PURPOSE. To investigate a potential genetic contribution to intraocular pressure (IOP), we performed a complex segregation analysis on 2337 individuals in 620 extended pedigrees ascertained through a population- based...PURPOSE. To investigate a potential genetic contribution to intraocular pressure (IOP), we performed a complex segregation analysis on 2337 individuals in 620 extended pedigrees ascertained through a population- based cohort, the Beaver Dam Eye Study (BDES). IOP is a principal risk factor for primary open- angle glaucoma (POAG) a leading cause of blindness worldwide. METHODS. Segregation analysis is an analytical method that provides statistical evidence supporting the involvement of a major gene or polygenes in a particular phenotype. Detailed medical histories and eye examinations were performed on all participants. From the two eyes, the higher IOP measurement was used as a continuous trait after adjustment for covariates. Agenome- wide scan(GWS) using affected sib pair linkage analysis was performed on 218 sibling pairs. RESULTS. In this segregation analysis the model that allowed for an unmeasured major environmental effect plus a polygenic/ multifactorial effect provided the best fit and was the most parsimonious model. The lack of an adequate fit for the Mendelian single- gene models is consistent with a multifactorial model of inheritance that may include multiple genes and environmental factors that contribute to IOP. The results of the GWS yielded two novel loci as potential linkage regions for IOP on chromosomes 6 (P=0.008) and 13 (P=0.0007). Neither of these regions has previously been identified in GWS of POAG. CONCLUSIONS. The segregation and familial correlation analyses of IOP suggest a polygenetic component with environmental influences. The pilot linkage study further con- firms the heterogeneity of IOP with the identification of two novel genetic loci.展开更多
PURPOSE. Refractive errors, myopia, and hyperopia are common conditions requiring corrective lenses. The familial clustering of myopia has been well established. Several chromosomal regions have been linked to high my...PURPOSE. Refractive errors, myopia, and hyperopia are common conditions requiring corrective lenses. The familial clustering of myopia has been well established. Several chromosomal regions have been linked to high myopia (12q, 17q, and 18q), to quantitative refraction among twins (3q,4q, 8p, and 11p), and to families with moderate myopia (22q). This study examined the familial aggregation and pattern of inheritance of ocular refraction in an adult population, by using data from the Beaver Dam Eye Study. METHODS. Familial correlations were examined and segregation analysis was performed on the average refractive error measurements in the right and left eyes after adjustment for age, sex, and education. Analyses were based on 2138 individuals in 620 extended pedigrees with complete data on age, sex, education, and spherical equivalent. RESULTS. Substantial positive correlation was found between siblings (0.33), parents and offspring (0.17), and cousins (0.10) and lower correlation among avuncular pairs (0.08) after adjustment for age, sex, and years of education. The results of this segregation analysis do not support the involvement of a single major locus throughout the entire range of refractive error. However,models allowing for familial correlation, attributable in part to polygenic effects, provided a better fit to the observed data than models without a polygenic component, suggesting that several genes of modest effect may influence refractive error, possibly in conjunction with environmental factors. CONCLUSIONS. These results support the involvement of genetic factors in the etiology of refractive error and are consistent with reports of linkage to multiple regions of the genome.展开更多
文摘PURPOSE. To investigate a potential genetic contribution to intraocular pressure (IOP), we performed a complex segregation analysis on 2337 individuals in 620 extended pedigrees ascertained through a population- based cohort, the Beaver Dam Eye Study (BDES). IOP is a principal risk factor for primary open- angle glaucoma (POAG) a leading cause of blindness worldwide. METHODS. Segregation analysis is an analytical method that provides statistical evidence supporting the involvement of a major gene or polygenes in a particular phenotype. Detailed medical histories and eye examinations were performed on all participants. From the two eyes, the higher IOP measurement was used as a continuous trait after adjustment for covariates. Agenome- wide scan(GWS) using affected sib pair linkage analysis was performed on 218 sibling pairs. RESULTS. In this segregation analysis the model that allowed for an unmeasured major environmental effect plus a polygenic/ multifactorial effect provided the best fit and was the most parsimonious model. The lack of an adequate fit for the Mendelian single- gene models is consistent with a multifactorial model of inheritance that may include multiple genes and environmental factors that contribute to IOP. The results of the GWS yielded two novel loci as potential linkage regions for IOP on chromosomes 6 (P=0.008) and 13 (P=0.0007). Neither of these regions has previously been identified in GWS of POAG. CONCLUSIONS. The segregation and familial correlation analyses of IOP suggest a polygenetic component with environmental influences. The pilot linkage study further con- firms the heterogeneity of IOP with the identification of two novel genetic loci.
文摘PURPOSE. Refractive errors, myopia, and hyperopia are common conditions requiring corrective lenses. The familial clustering of myopia has been well established. Several chromosomal regions have been linked to high myopia (12q, 17q, and 18q), to quantitative refraction among twins (3q,4q, 8p, and 11p), and to families with moderate myopia (22q). This study examined the familial aggregation and pattern of inheritance of ocular refraction in an adult population, by using data from the Beaver Dam Eye Study. METHODS. Familial correlations were examined and segregation analysis was performed on the average refractive error measurements in the right and left eyes after adjustment for age, sex, and education. Analyses were based on 2138 individuals in 620 extended pedigrees with complete data on age, sex, education, and spherical equivalent. RESULTS. Substantial positive correlation was found between siblings (0.33), parents and offspring (0.17), and cousins (0.10) and lower correlation among avuncular pairs (0.08) after adjustment for age, sex, and years of education. The results of this segregation analysis do not support the involvement of a single major locus throughout the entire range of refractive error. However,models allowing for familial correlation, attributable in part to polygenic effects, provided a better fit to the observed data than models without a polygenic component, suggesting that several genes of modest effect may influence refractive error, possibly in conjunction with environmental factors. CONCLUSIONS. These results support the involvement of genetic factors in the etiology of refractive error and are consistent with reports of linkage to multiple regions of the genome.
