Genetic Analysis of Refractive Error and Related Biometric Traits

描述（由申请人提供）：本提案的目的是进一步检查屈光的遗传基础和屈光的基本生物测定决定因素，特别是眼轴长度、透镜厚度、角膜曲率和前房深度。本研究将使用作为比弗坝眼科研究的一部分收集的数据，并建立在Alison Klein博士、比弗坝眼科研究的研究者（Barbara和罗纳德Klein博士）和NHGRI的研究者（Bailey-Wilson博士）之间正在进行的合作基础上，以了解年龄相关性眼病的遗传基础。本研究的主要目的是使用微卫星和SNP标记组合对屈光度、眼轴长度、透镜厚度、角膜曲率和前房深度进行全基因组数量性状连锁分析。这项工作扩展了我们以前的全基因组连锁分析折射作为一个数量性状的比弗坝眼睛研究，只使用微卫星标记。对于完整的比弗坝眼科研究家族资源，目前可获得来自CIDR的全基因组微卫星标记基因型，并且这些数据的全基因组SNP基因分型目前正在CIDR进行。首先，在调整包括年龄、性别、教育、核硬化在内的其他因素之前和之后，将对个体性状以及性状联合进行广泛的家族相关性分析和混合分析。也可以进行分离分析。其次，将使用屈光、眼轴长度、透镜厚度、角膜曲率和前房深度的组合图（微卫星和SNP）进行定量连锁分析。我们还将对这些特征的联合效应进行分析。考虑到这些生物特征中的每一个在整个屈光范围内的影响，并且所有这些特征都是高度遗传的;分析这些特征的遗传基础将有助于我们了解屈光不正发展的复杂生物学基础。此外，检查屈光不正的遗传学和影响屈光的潜在生物测定决定因素的遗传基础不仅可以提高我们对屈光生物学的理解，而且还可以允许开发干预措施来改变屈光不正的发展，减少矫正的需要。 透镜和矫正手术。

DESCRIPTION (provided by applicant): This goal of this proposal is to further examine the genetic basis of refraction and the underlying biometric determinants of refraction specifically axial length, lens thickness, corneal curvature and anterior chamber depth. This study will use data collected as part of the Beaver Dam Eye Study and builds on an ongoing collaboration to understand the genetic basis of age-related eye disease between Dr. Alison Klein, the Investigators of the Beaver Dam Eye Study (Drs. Barbara and Ronald Klein) and investigators at NHGRI (Dr. Bailey-Wilson). The primary objective of this study is to perform genome-wide quantitative trait linkage analysis of refraction, axial length, lens thickness, corneal curvature and anterior chamber depth using a combined microsatillite and SNP marker set. This work expands on our previous genome-wide linkage analysis of refraction as a quantitative trait in the Beaver Dam Eye Study using only microsatillite markers. For the complete Beaver Dam Eye Study family resource, genome-wide microsatillite marker genotypes from CIDR are currently available and genome-wide SNP genotyping of these data are currently underway at CIDR. First, extensive familial correlation analysis and commingling analysis for individual traits as well as for traits jointly, both before and after adjustment for additional factors including age, sex, education, nuclear sclerosis will be conducted. Segregation analysis may also be performed. Secondly, quantitative linkage analysis using a combined map (microsatillte and SNP) for refraction, axial length, lens thickness, corneal curvature and anterior chamber depth will be performed. We will also perform analysis of the joint effects of these traits. Given the influence of each of these biometric traits across the entire spectrum of refraction and that all of these traits are highly heritable; analysis of the genetic basis of these traits will help us understand the complex biology underlying the development of refractive errors. Additionally, examination of the genetics of refractive error and genetic basis of the underlying biometric determinants that influence refraction may not only improve our understanding of the biology of refraction but may also permit the development of interventions to alter the development of refractive errors reducing the need for corrective lens and corrective surgery.