6533b82bfe1ef96bd128cf24
RESEARCH PRODUCT
Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.
Beate St PourcainVilmundur GudnasonTaina RantanenJoan E. Bailey-wilsonAnke TönjesSudha K. IyengarCaroline HaywardBen A. OostraLennart C. KarssenYi LuBarbara E.k. KleinIgor RudanFederico MurgiaWan Ting TayVeronique VitartM. Kamran IkramM. Kamran IkramTien Yin WongJames F. WilsonSeang-mei SawKyoko Ohno-matsuiTin AungChristian WolframLiang Kee GohOzren PolasekOlavi PärssinenCathy WilliamsPaul MitchellThomas MeitingerThomas BetteckenMika KähönenDominiek D. G. DesprietGuðný EiríksdóttirAngela DöringAlireza MirshahiEranga N. VithanaYi-ju LiJie Jin WangJie Jin WangDavid A. MackeyDavid A. MackeyBrian W FleckLaura PortasIsao NakataTõnu EskoGeorge McmahonTanja ZellerTerri L. YoungAlbert V. SmithPhillippa M. CumberlandShomi S. BhattacharyaNorbert PfeifferKarl J. LacknerJohannes R. VingerlingFernando RivadeneiraAndres MetspaluCaroline C W KlaverXin ZhouAlan F. WrightPriya DuggalLeslie J. RaffelAlbert HofmanJugnoo S RahiKenji YamashiroRyo YamadaReedik MägiReedik MägiCornelia M. Van DuijnJeremy A. GuggenheimVirginie J. M. VerhoevenRené HöhnNagahisa YoshimuraXueling SimTerho LehtimäkiHarry CampbellPirro G. HysiKonrad OexleRaphaële CastagnéMary Frances CotchRobert WojciechowskiRobert WojciechowskiE-shyong TaiTim D. SpectorClaire L. SimpsonDwight StambolianYik Ying TeoAndré G. UitterlindenLarry D. AtwoodAbhishek NagPaul N. BairdQiao FanNajaf AminChiea Chuen KhorPaulus T. V. M. De JongXiaohui LiChristopher J HammondSarayut JanmahasatianFumihiko MatsudaAlex W. HewittLeonieke M E Van Koolwijksubject
PopulationLocus (genetics)Genome-wide association studySingle-nucleotide polymorphismBiologyPolymorphism Single Nucleotide03 medical and health sciences0302 clinical medicineMyopiaGeneticsHumansSNPGenetics(clinical)AlleleeducationAllelesGenetics (clinical)Original Investigation030304 developmental biologyGenetic associationGeneticsChromosomes Human Pair 150303 health scienceseducation.field_of_study3. Good healthPhenotype030221 ophthalmology & optometryPopulation studyREdescription
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. Electronic supplementary material The online version of this article (doi:10.1007/s00439-012-1176-0) contains supplementary material, which is available to authorized users.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-01-01 |