Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Virginie Verhoeven; PG Hysi; SM Saw; V Vitart; A Mirshahi; JA Guggenheim; MF Cotch; K Yamashiro; PN Baird; DA Mackey; R Wojciechowski; Kamran Ikram; AW Hewitt; P Duggal; S Janmahasatian; CC Khor; Q Fan; X Zhou; TL Young; ES Tai; LK Goh; YJ Li; T Aung; E Vithana; YY Teo; W Tay; X Sim; I Rudan; C Hayward; AF Wright; O Polasek; H Campbell; JF Wilson; BW Fleck; I Nakata; N Yoshimura; R Yamada; F Matsuda; K Ohno-Matsui; A Nag; G McMahon; B St Pourcain; Y (Yi) Lu; JS Rahi; PM Cumberland; S Bhattacharya; CL Simpson; LD Atwood; XH Li; LJ Raffel; F Murgia; L Portas; Dominiek Despriet; Leonieke Koolwijk; C Wolfram; KJ Lackner; A Tonjes; R Magi; T Lehtimaki; M Kahonen; T Esko; A Metspalu; T Rantanen; O Parssinen; BE Klein; T Meitinger; TD Spector; Ben Oostra; AV Smith; PTVM (Paulus) de Jong; Bert Hofman; Najaf Amin; Lennart Karssen; Fernando Rivadeneira; Hans Vingerling; G Eiriksdottir; V Gudnason; A Doring; T Bettecken; André Uitterlinden; C Williams; T Zeller; R Castagne; K Oexle; Cornelia Duijn; SK Iyengar; P Mitchell; JJ Wang; R Hohn; N Pfeiffer; JE Bailey-Wilson; D Stambolian; TY Wong; CJ Hammond; Caroline Klaver

doi:10.1007/s00439-012-1176-0

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Virginie Verhoeven, PG Hysi, SM Saw, V Vitart, A Mirshahi, JA Guggenheim, MF Cotch, K Yamashiro, PN Baird, DA Mackey, R Wojciechowski, Kamran Ikram, AW Hewitt, P Duggal, S Janmahasatian, CC Khor, Q Fan, X Zhou, TL Young, ES TaiLK Goh, YJ Li, T Aung, E Vithana, YY Teo, W Tay, X Sim, I Rudan, C Hayward, AF Wright, O Polasek, H Campbell, JF Wilson, BW Fleck, I Nakata, N Yoshimura, R Yamada, F Matsuda, K Ohno-Matsui, A Nag, G McMahon, B St Pourcain, Y (Yi) Lu, JS Rahi, PM Cumberland, S Bhattacharya, CL Simpson, LD Atwood, XH Li, LJ Raffel, F Murgia, L Portas, Dominiek Despriet, Leonieke Koolwijk, C Wolfram, KJ Lackner, A Tonjes, R Magi, T Lehtimaki, M Kahonen, T Esko, A Metspalu, T Rantanen, O Parssinen, BE Klein, T Meitinger, TD Spector, Ben Oostra, AV Smith, PTVM (Paulus) de Jong, Bert Hofman, Najaf Amin, Lennart Karssen, Fernando Rivadeneira, Hans Vingerling, G Eiriksdottir, V Gudnason, A Doring, T Bettecken, André Uitterlinden, C Williams, T Zeller, R Castagne, K Oexle, Cornelia Duijn, SK Iyengar, P Mitchell, JJ Wang, R Hohn, N Pfeiffer, JE Bailey-Wilson, D Stambolian, TY Wong, CJ Hammond, Caroline Klaver

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Abstract

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 x 10(-12) for SNP rs634990 in Caucasians, and 9.65 x 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 x 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 x 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.

Original language	Undefined/Unknown
Pages (from-to)	1467-1480
Number of pages	14
Journal	Human Genetics
Volume	131
Issue number	9
DOIs	https://doi.org/10.1007/s00439-012-1176-0
Publication status	Published - 2012

Research programs

EMC MGC-02-96-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC OR-01-60-01

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Cite this

Verhoeven, V., Hysi, PG., Saw, SM., Vitart, V., Mirshahi, A., Guggenheim, JA., Cotch, MF., Yamashiro, K., Baird, PN., Mackey, DA., Wojciechowski, R., Ikram, K., Hewitt, AW., Duggal, P., Janmahasatian, S., Khor, CC., Fan, Q., Zhou, X., Young, TL., ... Klaver, C. (2012). Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium. Human Genetics, 131(9), 1467-1480. https://doi.org/10.1007/s00439-012-1176-0

@article{a297083132a24c229aa521dd207f7254,

title = "Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium",

abstract = "Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 x 10(-12) for SNP rs634990 in Caucasians, and 9.65 x 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 x 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 x 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.",

author = "Virginie Verhoeven and PG Hysi and SM Saw and V Vitart and A Mirshahi and JA Guggenheim and MF Cotch and K Yamashiro and PN Baird and DA Mackey and R Wojciechowski and Kamran Ikram and AW Hewitt and P Duggal and S Janmahasatian and CC Khor and Q Fan and X Zhou and TL Young and ES Tai and LK Goh and YJ Li and T Aung and E Vithana and YY Teo and W Tay and X Sim and I Rudan and C Hayward and AF Wright and O Polasek and H Campbell and JF Wilson and BW Fleck and I Nakata and N Yoshimura and R Yamada and F Matsuda and K Ohno-Matsui and A Nag and G McMahon and {St Pourcain}, B and Lu, {Y (Yi)} and JS Rahi and PM Cumberland and S Bhattacharya and CL Simpson and LD Atwood and XH Li and LJ Raffel and F Murgia and L Portas and Dominiek Despriet and Leonieke Koolwijk and C Wolfram and KJ Lackner and A Tonjes and R Magi and T Lehtimaki and M Kahonen and T Esko and A Metspalu and T Rantanen and O Parssinen and BE Klein and T Meitinger and TD Spector and Ben Oostra and AV Smith and {de Jong}, {PTVM (Paulus)} and Bert Hofman and Najaf Amin and Lennart Karssen and Fernando Rivadeneira and Hans Vingerling and G Eiriksdottir and V Gudnason and A Doring and T Bettecken and Andr{\'e} Uitterlinden and C Williams and T Zeller and R Castagne and K Oexle and Cornelia Duijn and SK Iyengar and P Mitchell and JJ Wang and R Hohn and N Pfeiffer and JE Bailey-Wilson and D Stambolian and TY Wong and CJ Hammond and Caroline Klaver",

year = "2012",

doi = "10.1007/s00439-012-1176-0",

language = "Undefined/Unknown",

volume = "131",

pages = "1467--1480",

journal = "Human Genetics",

issn = "0340-6717",

publisher = "Springer Science+Business Media",

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Verhoeven, V, Hysi, PG, Saw, SM, Vitart, V, Mirshahi, A, Guggenheim, JA, Cotch, MF, Yamashiro, K, Baird, PN, Mackey, DA, Wojciechowski, R, Ikram, K, Hewitt, AW, Duggal, P, Janmahasatian, S, Khor, CC, Fan, Q, Zhou, X, Young, TL, Tai, ES, Goh, LK, Li, YJ, Aung, T, Vithana, E, Teo, YY, Tay, W, Sim, X, Rudan, I, Hayward, C, Wright, AF, Polasek, O, Campbell, H, Wilson, JF, Fleck, BW, Nakata, I, Yoshimura, N, Yamada, R, Matsuda, F, Ohno-Matsui, K, Nag, A, McMahon, G, St Pourcain, B, Lu, Y, Rahi, JS, Cumberland, PM, Bhattacharya, S, Simpson, CL, Atwood, LD, Li, XH, Raffel, LJ, Murgia, F, Portas, L, Despriet, D, Koolwijk, L, Wolfram, C, Lackner, KJ, Tonjes, A, Magi, R, Lehtimaki, T, Kahonen, M, Esko, T, Metspalu, A, Rantanen, T, Parssinen, O, Klein, BE, Meitinger, T, Spector, TD, Oostra, B, Smith, AV, de Jong, PTVM, Hofman, B , Amin, N, Karssen, L, Rivadeneira, F , Vingerling, H, Eiriksdottir, G, Gudnason, V, Doring, A, Bettecken, T, Uitterlinden, A, Williams, C, Zeller, T, Castagne, R, Oexle, K, Duijn, C, Iyengar, SK, Mitchell, P, Wang, JJ, Hohn, R, Pfeiffer, N, Bailey-Wilson, JE, Stambolian, D, Wong, TY, Hammond, CJ & Klaver, C 2012, 'Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium', Human Genetics, vol. 131, no. 9, pp. 1467-1480. https://doi.org/10.1007/s00439-012-1176-0

TY - JOUR

T1 - Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

AU - Verhoeven, Virginie

AU - Hysi, PG

AU - Saw, SM

AU - Vitart, V

AU - Mirshahi, A

AU - Guggenheim, JA

AU - Cotch, MF

AU - Yamashiro, K

AU - Baird, PN

AU - Mackey, DA

AU - Wojciechowski, R

AU - Ikram, Kamran

AU - Hewitt, AW

AU - Duggal, P

AU - Janmahasatian, S

AU - Khor, CC

AU - Fan, Q

AU - Zhou, X

AU - Young, TL

AU - Tai, ES

AU - Goh, LK

AU - Li, YJ

AU - Aung, T

AU - Vithana, E

AU - Teo, YY

AU - Tay, W

AU - Sim, X

AU - Rudan, I

AU - Hayward, C

AU - Wright, AF

AU - Polasek, O

AU - Campbell, H

AU - Wilson, JF

AU - Fleck, BW

AU - Nakata, I

AU - Yoshimura, N

AU - Yamada, R

AU - Matsuda, F

AU - Ohno-Matsui, K

AU - Nag, A

AU - McMahon, G

AU - St Pourcain, B

AU - Lu, Y (Yi)

AU - Rahi, JS

AU - Cumberland, PM

AU - Bhattacharya, S

AU - Simpson, CL

AU - Atwood, LD

AU - Li, XH

AU - Raffel, LJ

AU - Murgia, F

AU - Portas, L

AU - Despriet, Dominiek

AU - Koolwijk, Leonieke

AU - Wolfram, C

AU - Lackner, KJ

AU - Tonjes, A

AU - Magi, R

AU - Lehtimaki, T

AU - Kahonen, M

AU - Esko, T

AU - Metspalu, A

AU - Rantanen, T

AU - Parssinen, O

AU - Klein, BE

AU - Meitinger, T

AU - Spector, TD

AU - Oostra, Ben

AU - Smith, AV

AU - de Jong, PTVM (Paulus)

AU - Hofman, Bert

AU - Amin, Najaf

AU - Karssen, Lennart

AU - Rivadeneira, Fernando

AU - Vingerling, Hans

AU - Eiriksdottir, G

AU - Gudnason, V

AU - Doring, A

AU - Bettecken, T

AU - Uitterlinden, André

AU - Williams, C

AU - Zeller, T

AU - Castagne, R

AU - Oexle, K

AU - Duijn, Cornelia

AU - Iyengar, SK

AU - Mitchell, P

AU - Wang, JJ

AU - Hohn, R

AU - Pfeiffer, N

AU - Bailey-Wilson, JE

AU - Stambolian, D

AU - Wong, TY

AU - Hammond, CJ

AU - Klaver, Caroline

PY - 2012

Y1 - 2012

N2 - Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 x 10(-12) for SNP rs634990 in Caucasians, and 9.65 x 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 x 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 x 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.

AB - Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 x 10(-12) for SNP rs634990 in Caucasians, and 9.65 x 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 x 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 x 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.

U2 - 10.1007/s00439-012-1176-0

DO - 10.1007/s00439-012-1176-0

M3 - Article

C2 - 22665138

SN - 0340-6717

VL - 131

SP - 1467

EP - 1480

JO - Human Genetics

JF - Human Genetics

IS - 9

ER -