Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

Claire Simpson, Robert Wojciechowski, Konrad Oexle, Federico Murgia, Laura Portas, Xiaohui Li, J. M.Verhoeven Virginie, 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, Paul Mitchell, Seang Mei Saw & 33 others Maurizio Fossarello, Jie Jin Wang, Ozren Polašek, Harry Campbell, Igor Rudan, Ben A. Oostra, André G. Uitterlinden, Albert Hofman, Fernando Rivadeneira, Najaf Amin, Lennart C. Karssen, Johannes R. Vingerling, Angela Döring, 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, Thomas Meitinger, Joan E. Bailey-Wilson, Dwight Stambolian

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 languageEnglish (US)
Article numbere107110
JournalPloS one
Volume9
Issue number9
DOIs
StatePublished - Sep 18 2014

Fingerprint

Hyperopia
Myopia
meta-analysis
Meta-Analysis
Genes
Genome
loci
genome
Refractive Errors
Refraction
Age of Onset
Eye Axial Length
myopia
Linkage Disequilibrium
linkage disequilibrium
retina
Retina
Alleles
eyes
Phenotype

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Simpson, C., Wojciechowski, R., Oexle, K., Murgia, F., Portas, L., Li, X., ... Stambolian, D. (2014). Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci. PloS one, 9(9), [e107110]. https://doi.org/10.1371/journal.pone.0107110

Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci. / Simpson, Claire; Wojciechowski, Robert; Oexle, Konrad; Murgia, Federico; Portas, Laura; Li, Xiaohui; Virginie, J. M.Verhoeven; Vitart, Veronique; Schache, Maria; Mohsen Hosseini, S.; Hysi, Pirro G.; Raffel, Leslie J.; Cotch, Mary Frances; Chew, Emily; Klein, Barbara E.K.; Klein, Ronald; Wong, Tien Yin; Van Duijn, Cornelia M.; Mitchell, Paul; Saw, Seang Mei; Fossarello, Maurizio; Wang, Jie Jin; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Oostra, Ben A.; Uitterlinden, André G.; Hofman, Albert; Rivadeneira, Fernando; Amin, Najaf; Karssen, Lennart C.; Vingerling, Johannes R.; Döring, Angela; Bettecken, Thomas; Bencic, Goran; Gieger, Christian; Wichmann, H. Erich; Wilson, James F.; Venturini, Cristina; Fleck, Brian; Cumberland, Phillippa M.; Rahi, Jugnoo S.; Hammond, Chris J.; Hayward, Caroline; Wright, Alan F.; Paterson, Andrew D.; Baird, Paul N.; Klaver, Caroline C.W.; Rotter, Jerome I.; Pirastu, Mario; Meitinger, Thomas; Bailey-Wilson, Joan E.; Stambolian, Dwight.

In: PloS one, Vol. 9, No. 9, e107110, 18.09.2014.

Research output: Contribution to journalArticle

Simpson, C, Wojciechowski, R, Oexle, K, Murgia, F, Portas, L, Li, X, Virginie, JMV, Vitart, V, Schache, M, Mohsen Hosseini, S, Hysi, PG, Raffel, LJ, Cotch, MF, Chew, E, Klein, BEK, Klein, R, Wong, TY, Van Duijn, CM, Mitchell, P, Saw, SM, Fossarello, M, Wang, JJ, Polašek, O, Campbell, H, Rudan, I, Oostra, BA, Uitterlinden, AG, Hofman, A, Rivadeneira, F, Amin, N, Karssen, LC, Vingerling, JR, Döring, A, Bettecken, T, Bencic, G, Gieger, C, Wichmann, HE, Wilson, JF, Venturini, C, Fleck, B, Cumberland, PM, Rahi, JS, Hammond, CJ, Hayward, C, Wright, AF, Paterson, AD, Baird, PN, Klaver, CCW, Rotter, JI, Pirastu, M, Meitinger, T, Bailey-Wilson, JE & Stambolian, D 2014, 'Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci', PloS one, vol. 9, no. 9, e107110. https://doi.org/10.1371/journal.pone.0107110
Simpson, Claire ; Wojciechowski, Robert ; Oexle, Konrad ; Murgia, Federico ; Portas, Laura ; Li, Xiaohui ; Virginie, J. M.Verhoeven ; Vitart, Veronique ; Schache, Maria ; Mohsen Hosseini, S. ; Hysi, Pirro G. ; Raffel, Leslie J. ; Cotch, Mary Frances ; Chew, Emily ; Klein, Barbara E.K. ; Klein, Ronald ; Wong, Tien Yin ; Van Duijn, Cornelia M. ; Mitchell, Paul ; Saw, Seang Mei ; Fossarello, Maurizio ; Wang, Jie Jin ; Polašek, Ozren ; Campbell, Harry ; Rudan, Igor ; Oostra, Ben A. ; Uitterlinden, André G. ; Hofman, Albert ; Rivadeneira, Fernando ; Amin, Najaf ; Karssen, Lennart C. ; Vingerling, Johannes R. ; Döring, Angela ; Bettecken, Thomas ; Bencic, Goran ; Gieger, Christian ; Wichmann, H. Erich ; Wilson, James F. ; Venturini, Cristina ; Fleck, Brian ; Cumberland, Phillippa M. ; Rahi, Jugnoo S. ; Hammond, Chris J. ; Hayward, Caroline ; Wright, Alan F. ; Paterson, Andrew D. ; Baird, Paul N. ; Klaver, Caroline C.W. ; Rotter, Jerome I. ; Pirastu, Mario ; Meitinger, Thomas ; Bailey-Wilson, Joan E. ; Stambolian, Dwight. / Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci. In: PloS one. 2014 ; Vol. 9, No. 9.
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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.",
author = "Claire Simpson and Robert Wojciechowski and Konrad Oexle and Federico Murgia and Laura Portas and Xiaohui Li and Virginie, {J. M.Verhoeven} and Veronique Vitart and Maria Schache and {Mohsen Hosseini}, S. and Hysi, {Pirro G.} and Raffel, {Leslie J.} and Cotch, {Mary Frances} and Emily Chew and Klein, {Barbara E.K.} and Ronald Klein and Wong, {Tien Yin} and {Van Duijn}, {Cornelia M.} and Paul Mitchell and Saw, {Seang Mei} and Maurizio Fossarello and Wang, {Jie Jin} and Ozren Polašek and Harry Campbell and Igor Rudan and Oostra, {Ben A.} and Uitterlinden, {Andr{\'e} G.} and Albert Hofman and Fernando Rivadeneira and Najaf Amin and Karssen, {Lennart C.} and Vingerling, {Johannes R.} and Angela D{\"o}ring and Thomas Bettecken and Goran Bencic and Christian Gieger and Wichmann, {H. Erich} and Wilson, {James F.} and Cristina Venturini and Brian Fleck and Cumberland, {Phillippa M.} and Rahi, {Jugnoo S.} and Hammond, {Chris J.} and Caroline Hayward and Wright, {Alan F.} and Paterson, {Andrew D.} and Baird, {Paul N.} and Klaver, {Caroline C.W.} and Rotter, {Jerome I.} and Mario Pirastu and Thomas Meitinger and Bailey-Wilson, {Joan E.} and Dwight Stambolian",
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TY - JOUR

T1 - Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

AU - Simpson, Claire

AU - Wojciechowski, Robert

AU - Oexle, Konrad

AU - Murgia, Federico

AU - Portas, Laura

AU - Li, Xiaohui

AU - Virginie, J. M.Verhoeven

AU - Vitart, Veronique

AU - Schache, Maria

AU - Mohsen Hosseini, S.

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, Paul

AU - Saw, Seang Mei

AU - Fossarello, Maurizio

AU - Wang, Jie Jin

AU - Polašek, Ozren

AU - Campbell, Harry

AU - Rudan, Igor

AU - Oostra, Ben A.

AU - Uitterlinden, André G.

AU - Hofman, Albert

AU - Rivadeneira, Fernando

AU - Amin, Najaf

AU - Karssen, Lennart C.

AU - Vingerling, Johannes R.

AU - Döring, 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

AU - Meitinger, Thomas

AU - Bailey-Wilson, Joan E.

AU - Stambolian, Dwight

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 = 1.25610-8), 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.

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 = 1.25610-8), 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.

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