

VISUAL IMPAIRMENT; UNITED-STATES; EYE GROWTH; PREVALENCE; RASGRF1; TRANSMISSION; HOMEOSTASIS; BLINDNESS;

D O I：

10.1038/ng.664

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Myopia and hyperopia are at opposite ends of the continuum of refraction, the measure of the eye's ability to focus light, which is an important cause of visual impairment (when aberrant) and is a highly heritable trait. We conducted a genome-wide association study for refractive error in 4,270 individuals from the TwinsUK cohort. We identified SNPs on 15q25 associated with refractive error (rs8027411, P = 7.91 x 10(-8)). We replicated this association in six adult cohorts of European ancestry with a combined 13,414 individuals (combined P = 2.07 x 10(-9)). This locus overlaps the transcription initiation site of RASGRF1, which is highly expressed in neurons and retina and has previously been implicated in retinal function and memory consolidation. Rasgrf1(-/-) mice show a heavier average crystalline lens (P = 0.001). The identification of a susceptibility locus for refractive error on 15q25 will be important in characterizing the molecular mechanism responsible for the most common cause of visual impairment.

引用

页码：902 / +

页数：5

共 29 条

[1] Causes of blindness and visual impairment in the West of Scotland [J].

Bamashmus, MA ;

Matlhaga, B ;

Dutton, GN .

EYE, 2004, 18 (03) :257-261

[2] A role for the Ras signalling pathway in synaptic transmission and long-term memory [J].

Brambilla, R ;

Gnesutta, N ;

Minichiello, L ;

White, G ;

Roylance, AJ ;

Herron, CE ;

Ramsey, M ;

Wolfer, DP ;

Cestari, V ;

RossiArnaud, C ;

Grant, SGN ;

Chapman, PF ;

Lipp, HP ;

Sturani, E ;

Klein, R .

NATURE, 1997, 390 (6657) :281-286

[3] Prevalence and causes of visual impairment and blindness among 9980 Scandinavian adults - The Copenhagen City Eye Study [J].

Buch, H ;

Vinding, T ;

la Cour, M ;

Appleyard, M ;

Jensen, GB ;

Nielsen, NV .

OPHTHALMOLOGY, 2004, 111 (01) :53-61

[4] Structural characterization of Rasgrf1 and a novel linked imprinted locus [J].

de la Puente, A ;

Hall, J ;

Wu, YZ ;

Leone, G ;

Peters, J ;

Yoon, BJ ;

Soloway, P ;

Plass, C .

GENE, 2002, 291 (1-2) :287-297

[5] Ras-GRF1 signaling is required for normal β-cell development and glucose homeostasis [J].

de Mora, JF ;

Esteban, LM ;

Burks, DJ ;

Núñez, A ;

Garcés, C ;

García-Barrado, MJ ;

Iglesias-Osma, MC ;

Moratinos, J ;

Ward, JM ;

Santos, E .

EMBO JOURNAL, 2003, 22 (12) :3039-3049

[6] Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina [J].

Deans, MR ;

Volgyi, B ;

Goodenough, DA ;

Bloomfield, SA ;

Paul, DL .

NEURON, 2002, 36 (04) :703-712

[7] Causes of visual impairment in people aged 75 years and older in Britain: an add-on study to the MRC Trial of Assessment and Management of Older People in the Community [J].

Evans, JR ;

Fletcher, AE ;

Wormald, RPL .

BRITISH JOURNAL OF OPHTHALMOLOGY, 2004, 88 (03) :365-370

[8] RasGRF1 disruption causes retinal photoreception defects and associated transcriptomic alterations [J].

Fernandez-Medarde, Alberto ;

Barhoum, Rima ;

Riquelme, Raquel ;

Porteros, Angel ;

Nunez, Alejandro ;

de Luis, Alberto ;

de las Rivas, Javier ;

de la Villa, Pedro ;

Varela-Nieto, Isabel ;

Santos, Eugenio .

JOURNAL OF NEUROCHEMISTRY, 2009, 110 (02) :641-652

[9] Estimating Heritability and Shared Environmental Effects for Refractive Error in Twin and Family Studies [J].

Lopes, Margarida C. ;

Andrew, Toby ;

Carbonaro, Francis ;

Spector, Tim D. ;

Hammond, Christopher J. .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2009, 50 (01) :126-131

[10] Phosphorylation-dependent activation of the Ras-GRF/CDC25(Mm) exchange factor by muscarinic receptors and G-protein beta gamma subunits [J].

Mattingly, RR ;

Macara, IG .

NATURE, 1996, 382 (6588) :268-272

← 1 2 3 →