Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia

被引：246

作者：

Hysi, Pirro G. ^{[1
,2
,3
]}

Choquet, Helene ^{[4
]}

Khawaja, Anthony P. ^{[5
,6
,7
]}

Wojciechowski, Robert ^{[8
,9
]}

Tedja, Milly S. ^{[10
,11
]}

Yin, Jie ^{[4
]}

Simcoe, Mark J. ^{[2
]}

Patasova, Karina ^{[1
]}

Mahroo, Omar A. ^{[1
,5
,6
]}

Thai, Khanh K. ^{[4
]}

Cumberland, Phillippa M. ^{[3
,12
]}

Melles, Ronald B. ^{[13
]}

Verhoeven, Virginie J. M. ^{[10
,11
,14
]}

Vitart, Veronique ^{[15
]}

Segre, Ayellet ^{[16
]}

Stone, Richard A. ^{[17
]}

Wareham, Nick ^{[7
]}

Hewitt, Alex W. ^{[18
]}

Mackey, David A. ^{[18
,19
]}

Klaver, Caroline C. W. ^{[10
,11
,20
,21
]}

MacGregor, Stuart ^{[22
]}

Khaw, Peng T. ^{[5
,6
]}

Foster, Paul J. ^{[5
,6
,23
]}

Guggenheim, Jeremy A. ^{[24
]}

Rahi, Jugnoo S. ^{[3
,5
,6
,12
,25
,26
]}

Jorgenson, Eric ^{[4
]}

Hammond, Christopher J. ^{[1
,2
]}

机构：

[1] Kings Coll London, Sch Life Course Sci, Sect Ophthalmol, London, England

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

[3] UCL, UCL Great Ormond St Inst Child Hlth, London, England

[4] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA

[5] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England

[6] UCL Inst Ophthalmol, London, England

[7] Univ Cambridge, Sch Clin Med, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England

[8] Johns Hopkins Univ, Dept Biophys, Baltimore, MD USA

[9] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA

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

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

[12] UCL, UCL Great Ormond St Inst Child Hlth, Ulverscroft Vis Res Grp, London, England

[13] Kaiser Permanente Northern Calif, Dept Ophthalmol, Redwood City, CA USA

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

[15] Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[16] Harvard Med Sch, Massachusetts Eye & Ear, Dept Ophthalmol, Boston, MA 02115 USA

[17] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA

[18] Royal Hobart Hosp, Dept Ophthalmol, Hobart, Tas, Australia

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

[20] Radboud Univ Nijmegen, Dept Ophthalmol, Med Ctr, Rotterdam, Netherlands

[21] Inst Mol & Clin Ophthalmol Basel, Basel, Switzerland

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

[23] UCL Inst Ophthalmol, Div Genet & Epidemiol, London, England

[24] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff, Wales

[25] Great Ormond St Hosp NHS Fdn Trust, Biomed Res Ctr, Dept Ophthalmol, London, England

[26] Great Ormond St Hosp NHS Fdn Trust, Biomed Res Ctr, NIHR, London, England

来源：

NATURE GENETICS | 2020年 / 52卷 / 04期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; EPIDEMIOLOGY RESEARCH; QUALITY-CONTROL; ADULT HEALTH; SUSCEPTIBILITY; HERITABILITY; MULTIPLE; ALBINISM; VSX1; MUTATIONS;

D O I：

10.1038/s41588-020-0599-0

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future. Meta-analysis of genome-wide association studies of 542,934 individuals identifies 336 novel loci associated with refractive error and implicates eye development, circadian rhythm and pigmentation pathways in controlling myopia.

引用

页码：401 / +

页数：20

共 79 条

[1] Null Mutations in LTBP2 Cause Primary Congenital Glaucoma [J].

Ali, Manir ;

McKibbin, Martin ;

Booth, Adam ;

Parry, David A. ;

Jain, Payal ;

Riazuddin, S. Amer ;

Hejtmancik, J. Fielding ;

Khan, Shaheen N. ;

Firasat, Sabika ;

Shires, Mike ;

Gilmour, David F. ;

Towns, Katherine ;

Murphy, Anna-Louise ;

Azmanov, Dimitar ;

Tournev, Ivailo ;

Cherninkova, Sylvia ;

Jafri, Hussain ;

Raashid, Yasmin ;

Toomes, Carmel ;

Craig, Jamie ;

Mackey, David A. ;

Kalaydjieva, Luba ;

Riazuddin, Sheikh ;

Inglehearn, Chris F. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (05) :664-671

[2]

[Anonymous], 2008, GLOB BURD DIS 2004 U

[3]

[Anonymous], 2015, CURRENT OPHTHALMOLOG, DOI [DOI 10.1007/S40135-015-0083-7, DOI 10.1136/bjophthalmol-2011-300072]

[4] TRPM1 Is Mutated in Patients with Autosomal-Recessive Complete Congenital Stationary Night Blindness [J].

Audo, Isabelle ;

Kohl, Susanne ;

Leroy, Bart P. ;

Munier, Francis L. ;

Guillonneau, Xavier ;

Mohand-Said, Saddek ;

Bujakowska, Kinga ;

Nandrot, Emeline F. ;

Lorenz, Birgit ;

Preising, Markus ;

Kellner, Ulrich ;

Renner, Agnes B. ;

Bernd, Antje ;

Antonio, Aline ;

Moskova-Doumanova, Veselina ;

Lancelot, Marie-Elise ;

Poloschek, Charlotte M. ;

Drumare, Isabelle ;

Defoort-Dhellemmes, Sabine ;

Wissinger, Bernd ;

Leveillard, Thierry ;

Hamel, Christian P. ;

Schorderet, Daniel F. ;

De Baere, Elfride ;

Berger, Wolfgang ;

Jacobson, Samuel G. ;

Zrenner, Eberhart ;

Sahel, Jose-Alain ;

Bhattacharya, Shomi S. ;

Zeitz, Christina .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (05) :720-729

[5] Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort [J].

Banda, Yambazi ;

Kvale, Mark N. ;

Hoffmann, Thomas J. ;

Hesselson, Stephanie E. ;

Ranatunga, Dilrini ;

Tang, Hua ;

Sabatti, Chiara ;

Croen, Lisa A. ;

Dispensa, Brad P. ;

Henderson, Mary ;

Iribarren, Carlos ;

Jorgenson, Eric ;

Kushi, Lawrence H. ;

Ludwig, Dana ;

Olberg, Diane ;

Quesenberry, Charles P., Jr. ;

Rowell, Sarah ;

Sadler, Marianne ;

Sakoda, Lori C. ;

Sciortino, Stanley ;

Shen, Ling ;

Smethurst, David ;

Somkin, Carol P. ;

Van Den Eeden, Stephen K. ;

Walter, Lawrence ;

Whitmer, Rachel A. ;

Kwok, Pui-Yan ;

Schaefer, Catherine ;

Risch, Neil .

GENETICS, 2015, 200 (04) :1285-+

[6] Childhood intelligence is heritable, highly polygenic and associated with FNBP1L [J].

Benyamin, B. ;

St Pourcain, B. ;

Davis, O. S. ;

Davies, G. ;

Hansell, N. K. ;

Brion, M-J A. ;

Kirkpatrick, R. M. ;

Cents, R. A. M. ;

Franic, S. ;

Miller, M. B. ;

Haworth, C. M. A. ;

Meaburn, E. ;

Price, T. S. ;

Evans, D. M. ;

Timpson, N. ;

Kemp, J. ;

Ring, S. ;

McArdle, W. ;

Medland, S. E. ;

Yang, J. ;

Harris, S. E. ;

Liewald, D. C. ;

Scheet, P. ;

Xiao, X. ;

Hudziak, J. J. ;

de Geus, E. J. C. ;

Jaddoe, V. W. V. ;

Starr, J. M. ;

Verhulst, F. C. ;

Pennell, C. ;

Tiemeier, H. ;

Iacono, W. G. ;

Palmer, L. J. ;

Montgomery, G. W. ;

Martin, N. G. ;

Boomsma, D. I. ;

Posthuma, D. ;

McGue, M. ;

Wright, M. J. ;

Smith, G. Davey ;

Deary, I. J. ;

Plomin, R. ;

Visscher, P. M. .

MOLECULAR PSYCHIATRY, 2014, 19 (02) :253-258

[7] An atlas of genetic correlations across human diseases and traits [J].

Bulik-Sullivan, Brendan ;

Finucane, Hilary K. ;

Anttila, Verneri ;

Gusev, Alexander ;

Day, Felix R. ;

Loh, Po-Ru ;

Duncan, Laramie ;

Perry, John R. B. ;

Patterson, Nick ;

Robinson, Elise B. ;

Daly, Mark J. ;

Price, Alkes L. ;

Neale, Benjamin M. .

NATURE GENETICS, 2015, 47 (11) :1236-+

[8] LD Score regression distinguishes confounding from polygenicity in genome-wide association studies [J].

Bulik-Sullivan, Brendan K. ;

Loh, Po-Ru ;

Finucane, Hilary K. ;

Ripke, Stephan ;

Yang, Jian ;

Patterson, Nick ;

Daly, Mark J. ;

Price, Alkes L. ;

Neale, Benjamin M. .

NATURE GENETICS, 2015, 47 (03) :291-+

[9] The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019 [J].

Buniello, Annalisa ;

MacArthur, Jacqueline A. L. ;

Cerezo, Maria ;

Harris, Laura W. ;

Hayhurst, James ;

Malangone, Cinzia ;

McMahon, Aoife ;

Morales, Joannella ;

Mountjoy, Edward ;

Sollis, Elliot ;

Suveges, Daniel ;

Vrousgou, Olga ;

Whetzel, Patricia L. ;

Amode, Ridwan ;

Guillen, Jose A. ;

Riat, Harpreet S. ;

Trevanion, Stephen J. ;

Hall, Peggy ;

Junkins, Heather ;

Flicek, Paul ;

Burdett, Tony ;

Hindorff, Lucia A. ;

Cunningham, Fiona ;

Parkinson, Helen .

NUCLEIC ACIDS RESEARCH, 2019, 47 (D1) :D1005-D1012

[10] The α7β1 integrin in muscle development and disease [J].

Burkin, DJ ;

Kaufman, SJ .

CELL AND TISSUE RESEARCH, 1999, 296 (01) :183-190

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