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


Verhoeven, VJM and Hysi, PG and Saw, S and Vitart, V and Mirshahi, A and Guggenheim, JA and Cotch, MF and Yamashiro, K and Baird, PN and Mackey, DA and Wojciechowski, R and Ikram, MK and Hewitt, A and Duggal, P and Janmahasatian, S and Khor, CC and Fan, Q and Zhou, X and Young, T and Tai, ES and Goh, L and Li, Y and Aung, T and Vithana, EN and Teo, Y and Tay, W and Sim, X and Rudan, I and Hayward, C and Wright, AF and Polasek, O and Campbell, H and Wilson, JFF and Fleck, BW and Nakata, I and Yoshimura, N and Yamada, R and Matsuda, F and Ohno-Matsui, K and Nag, A and McMahon, G and St Pourcain, B and Lu, Y and Rahi, JS and Cumberland, PM and Bhattacharya, SS and Simpson, CL and Atwood, LD and Li, X and Raffel, LJ and Hammond, CJ and Klaver, CCW and Murgia, F and Portas, L and Despriet, DDG and Van Koolwijk, LME and Wolfram, C and Lackner, KJ and Tonjes, A and Magi, R and Lehtimaki, TJ and Kahonen, M and Esko, T and Metspalu, AK and Rantanen, T and Parssinen, O and Klein, BE and Meitinger, TA and Spector, TD and Oostra, BA and Smith, AV and De Jong, PTVM and Hofman, AF and Amin, N and Karssen, LC and Rivadneira, FF and Vingerling, JR and Eiriksdottir, G and Gudnason, VG and Doring, A and Bettecken, T and Uitterlinden, AG and Williams, CJ and Zeller, T and Castagne, R and Oexle, K and Van Duijn, CM and Iyengar, SK and Mitchell, PG and Wang, J and Hohn, R and Pfeiffer, N and Bailey-Wilson, JE and Stambolian, DE and Wong, T, Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium, Human Genetics, 131, (9) pp. 1467-1480. ISSN 1432-1203 (2012) [Refereed Article]

DOI: doi:10.1007/s00439-012-1176-0


yopia 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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Mackey, DA (Professor David Mackey)
UTAS Author:Hewitt, A (Professor Alex Hewitt)
ID Code:95362
Year Published:2012
Web of Science® Times Cited:54
Deposited By:Medicine
Deposited On:2014-09-30
Last Modified:2014-09-30

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