Matrix metalloproteinases and educational attainment in refractive error: evidence of gene-environment interactions in the Age-Related Eye Disease Study.
Matrix metalloproteinases and educational attainment in refractive error: evidence of gene-environment interactions in the Age-Related Eye Disease Study.
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DOI：
10.1016/j.ophtha.2012.07.078
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发表时间：
2013-02
期刊：
影响因子：
13.7
通讯作者：
Stambolian D
中科院分区：
文献类型：
--
作者：
Wojciechowski R;Yee SS;Simpson CL;Bailey-Wilson JE;Stambolian D
以前的一项关于旧秩序阿米什家族的研究表明，眼屈光与基质金属蛋白酶（MMP）基因MMP 1和MMP 10近端的标记物以及MMP 2基因内的标记物相关。我们进行了一项候选基因复制研究屈光和单核苷酸多态性（SNP）在这些基因组区域之间的关联。候选基因遗传关联研究。从年龄相关性眼病研究（AREDS）中选出2,000名参与者进行基因分型。经过质量控制过滤，1912人可用于分析。使用HumanOmni 2.5微珠阵列进行微阵列基因分型。在先前的阿米什关联研究中最初分型的SNP被提取用于分析。此外，使用TaqMan测定对单倍型标记SNP进行基因分型。使用线性回归模型和加性遗传风险模型对30个标记物进行平均等效球镜屈光度（MSE）的数量性状关联分析，同时调整年龄、性别、教育和人群亚结构。对二分教育变量进行分层后进行事后分析。逐点（P-emp）和多重检验研究（P-multi）显著性水平通过排列经验计算。MSE用作眼屈光的定量测量。平均年龄和眼屈光度分别为68岁（SD=4.7）和+0.55 D（SD=2.14）。获得rs 1939008的逐点统计学显著性（P-emp=0.0326）。校正多重检验后，没有SNP达到统计学显著性。在分层分析中，多个SNPs在低教育水平组中达到逐点显著性：其中2个在多重检验校正后具有统计学显著性。阿米什人家庭中两个最高等级的SNP（rs 1939008和rs 9928731）在AREDS参与者的低教育阶层中显示逐点P-emp<0.01。我们显示了提示性证据的复制的关联信号眼屈光MMP 1和MMP 10之间的标记。我们还提供了先前报道的标记物和屈光不正教育之间的基因-环境相互作用的证据。MMP 1-MMP 10和MMP 2区域的变异似乎影响了环境条件下近视发展不利的眼屈光的群体变异。
A previous study of Old Order Amish families has shown association of ocular refraction with markers proximal to matrix metalloproteinase (MMP) genes MMP1 and MMP10 and intragenic to MMP2. We conducted a candidate gene replication study of association between refraction and single nucleotide polymorphisms (SNPs) within these genomic regions. Candidate gene genetic association study. 2,000 participants drawn from the Age Related Eye Disease Study (AREDS) were chosen for genotyping. After quality control filtering, 1912 individuals were available for analysis. Microarray genotyping was performed using the HumanOmni 2.5 bead array. SNPs originally typed in the previous Amish association study were extracted for analysis. In addition, haplotype tagging SNPs were genotyped using TaqMan assays. Quantitative trait association analyses of mean spherical equivalent refraction (MSE) were performed on 30 markers using linear regression models and an additive genetic risk model, while adjusting for age, sex, education, and population substructure. Post-hoc analyses were performed after stratifying on a dichotomous education variable. Pointwise (P-emp) and multiple-test study-wise (P-multi) significance levels were calculated empirically through permutation. MSE was used as a quantitative measure of ocular refraction. The mean age and ocular refraction were 68 years (SD=4.7) and +0.55 D (SD=2.14), respectively. Pointwise statistical significance was obtained for rs1939008 (P-emp=0.0326). No SNP attained statistical significance after correcting for multiple testing. In stratified analyses, multiple SNPs reached pointwise significance in the lower-education group: 2 of these were statistically significant after multiple testing correction. The two highest-ranking SNPs in Amish families (rs1939008 and rs9928731) showed pointwise P-emp<0.01 in the lower-education stratum of AREDS participants. We show suggestive evidence of replication of an association signal for ocular refraction to a marker between MMP1 and MMP10. We also provide evidence of a gene-environment interaction between previously-reported markers and education on refractive error. Variants in MMP1- MMP10 and MMP2 regions appear to affect population variation in ocular refraction in environmental conditions less favorable for myopia development.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
4.4
作者：
Leung, Kim Hung;Yiu, Wai Chi;Yip, Shea Ping
通讯作者：
Yip, Shea Ping
影响因子：
4.4
作者：
Siegwart, JT;Norton, TT
通讯作者：
Norton, TT
影响因子：
3.5
作者：
Wojciechowski R
通讯作者：
Wojciechowski R
DOI：
10.1073/pnas.0909344107
发表时间：
2010-02-16
影响因子：
11.1
作者：
Karlic, Rosa;Chung, Ho-Ryun;Vingron, Martin
通讯作者：
Vingron, Martin