A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14

Abbas M Solouki; Virginie J M Verhoeven; Cornelia M van Duijn; Annemieke J M H Verkerk; M Kamran Ikram; Pirro G Hysi; Dominiek D G Despriet; Leonieke M van Koolwijk; Lintje Ho; Wishal D Ramdas; Monika Czudowska; Robert W A M Kuijpers; Najaf Amin; Maksim Struchalin; Yurii S Aulchenko; Gabriel van Rij; Frans C C Riemslag; Terri L Young; David A Mackey; Timothy D Spector; Theo G M F Gorgels; Jacqueline J M Willemse-Assink; Aaron Isaacs; Rogier Kramer; Sigrid M A Swagemakers; Arthur A B Bergen; Andy A L J van Oosterhout; Ben A Oostra; Fernando Rivadeneira; André G Uitterlinden; Albert Hofman; Paulus T V M de Jong; Christopher J Hammond; Johannes R Vingerling; Caroline C W Klaver

doi:10.1038/ng.663

A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14

Abbas M Solouki, Virginie J M Verhoeven, Cornelia M van Duijn, Annemieke J M H Verkerk, M Kamran Ikram, Pirro G Hysi, Dominiek D G Despriet, Leonieke M van Koolwijk, Lintje Ho, Wishal D Ramdas, Monika Czudowska, Robert W A M Kuijpers, Najaf Amin, Maksim Struchalin, Yurii S Aulchenko, Gabriel van Rij, Frans C C Riemslag, Terri L Young, David A Mackey, Timothy D SpectorTheo G M F Gorgels, Jacqueline J M Willemse-Assink, Aaron Isaacs, Rogier Kramer, Sigrid M A Swagemakers, Arthur A B Bergen, Andy A L J van Oosterhout, Ben A Oostra, Fernando Rivadeneira, André G Uitterlinden, Albert Hofman, Paulus T V M de Jong, Christopher J Hammond, Johannes R Vingerling, Caroline C W Klaver^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10⁻¹⁴). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16-1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42-2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.

Original language	English
Pages (from-to)	897-901
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	10
DOIs	https://doi.org/10.1038/ng.663
Publication status	Published - Oct 2010
Externally published	Yes

Keywords

Actins/genetics
Adolescent
Adult
Aged
Case-Control Studies
Chromosomes, Human, Pair 15/genetics
Connexins/genetics
Female
Genetic Predisposition to Disease
Genetic Variation/genetics
Genome, Human
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Myopia/genetics
Young Adult

Access to Document

10.1038/ng.663

Cite this

Solouki, A. M., Verhoeven, V. J. M., van Duijn, C. M., Verkerk, A. J. M. H., Ikram, M. K., Hysi, P. G., Despriet, D. D. G., van Koolwijk, L. M., Ho, L., Ramdas, W. D., Czudowska, M., Kuijpers, R. W. A. M., Amin, N., Struchalin, M., Aulchenko, Y. S., van Rij, G., Riemslag, F. C. C., Young, T. L., Mackey, D. A., ... Klaver, C. C. W. (2010). A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nature Genetics, 42(10), 897-901. https://doi.org/10.1038/ng.663

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title = "A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14",

abstract = "Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10⁻¹⁴). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16-1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42-2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.",

keywords = "Actins/genetics, Adolescent, Adult, Aged, Case-Control Studies, Chromosomes, Human, Pair 15/genetics, Connexins/genetics, Female, Genetic Predisposition to Disease, Genetic Variation/genetics, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Myopia/genetics, Young Adult",

author = "Solouki, {Abbas M} and Verhoeven, {Virginie J M} and {van Duijn}, {Cornelia M} and Verkerk, {Annemieke J M H} and Ikram, {M Kamran} and Hysi, {Pirro G} and Despriet, {Dominiek D G} and {van Koolwijk}, {Leonieke M} and Lintje Ho and Ramdas, {Wishal D} and Monika Czudowska and Kuijpers, {Robert W A M} and Najaf Amin and Maksim Struchalin and Aulchenko, {Yurii S} and {van Rij}, Gabriel and Riemslag, {Frans C C} and Young, {Terri L} and Mackey, {David A} and Spector, {Timothy D} and Gorgels, {Theo G M F} and Willemse-Assink, {Jacqueline J M} and Aaron Isaacs and Rogier Kramer and Swagemakers, {Sigrid M A} and Bergen, {Arthur A B} and {van Oosterhout}, {Andy A L J} and Oostra, {Ben A} and Fernando Rivadeneira and Uitterlinden, {Andr{\'e} G} and Albert Hofman and {de Jong}, {Paulus T V M} and Hammond, {Christopher J} and Vingerling, {Johannes R} and Klaver, {Caroline C W}",

year = "2010",

month = oct,

doi = "10.1038/ng.663",

language = "English",

volume = "42",

pages = "897--901",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

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Solouki, AM, Verhoeven, VJM, van Duijn, CM, Verkerk, AJMH, Ikram, MK, Hysi, PG, Despriet, DDG, van Koolwijk, LM, Ho, L, Ramdas, WD, Czudowska, M, Kuijpers, RWAM, Amin, N, Struchalin, M, Aulchenko, YS, van Rij, G, Riemslag, FCC, Young, TL, Mackey, DA, Spector, TD, Gorgels, TGMF, Willemse-Assink, JJM, Isaacs, A, Kramer, R, Swagemakers, SMA, Bergen, AAB, van Oosterhout, AALJ, Oostra, BA, Rivadeneira, F, Uitterlinden, AG, Hofman, A, de Jong, PTVM, Hammond, CJ, Vingerling, JR & Klaver, CCW 2010, 'A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14', Nature Genetics, vol. 42, no. 10, pp. 897-901. https://doi.org/10.1038/ng.663

TY - JOUR

T1 - A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14

AU - Solouki, Abbas M

AU - Verhoeven, Virginie J M

AU - van Duijn, Cornelia M

AU - Verkerk, Annemieke J M H

AU - Ikram, M Kamran

AU - Hysi, Pirro G

AU - Despriet, Dominiek D G

AU - van Koolwijk, Leonieke M

AU - Ho, Lintje

AU - Ramdas, Wishal D

AU - Czudowska, Monika

AU - Kuijpers, Robert W A M

AU - Amin, Najaf

AU - Struchalin, Maksim

AU - Aulchenko, Yurii S

AU - van Rij, Gabriel

AU - Riemslag, Frans C C

AU - Young, Terri L

AU - Mackey, David A

AU - Spector, Timothy D

AU - Gorgels, Theo G M F

AU - Willemse-Assink, Jacqueline J M

AU - Isaacs, Aaron

AU - Kramer, Rogier

AU - Swagemakers, Sigrid M A

AU - Bergen, Arthur A B

AU - van Oosterhout, Andy A L J

AU - Oostra, Ben A

AU - Rivadeneira, Fernando

AU - Uitterlinden, André G

AU - Hofman, Albert

AU - de Jong, Paulus T V M

AU - Hammond, Christopher J

AU - Vingerling, Johannes R

AU - Klaver, Caroline C W

PY - 2010/10

Y1 - 2010/10

N2 - Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10⁻¹⁴). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16-1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42-2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.

AB - Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10⁻¹⁴). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16-1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42-2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.

KW - Actins/genetics

KW - Adolescent

KW - Adult

KW - Aged

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 15/genetics

KW - Connexins/genetics

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation/genetics

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Myopia/genetics

KW - Young Adult

U2 - 10.1038/ng.663

DO - 10.1038/ng.663

M3 - Article

C2 - 20835239

SN - 1061-4036

VL - 42

SP - 897

EP - 901

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -