Quantitative Trait Locus Analysis of SIX1-SIX6 With Retinal Nerve Fiber Layer Thickness in Individuals of European Descent.
Quantitative Trait Locus Analysis of SIX1-SIX6 With Retinal Nerve Fiber Layer Thickness in Individuals of European Descent.
复制标题
DOI：
10.1016/j.ajo.2015.04.001
复制
发表时间：
2015-07
影响因子：
4.2
通讯作者：
Weinreb RN
中科院分区：
文献类型：
--
作者：
Kuo JZ;Zangwill LM;Medeiros FA;Liebmann JM;Girkin CA;Hammel N;Rotter JI;Weinreb RN
进行数量性状位点（QTL）分析，评估欧洲血统个体中SIX1和SIX6之间的位点是否与视网膜神经纤维层（RNFL）厚度相关。观察性、多中心、横断面研究。231名参与者从青光眼诊断创新研究和非洲裔青光眼评估研究中招募。将SIX1-SIX6中的rs10483727与全球和部门RNFL厚度进行关联。采用线性回归分析遗传加性模型进行数量性状分析。采用趋势分析对3个感兴趣的基因型（T/T、C/T、C/C）的全球和行业RNFL平均厚度进行评估。所有模型都根据年龄和性别进行了调整。T等位基因与RNFL厚度的相关方向在全球和不同部门的RNFL区域是一致的。rs10483727中T风险等位基因的每个拷贝与RNFL整体厚度变薄- 0.16 μm相关（β= - 0.16, 95% CI: - 0.28 ~ - 0.03； P=0.01）。类似的模式也出现在部门区域，包括下（P=0.03）、下鼻（P=0.017）、上鼻（P=0.0025）、上（P=0.002）和上颞（P=0.008）。在上象限和下象限观察到最大的差异，支持青光眼RNFL变薄的临床观察。与C/T和C/C基因型相比，T/T基因型受试者的整体RNFL较薄（P=0.044）。T风险等位基因的每个拷贝都具有加性效应，并与较薄的全球和部门RNFL相关。该QTL分析结果进一步支持青光眼病理生理的遗传作用。
To perform a quantitative trait locus (QTL) analysis and evaluate whether a locus between SIX1 and SIX6 is associated with retinal nerve fiber layer (RNFL) thickness in individuals of European descent. Observational, multi-center, cross-sectional study. 231 participants were recruited from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Association of rs10483727 in SIX1-SIX6 with global and sectoral RNFL thickness was performed. Quantitative trait analysis with the additive model of inheritance was analyzed using linear regression. Trend analysis was performed to evaluate the mean global and sectoral RNFL thickness with 3 genotypes of interest (T/T, C/T, C/C). All models were adjusted for age and gender. Direction of association between T allele and RNFL thickness was consistent in the global and different sectoral RNFL regions. Each copy of the T risk allele in rs10483727 was associated with −0.16 μm thinner global RNFL thickness (β=−0.16, 95% CI: −0.28 to −0.03; P=0.01). Similar patterns were found for the sectoral regions, including inferior (P=0.03), inferior-nasal (P=0.017), superior-nasal (P=0.0025), superior (P=0.002) and superior-temporal (P=0.008). The greatest differences were observed in the superior and inferior quadrants, supporting clinical observations for RNFL thinning in glaucoma. Thinner global RNFL was found in subjects with T/T genotypes compared to subjects with C/T and C/C genotypes (P=0.044). Each copy of the T risk allele has an additive effect and was associated with thinner global and sectoral RNFL. Findings from this QTL analysis further support a genetic contribution to glaucoma pathophysiology.