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 & 75 others 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, Gudný 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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1467-1480
Number of pages14
JournalHuman Genetics
Volume131
Issue number9
DOIs
StatePublished - Sep 2012

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Refractive Errors
Myopia
Single Nucleotide Polymorphism
Meta-Analysis
Hyperopia
Odds Ratio
Population
Chromosomes
Alleles
Inborn Genetic Diseases
Genome-Wide Association Study
Vision Disorders
Linear Models
Regression Analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Verhoeven, V. J. M., Hysi, P. G., Saw, S. M., Vitart, V., Mirshahi, A., Guggenheim, J. A., ... 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), 1467-1480. https://doi.org/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. / Verhoeven, Virginie J M; Hysi, Pirro G.; Saw, Seang Mei; Vitart, Veronique; Mirshahi, Alireza; Guggenheim, Jeremy A.; Cotch, Mary Frances; Yamashiro, Kenji; Baird, Paul N.; Mackey, David A.; Wojciechowski, Robert; Kamran Ikram, M.; Hewitt, Alex W.; Duggal, Priya; Janmahasatian, Sarayut; Khor, Chiea Chuen; Fan, Qiao; Zhou, Xin; Young, Terri L.; Tai, E. Shyong; Goh, Liang Kee; Li, Yi Ju; Aung, Tin; Vithana, Eranga; Teo, Yik Ying; Tay, Wanting; Sim, Xueling; Rudan, Igor; Hayward, Caroline; Wright, Alan F.; Polasek, Ozren; Campbell, Harry; Wilson, James F.; Fleck, Brian W.; Nakata, Isao; Yoshimura, Nagahisa; Yamada, Ryo; Matsuda, Fumihiko; Ohno-Matsui, Kyoko; Nag, Abhishek; McMahon, George; St. Pourcain, Beate; Lu, Yi; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Bhattacharya, Shomi; Simpson, Claire L.; Atwood, Larry D.; Li, Xiaohui; Raffel, Leslie J.; Murgia, Federico; Portas, Laura; Despriet, Dominiek D G; Van Koolwijk, Leonieke M E; Wolfram, Christian; Lackner, Karl J.; Tönjes, Anke; Mägi, Reedik; Lehtimäki, Terho; Kähönen, Mika; Esko, Tõnu; Metspalu, Andres; Rantanen, Taina; Pärssinen, Olavi; Klein, Barbara E.; Meitinger, Thomas; Spector, Timothy D.; Oostra, Ben A.; Smith, Albert V.; De Jong, Paulus T V M; Hofman, Albert; Amin, Najaf; Karssen, Lennart C.; Rivadeneira, Fernando; Vingerling, Johannes R.; Eiríksdóttir, Gudný; Gudnason, Vilmundur; Döring, Angela; Bettecken, Thomas; Uitterlinden, André G.; Williams, Cathy; Zeller, Tanja; Castagné, Raphaële; Oexle, Konrad; Van Duijn, Cornelia M.; Iyengar, Sudha K.; Mitchell, Paul; Wang, Jie Jin; Höhn, René; Pfeiffer, Norbert; Bailey-Wilson, Joan E.; Stambolian, Dwight; Wong, Tien Yin; Hammond, Christopher J.; Klaver, Caroline C W.

In: Human Genetics, Vol. 131, No. 9, 09.2012, p. 1467-1480.

Research output: Contribution to journalArticle

Verhoeven, VJM, Hysi, PG, Saw, SM, Vitart, V, Mirshahi, A, Guggenheim, JA, Cotch, MF, Yamashiro, K, Baird, PN, Mackey, DA, Wojciechowski, R, Kamran Ikram, M, 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, 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, TY, 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. 1467-1480. https://doi.org/10.1007/s00439-012-1176-0
Verhoeven, Virginie J M ; Hysi, Pirro G. ; Saw, Seang Mei ; Vitart, Veronique ; Mirshahi, Alireza ; Guggenheim, Jeremy A. ; Cotch, Mary Frances ; Yamashiro, Kenji ; Baird, Paul N. ; Mackey, David A. ; Wojciechowski, Robert ; Kamran Ikram, M. ; Hewitt, Alex W. ; Duggal, Priya ; Janmahasatian, Sarayut ; Khor, Chiea Chuen ; Fan, Qiao ; Zhou, Xin ; Young, Terri L. ; Tai, E. Shyong ; Goh, Liang Kee ; Li, Yi Ju ; Aung, Tin ; Vithana, Eranga ; Teo, Yik Ying ; Tay, Wanting ; Sim, Xueling ; Rudan, Igor ; Hayward, Caroline ; Wright, Alan F. ; Polasek, Ozren ; Campbell, Harry ; Wilson, James F. ; Fleck, Brian W. ; Nakata, Isao ; Yoshimura, Nagahisa ; Yamada, Ryo ; Matsuda, Fumihiko ; Ohno-Matsui, Kyoko ; Nag, Abhishek ; McMahon, George ; St. Pourcain, Beate ; Lu, Yi ; Rahi, Jugnoo S. ; Cumberland, Phillippa M. ; Bhattacharya, Shomi ; Simpson, Claire L. ; Atwood, Larry D. ; Li, Xiaohui ; Raffel, Leslie J. ; Murgia, Federico ; Portas, Laura ; Despriet, Dominiek D G ; Van Koolwijk, Leonieke M E ; Wolfram, Christian ; Lackner, Karl J. ; Tönjes, Anke ; Mägi, Reedik ; Lehtimäki, Terho ; Kähönen, Mika ; Esko, Tõnu ; Metspalu, Andres ; Rantanen, Taina ; Pärssinen, Olavi ; Klein, Barbara E. ; Meitinger, Thomas ; Spector, Timothy D. ; Oostra, Ben A. ; Smith, Albert V. ; De Jong, Paulus T V M ; Hofman, Albert ; Amin, Najaf ; Karssen, Lennart C. ; Rivadeneira, Fernando ; Vingerling, Johannes R. ; Eiríksdóttir, Gudný ; Gudnason, Vilmundur ; Döring, Angela ; Bettecken, Thomas ; Uitterlinden, André G. ; Williams, Cathy ; Zeller, Tanja ; Castagné, Raphaële ; Oexle, Konrad ; Van Duijn, Cornelia M. ; Iyengar, Sudha K. ; Mitchell, Paul ; Wang, Jie Jin ; Höhn, René ; Pfeiffer, Norbert ; Bailey-Wilson, Joan E. ; Stambolian, Dwight ; Wong, Tien Yin ; Hammond, Christopher J. ; Klaver, Caroline C W. / Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium. In: Human Genetics. 2012 ; Vol. 131, No. 9. pp. 1467-1480.
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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.",
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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 - Kamran Ikram, M.

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, Gudný

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 - 2012/9

Y1 - 2012/9

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.

UR - http://www.scopus.com/inward/record.url?scp=84866729828&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866729828&partnerID=8YFLogxK

U2 - 10.1007/s00439-012-1176-0

DO - 10.1007/s00439-012-1176-0

M3 - Article

VL - 131

SP - 1467

EP - 1480

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 9

ER -