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

Kleins Lab // Publications // Young Lab // Sep 01 2012

PubMed ID: 22665138

Author(s): Verhoeven VJ, Hysi PG, Saw SM, 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 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 DD, van Koolwijk LM, 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 PT, 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 CC. Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium. Hum Genet. 2012 Sep;131(9):1467-80. doi: 10.1007/s00439-012-1176-0. Epub 2012 Jun 5. PMID 22665138

Journal: Human Genetics, Volume 131, Issue 9, Sep 2012

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.