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Meta-Analysis
. 2012 Sep;131(9):1467-80.
doi: 10.1007/s00439-012-1176-0. Epub 2012 Jun 5.

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

Virginie J M Verhoeven  1 , 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
Affiliations
Meta-Analysis

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

Virginie J M Verhoeven et al. Hum Genet. 2012 Sep.

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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Figures

Fig. 1
Fig. 1
Mean age and distribution of spherical equivalent in all study cohorts
Fig. 2
Fig. 2
Forest plots of odds ratios of myopia (spherical equivalent ≤−3 diopters) versus hyperopia (spherical equivalent ≥+3 diopters) for top SNP rs634990. *For studies without subjects with high or moderate hyperopia, emmetropia was used as a reference group. a Homozygotes carriers of alleles TT versus CC for SNP rs634990. b Heterozygotes carriers of alleles TT versus TC for SNP rs634990
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