Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci

DCCT EDIC Res Grp, Claire L. Simpson, Robert Wojciechowski, Konrad Oexle, Federico Murgia, Laura Portas, Xiaohui Li, Virginie J. M. Verhoeven, Veronique Vitart, Maria Schache, S. Mohsen Hosseini, Pirro G. Hysi, Leslie J. Raffel, Mary Frances Cotch, Emily Chew, Barbara E. K. Klein, Ronald Klein, Tien Yin Wong, Cornelia M. Van Duijn, Rory MitchellSeang Mei Saw, Maurizio Fossarello, Jie Jin Wang, Ozren Polasek, Harry Campbell, Igor Rudan, Ben A. Oostra, Andre G. Uitterlinden, Albert Hofman, Fernando Rivadeneira, Najaf Amin, Lennart C. Karssen, Johannes R. Vingerling, Angela Doering, Thomas Bettecken, Goran Bencic, Christian Gieger, H. -Erich Wichmann, James F. Wilson, Cristina Venturini, Brian Fleck, Phillippa M. Cumberland, Jugnoo S. Rahi, Chris J. Hammond, Caroline Hayward, Alan F. Wright, Andrew D. Paterson, Paul N. Baird, Caroline C. W. Klaver, Jerome I. Rotter, Mario Pirastu

Research output: Contribution to journalArticlepeer-review


Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25×10-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11×10-11) and 8q12 (minimum p value 1.82×10-11) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.

Original languageEnglish
Article number107110
Number of pages19
JournalPLoS ONE
Issue number9
Publication statusPublished - 18 Sep 2014


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