Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2013 Mar;45(3):314-8.
doi: 10.1038/ng.2554. Epub 2013 Feb 10.

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Virginie J M Verhoeven  1 , Pirro G Hysi, Robert Wojciechowski, Qiao Fan, Jeremy A Guggenheim, René Höhn, Stuart MacGregor, Alex W Hewitt, Abhishek Nag, Ching-Yu Cheng, Ekaterina Yonova-Doing, Xin Zhou, M Kamran Ikram, Gabriëlle H S Buitendijk, George McMahon, John P Kemp, Beate St Pourcain, Claire L Simpson, Kari-Matti Mäkelä, Terho Lehtimäki, Mika Kähönen, Andrew D Paterson, S Mohsen Hosseini, Hoi Suen Wong, Liang Xu, Jost B Jonas, Olavi Pärssinen, Juho Wedenoja, Shea Ping Yip, Daniel W H Ho, Chi Pui Pang, Li Jia Chen, Kathryn P Burdon, Jamie E Craig, Barbara E K Klein, Ronald Klein, Toomas Haller, Andres Metspalu, Chiea-Chuen Khor, E-Shyong Tai, Tin Aung, Eranga Vithana, Wan-Ting Tay, Veluchamy A Barathi; Consortium for Refractive Error and Myopia (CREAM); Peng Chen, Ruoying Li, Jiemin Liao, Yingfeng Zheng, Rick T Ong, Angela Döring; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group; David M Evans, Nicholas J Timpson, Annemieke J M H Verkerk, Thomas Meitinger, Olli Raitakari, Felicia Hawthorne, Tim D Spector, Lennart C Karssen, Mario Pirastu, Federico Murgia, Wei Ang; Wellcome Trust Case Control Consortium 2 (WTCCC2); Aniket Mishra, Grant W Montgomery, Craig E Pennell, Phillippa M Cumberland, Ioana Cotlarciuc, Paul Mitchell, Jie Jin Wang, Maria Schache, Sarayut Janmahasatian, Robert P Igo Jr, Jonathan H Lass, Emily Chew, Sudha K Iyengar; Fuchs' Genetics Multi-Center Study Group; Theo G M F Gorgels, Igor Rudan, Caroline Hayward, Alan F Wright, Ozren Polasek, Zoran Vatavuk, James F Wilson, Brian Fleck, Tanja Zeller, Alireza Mirshahi, Christian Müller, André G Uitterlinden, Fernando Rivadeneira, Johannes R Vingerling, Albert Hofman, Ben A Oostra, Najaf Amin, Arthur A B Bergen, Yik-Ying Teo, Jugnoo S Rahi, Veronique Vitart, Cathy Williams, Paul N Baird, Tien-Yin Wong, Konrad Oexle, Norbert Pfeiffer, David A Mackey, Terri L Young, Cornelia M van Duijn, Seang-Mei Saw, Joan E Bailey-Wilson, Dwight Stambolian, Caroline C Klaver, Christopher J Hammond
Collaborators, Affiliations
Meta-Analysis

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Virginie J M Verhoeven et al. Nat Genet. 2013 Mar.

Erratum in

  • Nat Genet. 2013 Jun;45(2):712. Janmahasathian, Sarayut [corrected to Sarayut Janmahasatian]

Abstract

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Manhattan plot of the GWAS meta-analysis for refractive error in the combined analysis (n = 45,758)
The plot shows −log10-transformed P values for all SNPs; the upper horizontal line represents the genome-wide significance threshold of P < 5.0 × 10−8; the lower line indicates P value of 10−5. Previously reported genes are depicted in grey. The A2BP1 gene is also known as RBFOX1.
Figure 2
Figure 2. Genetic risk score for myopia
Distribution of subjects from Rotterdam Study 1-3 (n= 9,307) with myopia (SE ≤ −3 D), emmetropia (SE ≥ −1.5 D & ≤ 1.5 D) and hyperopia (SE ≥ 3 D) as a function of genetic risk score. This score is based on the regression coefficients and allele dosages of the associated SNPs for all 26 loci identified in the meta-analysis. The mean OR of myopia was calculated per risk category, using the middle risk score category (risk score 2.50; 2.75) as a reference.
See this image and copyright information in PMC

References

    1. Wojciechowski R. Nature and nurture: the complex genetics of myopia and refractive error. Clin Genet. 2011;79:301–20. - PMC - PubMed
    1. Mutti DO, et al. Axial growth and changes in lenticular and corneal power during emmetropization in infants. Invest Ophthalmol Vis Sci. 2005;46:3074–80. - PubMed
    1. Smith TS, Frick KD, Holden BA, Fricke TR, Naidoo KS. Potential lost productivity resulting from the global burden of uncorrected refractive error. Bull World Health Organ. 2009;87:431–7. - PMC - PubMed
    1. Solouki AM, et al. A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nat Genet. 2010;42:897–901. - PMC - PubMed
    1. Shi Y, et al. Genetic variants at 13q12.12 are associated with high myopia in the Han Chinese population. Am J Hum Genet. 2011;88:805–13. - PMC - PubMed

Publication types

Associated data

Grants and funding