Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.
Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.
复制标题
DOI：
10.1007/s00439-012-1176-0
复制
发表时间：
2012-09
期刊：
影响因子：
5.3
通讯作者：
Klaver CC
中科院分区：
文献类型：
--
作者：
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
近视是一种复杂的遗传性疾病，也是工作年龄成年人视力受损的常见原因。全基因组关联研究已经在欧洲血统的高加索人群中确定了染色体15 q14和15 q25上的易感基因座。在这里，我们提出了一个确认和荟萃分析研究，我们评估这两个位点是否也与其他人群的近视。研究人群包括来自屈光不正和近视联盟（CREAM）的31个队列，代表4个不同大陆的55，177名个体; 42，845名白人和12，332名亚洲人。我们对15 q14上的14个单核苷酸多态性（SNP）和15 q25上的5个SNP进行了荟萃分析，采用线性回归分析，以等效球镜作为定量结果，并对年龄和性别进行了调整。我们使用固定效应荟萃分析计算了前SNP等位基因携带者近视与远视的比值比（OR）。在15 q14位点，所有SNP均被显著复制，白人中SNP rs634990的P值最低为3.87 × 10−12，亚洲人中SNP rs 8032019的P值最低为9.65 × 10−4。总体荟萃分析提供了最高SNP rs634990的P值9.20 × 10 - 23。对于风险等位基因rs634990的纯合子携带者，近视与远视的风险为OR 1.88（95% CI 1.64，2.16，P < 0.001），杂合子携带者为OR 1.33（95% CI 1.19，1.49，P < 0.001）。15 q25位点的SNP没有显著复制（最高SNP rs 939661的P值为5.81 × 10−2）。我们的结论是，染色体15 q14的常见变异影响世界各地的高加索人和亚洲人群的近视易感性。本文的在线版本（doi：10.1007/s 00439 -012-1176-0）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1007/s00439-012-1176-0) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.5
作者：
Nakanishi H;Yamada R;Gotoh N;Hayashi H;Yamashiro K;Shimada N;Ohno-Matsui K;Mochizuki M;Saito M;Iida T;Matsuo K;Tajima K;Yoshimura N;Matsuda F
通讯作者：
Matsuda F
影响因子：
4.4
作者：
Lu, Boyu;Jiang, Dan;Zhang, Qingjiong
通讯作者：
Zhang, Qingjiong
影响因子：
16.2
作者：
Deans, MR;Volgyi, B;Paul, DL
通讯作者：
Paul, DL
影响因子：
13.7
作者：
Rose, Kathryn A.;Morgan, Ian G.;Mitchell, Paul
通讯作者：
Mitchell, Paul
影响因子：
30.8
作者：
通讯作者：
--