Abstract
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 = 1.25610-8), 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 genomewide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value = 9.11610-11) and 8q12 (minimum p value 1.82610-11) 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 language | English (US) |
|---|---|
| Article number | e107110 |
| Journal | PloS one |
| Volume | 9 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 18 2014 |
Bibliographical note
Funding Information:We thank numerous clinicians, clinical staff, patients, and their families for their participation in and dedication to the project; the Ogliastra population and all the individuals who participated in this study. We are very grateful to the municipal administrators for their collaboration to the project and for economic and logistic support. We are extremely appreciative of the support and wisdom provided by Dr. Hemin Chin of the National Eye Institute. The Center for Inherited Disease Research, fully funded through a federal contract (HHSN268200782096C) from National Institutes of Health to The Johns Hopkins University, performed genotyping of the AREDS and KORA cohorts. Clinical data and DNA from the DCCT/EDIC study will be made available through the National Institute of Diabetes and Digestive and Kidney Diseases repository at https://www.niddkrepository.org/niddk/home.do . This manuscript was not prepared under the auspices of and does not represent analyses or conclusions of the NIDDK Central Repositories, or the NIH. Rotterdam Study and ERF thank Ada Hooghart, Corina Brussee, Riet Bernaerts-Biskop, Patricia van Hilten, Pascal Arp, Jeanette Vergeer, Marijn Verkerk and Sander Bervoets.