TY - JOUR
T1 - Genome-Wide Meta-Analysis of Myopia and Hyperopia Provides Evidence for Replication of 11 Loci
AU - DCCT EDIC Res Grp
AU - Simpson, Claire L.
AU - Wojciechowski, Robert
AU - Oexle, Konrad
AU - Murgia, Federico
AU - Portas, Laura
AU - Li, Xiaohui
AU - Verhoeven, Virginie J. M.
AU - Vitart, Veronique
AU - Schache, Maria
AU - Hosseini, S. Mohsen
AU - Hysi, Pirro G.
AU - Raffel, Leslie J.
AU - Cotch, Mary Frances
AU - Chew, Emily
AU - Klein, Barbara E. K.
AU - Klein, Ronald
AU - Wong, Tien Yin
AU - Van Duijn, Cornelia M.
AU - Mitchell, Rory
AU - Saw, Seang Mei
AU - Fossarello, Maurizio
AU - Wang, Jie Jin
AU - Polasek, Ozren
AU - Campbell, Harry
AU - Rudan, Igor
AU - Oostra, Ben A.
AU - Uitterlinden, Andre G.
AU - Hofman, Albert
AU - Rivadeneira, Fernando
AU - Amin, Najaf
AU - Karssen, Lennart C.
AU - Vingerling, Johannes R.
AU - Doering, Angela
AU - Bettecken, Thomas
AU - Bencic, Goran
AU - Gieger, Christian
AU - Wichmann, H. -Erich
AU - Wilson, James F.
AU - Venturini, Cristina
AU - Fleck, Brian
AU - Cumberland, Phillippa M.
AU - Rahi, Jugnoo S.
AU - Hammond, Chris J.
AU - Hayward, Caroline
AU - Wright, Alan F.
AU - Paterson, Andrew D.
AU - Baird, Paul N.
AU - Klaver, Caroline C. W.
AU - Rotter, Jerome I.
AU - Pirastu, Mario
PY - 2014/9/18
Y1 - 2014/9/18
N2 - 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.
AB - 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.
KW - RETINAL-PIGMENT EPITHELIUM
KW - AUSTRALIAN SCHOOL-CHILDREN
KW - REFRACTIVE ERROR
KW - LINKAGE-DISEQUILIBRIUM
KW - FAMILIAL AGGREGATION
KW - ASSOCIATION SCANS
KW - OUTDOOR ACTIVITY
KW - COMMON VARIANTS
KW - MULTIPLE
KW - GENE
U2 - 10.1371/journal.pone.0107110
DO - 10.1371/journal.pone.0107110
M3 - Article
C2 - 25233373
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - 107110
ER -