Dataset Information

Genetic variants associated with optic nerve vertical cup-to-disc ratio are risk factors for primary open angle glaucoma in a US Caucasian population.

ABSTRACT: Genetically complex disorders, such as primary open angle glaucoma (POAG), may include highly heritable quantitative traits as part of the overall phenotype, and mapping genes influencing the related quantitative traits may effectively identify genetic risk factors predisposing to the complex disease. Recent studies have identified SNPs associated with optic nerve area and vertical cup-to-disc ratio (VCDR). The purpose of this study was to evaluate the association between these SNPs and POAG in a US Caucasian case-control sample.Five SNPs previously associated with optic disc area, or VCDR, were genotyped in 539 POAG cases and 336 controls. Genotype data were analyzed for single SNP associations and SNP interactions with VCDR and POAG.SNPs associated with VCDR rs1063192 (CDKN2B) and rs10483727 (SIX1/SIX6) were also associated with POAG (P = 0.0006 and P = 0.0043 for rs1063192 and rs10483727, respectively). rs1063192, associated with smaller VCDR, had a protective effect (odds ratio [OR] = 0.73; 95% confidence interval [CI], 0.58-0.90), whereas rs10483727, associated with larger VCDR, increased POAG risk (OR = 1.33; 95% CI, 1.08-1.65). POAG risk associated with increased VCDR was significantly influenced by the C allele of rs1900004 (ATOH7), associated with increased optic nerve area (P-interaction = 0.025; OR = 1.89; 95% CI, 1.22-2.94).Genetic variants influencing VCDR are associated with POAG in a US Caucasian population. Variants associated with optic nerve area are not independently associated with disease but can influence the effects of VCDR variants suggesting that increased optic disc area can significantly contribute to POAG risk when coupled with risk factors controlling VCDR.

SUBMITTER: Fan BJ

PROVIDER: S-EPMC3101676 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic variants associated with optic nerve vertical cup-to-disc ratio are risk factors for primary open angle glaucoma in a US Caucasian population.

Fan Bao Jian BJ Wang Dan Yi DY Pasquale Louis R LR Haines Jonathan L JL Wiggs Janey L JL

Investigative ophthalmology & visual science 20110328 3

<h4>Purpose</h4>Genetically complex disorders, such as primary open angle glaucoma (POAG), may include highly heritable quantitative traits as part of the overall phenotype, and mapping genes influencing the related quantitative traits may effectively identify genetic risk factors predisposing to the complex disease. Recent studies have identified SNPs associated with optic nerve area and vertical cup-to-disc ratio (VCDR). The purpose of this study was to evaluate the association between these S ...[more]

PMID: 21398277

Similar Datasets

Project description:PurposePrimary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness in the United States and worldwide. Although deep learning methods have been proposed to diagnose POAG, these methods all used a single image as input. Contrastingly, glaucoma specialists typically compare the follow-up image with the baseline image to diagnose incident glaucoma. To simulate this process, we proposed a Siamese neural network, POAGNet, to detect POAG from optic disc photographs.DesignThe POAGNet, an algorithm for glaucoma diagnosis, is developed using optic disc photographs.ParticipantsThe POAGNet was trained and evaluated on 2 data sets: (1) 37 339 optic disc photographs from 1636 Ocular Hypertension Treatment Study (OHTS) participants and (2) 3684 optic disc photographs from the Sequential fundus Images for Glaucoma (SIG) data set. Gold standard labels were obtained using reading center grades.MethodsWe proposed a Siamese network model, POAGNet, to simulate the clinical process of identifying POAG from optic disc photographs. The POAGNet consists of 2 side outputs for deep supervision and uses convolution to measure the similarity between 2 networks.Main outcome measuresThe main outcome measures are the area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity.ResultsIn POAG diagnosis, extensive experiments show that POAGNet performed better than the best state-of-the-art model on the OHTS test set (area under the curve [AUC] 0.9587 versus 0.8750). It also outperformed the baseline models on the SIG test set (AUC 0.7518 versus 0.6434). To assess the transferability of POAGNet, we also validated the impact of cross-data set variability on our model. The model trained on OHTS achieved an AUC of 0.7490 on SIG, comparable to the previous model trained on the same data set. When using the combination of SIG and OHTS for training, our model achieved superior AUC to the single-data model (AUC 0.8165 versus 0.7518). These demonstrate the relative generalizability of POAGNet.ConclusionsBy simulating the clinical grading process, POAGNet demonstrated high accuracy in POAG diagnosis. These results highlight the potential of deep learning to assist and enhance clinical POAG diagnosis. The POAGNet is publicly available on https://github.com/bionlplab/poagnet.

Project description:PurposeTo investigate whether lamina cribrosa (LC) defects are associated with optic disc morphology in primary open angle glaucoma (POAG) eyes with high myopia.MethodsA total of 129 POAG patients and 55 age-matched control subjects with high myopia were evaluated. Three-dimensional scan images obtained by swept source optical coherence tomography were used to detect LC defects. Radial B-scans and infrared images obtained by spectral domain optical coherence tomography were used to measure ?-peripapillary atrophy (PPA) lengths with and without Bruch's membrane (BM) (temporal, nasal, superior, and inferior), tilt angle (vertical and horizontal), and disc diameter (transverse and longitudinal). Peripapillary intrachoroidal cavitations (PICCs), disc area, ovality index, and cyclotorsion of the optic disc were analyzed as well.ResultsLC defects were found in 70 of 129 (54.2%) POAG eyes and 1 of 55 (1.8%) control eyes (P < 0.001). Age, sex, spherical equivalent, axial length, intraocular pressure, and central corneal thickness were not significantly different among POAG eyes with LC defects, POAG eyes without LC defects, and control eyes. Temporal PPA lengths without BM in all three groups correlated significantly with vertical and horizontal tilt angles, although no PPA length with BM correlated significantly with any tilt angle. PICCs were detected more frequently in POAG eyes with LC defects than those without LC defects (P = 0.01) and control eyes (P = 0.02). POAG eyes with LC defects showed a smaller ovality index (P = 0.004), longer temporal PPA without BM (P < 0.001), and larger vertical/horizontal tilt angles (vertical, P < 0.001; horizontal, P = 0.01), and transverse diameter (P = 0.01). In multivariate analysis for the presence of LC defects, presence of POAG (P < 0.001) and vertical tilt angle (P < 0.001) were identified as significant.ConclusionsThe presence of LC defects was associated with myopic optic disc morphology in POAG eyes with high myopia.

Dataset Information

Genetic variants associated with optic nerve vertical cup-to-disc ratio are risk factors for primary open angle glaucoma in a US Caucasian population.

Publications

Genetic variants associated with optic nerve vertical cup-to-disc ratio are risk factors for primary open angle glaucoma in a US Caucasian population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets