Identification of Novel Genetic Loci for Intraocular Pressure

Abstract

To identify genetic loci that control intraocular pressure (IOP). Methods: We performed a genomewide scan of IOP, using 486 pedigrees ascertained through a populationbased cohort, the Beaver Dam Eye Study. Linkage analysis was performed using the modified Haseman-Elston regression models and variance components linkage analysis. Results: Seven regions of interest were identified on chromosomes 2, 5, 6, 7, 12, 15, and 19. The novel linkage region on chromosome 19p had an empirical multipoint P value of 6.1ϫ10 −5. Two of the regions (2 and 19) were especially interesting since each has been identified as a potential linkage region for blood pressure. Conclusions: The results of this genomewide scan provide evidence that a quantitative trait locus may influence elevated IOP and may colocalize with blood pressure loci. These loci may control systemic pressure reflected in the eye and vascular system. Clinical Relevance: Glaucoma is a leading cause of blindness in the world, and the identification of genes that contribute to this disease is essential. Elevated IOP is a principal risk factor for primary open-angle glaucoma and an intriguing quantitative trait that may strongly influence the development of disease.

Current concepts on primary open-angle glaucoma genetics: a contribution to disease pathophysiology and future treatment

“…137 In the context of establishing a genetic correlation between POAG endophenotypes and POAG, a genome-wide scan of IOP was performed, using 486 pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study. 138 The investigators' purpose was to identify quantitative trait loci controlling IOP and thereby influencing the development of glaucoma. Seven loci of interest were identified (2, 5, 6, 7, 12, 15, and 19) and two of the regions (on chromosomes 2 and 19) co-localized with blood pressure loci.…”

Cardiovascular and Respiratory Considerations With Pharmacotherapy of Glaucoma and Ocular Hypertension

“…167 These loci may control both systemic pressure reflected in the eye and in the vascular system. 166 This observation is the novel beginning of a journey that could lead to the discovery of those genes associated with the control of IOP, which may help in the selection of therapy that can more effectively halt disease progression. 168 …”

Heritability of intraocular pressure: a classical twin study

“…A commingling analysis from the Australian Blue Mountains Eye Study suggested the presence of a major gene contributing to 18% of the variance of IOP 10. Novel genetic loci for IOP have been identified,8 11 – 13 but not yet replicated. The complexity of the phenotypic definition of glaucoma has contributed to the difficulties in identifying genes involved in this disease 14…”