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.