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

Virginie J M Verhoeven; Pirro G Hysi; Seang-Mei Saw; Veronique Vitart; Alireza Mirshahi; Jeremy A Guggenheim; Mary Frances Cotch; Kenji Yamashiro; Paul N Baird; David A Mackey; Robert Wojciechowski; M Kamran Ikram; Alex W Hewitt; Priya Duggal; Sarayut Janmahasatian; Chiea-Chuen Khor; Qiao Fan; Xin Zhou; Terri L Young; E-Shyong Tai; Liang-Kee Goh; Yi-Ju Li; Tin Aung; Eranga Vithana; Yik-Ying Teo; Wanting Tay; Xueling Sim; Igor Rudan; Caroline Hayward; Alan F Wright; Ozren Polasek; Harry Campbell; James F Wilson; Brian W Fleck; Isao Nakata; Nagahisa Yoshimura; Ryo Yamada; Fumihiko Matsuda; Kyoko Ohno-Matsui; Abhishek Nag; George McMahon; Beate St Pourcain; Yi Lu; Jugnoo S Rahi; Phillippa M Cumberland; Shomi Bhattacharya; Claire L Simpson; Larry D Atwood; Xiaohui Li; Leslie J Raffel; Federico Murgia; Laura Portas; Dominiek D G Despriet; Leonieke M E van Koolwijk; Christian Wolfram; Karl J Lackner; Anke Tönjes; Reedik Mägi; Terho Lehtimäki; Mika Kähönen; Tõnu Esko; Andres Metspalu; Taina Rantanen; Olavi Pärssinen; Barbara E Klein; Thomas Meitinger; Timothy D Spector; Ben A Oostra; Albert V Smith; Paulus T V M de Jong; Albert Hofman; Najaf Amin; Lennart C Karssen; Fernando Rivadeneira; Johannes R Vingerling; Guðný Eiríksdóttir; Vilmundur Gudnason; Angela Döring; Thomas Bettecken; André G Uitterlinden; Cathy Williams; Tanja Zeller; Raphaële Castagné; Konrad Oexle; Cornelia M van Duijn; Sudha K Iyengar; Paul Mitchell; Jie Jin Wang; René Höhn; Norbert Pfeiffer; Joan E Bailey-Wilson; Dwight Stambolian; Tien-Yin Wong; Christopher J Hammond; Caroline C W 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 J M Verhoeven, Pirro G Hysi, Seang-Mei Saw, Veronique Vitart, Alireza Mirshahi, Jeremy A Guggenheim, Mary Frances Cotch, Kenji Yamashiro, Paul N Baird, David A Mackey, Robert Wojciechowski, M Kamran Ikram, Alex W Hewitt, Priya Duggal, Sarayut Janmahasatian, Chiea-Chuen Khor, Qiao Fan, Xin Zhou, Terri L Young, E-Shyong TaiLiang-Kee Goh, Yi-Ju Li, Tin Aung, Eranga Vithana, Yik-Ying Teo, Wanting Tay, Xueling Sim, Igor Rudan, Caroline Hayward, Alan F Wright, Ozren Polasek, Harry Campbell, James F Wilson, Brian W Fleck, Isao Nakata, Nagahisa Yoshimura, Ryo Yamada, Fumihiko Matsuda, Kyoko Ohno-Matsui, Abhishek Nag, George McMahon, Beate St Pourcain, Yi Lu, Jugnoo S Rahi, Phillippa M Cumberland, Shomi Bhattacharya, Claire L Simpson, Larry D Atwood, Xiaohui Li, Leslie J Raffel, Federico Murgia, Laura Portas, Dominiek D G Despriet, Leonieke M E van Koolwijk, Christian Wolfram, Karl J Lackner, Anke Tönjes, Reedik Mägi, Terho Lehtimäki, Mika Kähönen, Tõnu Esko, Andres Metspalu, Taina Rantanen, Olavi Pärssinen, Barbara E Klein, Thomas Meitinger, Timothy D Spector, Ben A Oostra, Albert V Smith, Paulus T V M de Jong, Albert Hofman, Najaf Amin, Lennart C Karssen, Fernando Rivadeneira, Johannes R Vingerling, Guðný Eiríksdóttir, Vilmundur Gudnason, Angela Döring, Thomas Bettecken, André G Uitterlinden, Cathy Williams, Tanja Zeller, Raphaële Castagné, Konrad Oexle, Cornelia M van Duijn, Sudha K Iyengar, Paul Mitchell, Jie Jin Wang, René Höhn, Norbert Pfeiffer, Joan E Bailey-Wilson, Dwight Stambolian, Tien-Yin Wong, Christopher J Hammond, Caroline C W 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 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 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 × 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	English
Pages (from-to)	1467-80
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

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Verhoeven, V. J. M., Hysi, P. G., Saw, S-M., Vitart, V., Mirshahi, A., Guggenheim, J. A., Cotch, M. F., Yamashiro, K., Baird, P. N., Mackey, D. A., Wojciechowski, R., Ikram, M. K., Hewitt, A. W., Duggal, P., Janmahasatian, S., Khor, C-C., Fan, Q., Zhou, X., Young, T. L., ... Klaver, C. C. W. (2012). Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium. Human Genetics, 131(9), 1467-80. https://doi.org/10.1007/s00439-012-1176-0

@article{5d12340ffeff4e1fa6fe004da8c84c61,

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 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 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 × 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 = "Verhoeven, {Virginie J M} and Hysi, {Pirro G} and Seang-Mei Saw and Veronique Vitart and Alireza Mirshahi and Guggenheim, {Jeremy A} and Cotch, {Mary Frances} and Kenji Yamashiro and Baird, {Paul N} and Mackey, {David A} and Robert Wojciechowski and Ikram, {M Kamran} and Hewitt, {Alex W} and Priya Duggal and Sarayut Janmahasatian and Chiea-Chuen Khor and Qiao Fan and Xin Zhou and Young, {Terri L} and E-Shyong Tai and Liang-Kee Goh and Yi-Ju Li and Tin Aung and Eranga Vithana and Yik-Ying Teo and Wanting Tay and Xueling Sim and Igor Rudan and Caroline Hayward and Wright, {Alan F} and Ozren Polasek and Harry Campbell and Wilson, {James F} and Fleck, {Brian W} and Isao Nakata and Nagahisa Yoshimura and Ryo Yamada and Fumihiko Matsuda and Kyoko Ohno-Matsui and Abhishek Nag and George McMahon and {St Pourcain}, Beate and Yi Lu and Rahi, {Jugnoo S} and Cumberland, {Phillippa M} and Shomi Bhattacharya and Simpson, {Claire L} and Atwood, {Larry D} and Xiaohui Li and Raffel, {Leslie J} and Federico Murgia and Laura Portas and Despriet, {Dominiek D G} and {van Koolwijk}, {Leonieke M E} and Christian Wolfram and Lackner, {Karl J} and Anke T{\"o}njes and Reedik M{\"a}gi and Terho Lehtim{\"a}ki and Mika K{\"a}h{\"o}nen and T{\~o}nu Esko and Andres Metspalu and Taina Rantanen and Olavi P{\"a}rssinen and Klein, {Barbara E} and Thomas Meitinger and Spector, {Timothy D} and Oostra, {Ben A} and Smith, {Albert V} and {de Jong}, {Paulus T V M} and Albert Hofman and Najaf Amin and Karssen, {Lennart C} and Fernando Rivadeneira and Vingerling, {Johannes R} and Gu{\dh}n{\'y} Eir{\'i}ksd{\'o}ttir and Vilmundur Gudnason and Angela D{\"o}ring and Thomas Bettecken and Uitterlinden, {Andr{\'e} G} and Cathy Williams and Tanja Zeller and Rapha{\"e}le Castagn{\'e} and Konrad Oexle and {van Duijn}, {Cornelia M} and Iyengar, {Sudha K} and Paul Mitchell and Wang, {Jie Jin} and Ren{\'e} H{\"o}hn and Norbert Pfeiffer and Bailey-Wilson, {Joan E} and Dwight Stambolian and Tien-Yin Wong and Hammond, {Christopher J} and Klaver, {Caroline C W}",

year = "2012",

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

language = "English",

volume = "131",

pages = "1467--80",

journal = "Human Genetics",

issn = "0340-6717",

publisher = "Springer Berlin Heidelberg",

number = "9",

}

Verhoeven, VJM, Hysi, PG, Saw, S-M, Vitart, V, Mirshahi, A, Guggenheim, JA, Cotch, MF, Yamashiro, K, Baird, PN, Mackey, DA, Wojciechowski, R, Ikram, MK, Hewitt, AW, Duggal, P, Janmahasatian, S, Khor, C-C, Fan, Q, Zhou, X, Young, TL, Tai, E-S, Goh, L-K, Li, Y-J, Aung, T, Vithana, E, Teo, Y-Y, 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, X, Raffel, LJ, Murgia, F, Portas, L, Despriet, DDG, van Koolwijk, LME, Wolfram, C, Lackner, KJ, Tönjes, A, Mägi, R, Lehtimäki, T, Kähönen, M, Esko, T, Metspalu, A, Rantanen, T, Pärssinen, O, Klein, BE, Meitinger, T, Spector, TD, Oostra, BA, Smith, AV, de Jong, PTVM, Hofman, A, Amin, N, Karssen, LC, Rivadeneira, F, Vingerling, JR, Eiríksdóttir, G, Gudnason, V, Döring, A, Bettecken, T, Uitterlinden, AG, Williams, C, Zeller, T, Castagné, R, Oexle, K, van Duijn, CM, Iyengar, SK, Mitchell, P, Wang, JJ, Höhn, R, Pfeiffer, N, Bailey-Wilson, JE, Stambolian, D, Wong, T-Y, Hammond, CJ & Klaver, CCW 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. 1467-80. 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 J M

AU - Hysi, Pirro G

AU - Saw, Seang-Mei

AU - Vitart, Veronique

AU - Mirshahi, Alireza

AU - Guggenheim, Jeremy A

AU - Cotch, Mary Frances

AU - Yamashiro, Kenji

AU - Baird, Paul N

AU - Mackey, David A

AU - Wojciechowski, Robert

AU - Ikram, M Kamran

AU - Hewitt, Alex W

AU - Duggal, Priya

AU - Janmahasatian, Sarayut

AU - Khor, Chiea-Chuen

AU - Fan, Qiao

AU - Zhou, Xin

AU - Young, Terri L

AU - Tai, E-Shyong

AU - Goh, Liang-Kee

AU - Li, Yi-Ju

AU - Aung, Tin

AU - Vithana, Eranga

AU - Teo, Yik-Ying

AU - Tay, Wanting

AU - Sim, Xueling

AU - Rudan, Igor

AU - Hayward, Caroline

AU - Wright, Alan F

AU - Polasek, Ozren

AU - Campbell, Harry

AU - Wilson, James F

AU - Fleck, Brian W

AU - Nakata, Isao

AU - Yoshimura, Nagahisa

AU - Yamada, Ryo

AU - Matsuda, Fumihiko

AU - Ohno-Matsui, Kyoko

AU - Nag, Abhishek

AU - McMahon, George

AU - St Pourcain, Beate

AU - Lu, Yi

AU - Rahi, Jugnoo S

AU - Cumberland, Phillippa M

AU - Bhattacharya, Shomi

AU - Simpson, Claire L

AU - Atwood, Larry D

AU - Li, Xiaohui

AU - Raffel, Leslie J

AU - Murgia, Federico

AU - Portas, Laura

AU - Despriet, Dominiek D G

AU - van Koolwijk, Leonieke M E

AU - Wolfram, Christian

AU - Lackner, Karl J

AU - Tönjes, Anke

AU - Mägi, Reedik

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Esko, Tõnu

AU - Metspalu, Andres

AU - Rantanen, Taina

AU - Pärssinen, Olavi

AU - Klein, Barbara E

AU - Meitinger, Thomas

AU - Spector, Timothy D

AU - Oostra, Ben A

AU - Smith, Albert V

AU - de Jong, Paulus T V M

AU - Hofman, Albert

AU - Amin, Najaf

AU - Karssen, Lennart C

AU - Rivadeneira, Fernando

AU - Vingerling, Johannes R

AU - Eiríksdóttir, Guðný

AU - Gudnason, Vilmundur

AU - Döring, Angela

AU - Bettecken, Thomas

AU - Uitterlinden, André G

AU - Williams, Cathy

AU - Zeller, Tanja

AU - Castagné, Raphaële

AU - Oexle, Konrad

AU - van Duijn, Cornelia M

AU - Iyengar, Sudha K

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Höhn, René

AU - Pfeiffer, Norbert

AU - Bailey-Wilson, Joan E

AU - Stambolian, Dwight

AU - Wong, Tien-Yin

AU - Hammond, Christopher J

AU - Klaver, Caroline C W

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 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 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 × 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 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 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 × 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 (Academic Journal)

C2 - 22665138

VL - 131

SP - 1467

EP - 1480

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 9

ER -

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

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