New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk.

Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations.

Common genetic determinants of intraocular pressure and primary open-angle glaucoma.

Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands.

Gene finding in primary open-angle glaucoma.

There is extensive evidence that there is a genetic component to developing primary open-angle glaucoma (POAG). Unraveling this genetic component might clarify the pathophysiology of the disease and greatly assist in treatment and prevention of visual loss of many thousands of individuals. Linkage and association studies have helped identify loci and genes involved.

A genetic epidemiologic study of candidate genes involved in the optic nerve head morphology.

Purpose: The size of the optic nerve head, referred to as disc area (DA), and the vertical cup-disc ratio (VCDR), are clinically relevant parameters for glaucomatous optic neuropathy. Although these measures have a high heritability, little is known about the underlying genes. Previously, the genes SALL1 and SIX1 were found to be genome-wide significantly associated with DA and VCDR.

Clinical implications of old and new genes for open-angle glaucoma.

Objective: Genome-wide association studies have revealed new insights into the genetic determinants of open-angle glaucoma (OAG). This study was performed to determine to what extent variants within established genes (MYOC, OPTN, and WDR36) and newly identified common genetic variants (ATOH7, CDKN2B, and SIX1) contribute to the risk of OAG.

Design: Population-based setting, family-based setting, and a case-control study.

Common genetic variants associated with open-angle glaucoma.

Open-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma.

Genetic architecture of open angle glaucoma and related determinants.

Background: Although the vertical cup-disc ratio (VCDR) and intraocular pressure (IOP) are important determinants of open angle glaucoma (OAG), it is unclear to what extent the genetic origin of these traits overlap with those of OAG. We evaluated whether the same genes that determine VCDR and IOP also predict OAG.

Methods: Genetic risk scores were constructed from single nucleotide polymorphisms (SNPs) using genome wide association data of 9326 participants from the Rotterdam Study cohorts (mean ± SD age: 64.

A genome-wide association study of optic disc parameters.

The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined.

Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma.

Glaucoma, a main cause of blindness in the developed world, is characterized by progressive degeneration of retinal ganglion cells (RGCs), resulting in irreversible loss of vision. Although members of the neurotrophin gene family in various species are known to support the survival of numerous neuronal populations, including RGCs, it is less clear whether they are also required for survival and maintenance of adult neurons in humans. Here, we report seven different heterozygous mutations in the Neurotrophin-4 (NTF4) gene accounting for about 1.

Major genetic effects in glaucoma: commingling analysis of optic disc parameters in an older Australian population.

Purpose: To test the hypothesis that there is a major genetic determinant of vertical disc diameter (VDD) and vertical cup-to-disc ratio (VCDR) in a large, population-based sample.

Methods: Data were collected from 3654 individuals, 49 years of age or older, participating in the Blue Mountains Eye Study. VDD and VCDR were determined from stereo optic disc photographs.

Association of cognitive functioning with retinal nerve fiber layer thickness.

Purpose: The brain areas that are responsible for cognitive functioning have the same embryonic origin as the retina. The association between cognitive functioning and retinal nerve fiber layer (RNFL) thickness was assessed in a large, population-based sample.

Methods: Neuropsychological and ophthalmic examinations were performed in 1485 healthy individuals (mean age, 46 years; range, 18-85) from the Erasmus Rucphen Family (ERF) study, a study in a genetic isolate from the Netherlands.

Genetic contributions to glaucoma: heritability of intraocular pressure, retinal nerve fiber layer thickness, and optic disc morphology.

Purpose: The genetic etiology of primary open-angle glaucoma (POAG) is still largely unknown, because of its complexity and disparities in its classification. This study was undertaken to determine the genetic contribution to various early, continuous markers of POAG by assessing the heritability of intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim and optic disc parameters in a genetically isolated population.

Methods: A total of 2620 subjects (mean age, 48 years; range 18-86) from extended pedigrees living in a small town in The Netherlands underwent an extensive ophthalmic examination.

Effects of inadequate anterior segment compensation on measurements with scanning laser polarimetry.

The effects of poor anterior segment compensation on scanning laser polarimetry measurements of the retinal nerve fiber layer (RNFL) were systematically explored. A prototype scanning laser polarimeter with an adjustable compensator to neutralize anterior segment birefringence was used. By systematically varying the magnitude and axis of anterior segment compensation in a healthy and a glaucomatous eye, marked changes were observed in RNFL appearance: the healthy eye could appear to have glaucomatous damage, whereas the glaucomatous eye could appear to have a thicker and healthier RNFL.