Dataset Information

Polygenic Risk Score Is Associated With Intraocular Pressure and Improves Glaucoma Prediction in the UK Biobank Cohort.

ABSTRACT:

Purpose

Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. We constructed polygenic risk scores (PRSs) for IOP using the UK Biobank (UKB) data set to test whether the PRSs are associated with IOP and whether using them improves glaucoma prediction.

Methods

We conducted this study using 435,678 European participants from the UKB. We constructed weighted and unweighted PRSs using single nucleotide polymorphisms (SNPs) derived from the UKB data and previously reported IOP SNPs. We examined the associations of the PRSs with IOP and primary open-angle glaucoma (POAG) using linear and logistic regression, respectively. To quantify the discriminatory ability of the PRSs on POAG, we used the area under the receiver operating characteristic curve (AUC).

Results

The weighted PRS was significantly associated with IOP (P ? 10^-200), after adjusting for age and sex. The PRS explained an additional 4% of variance in IOP. The weighted PRS was also significantly associated with POAG (P = 1.8 × 10^-77). Subjects in the top quintile of the IOP PRS were 6.34 (95% confidence interval [CI]: 4.82-8.33; P = 2.1 × 10^-57) times more likely to have POAG, compared to those in the bottom category. The weighted PRS improved the discriminatory power for POAG (AUC increased by 5%, P = 6.2 × 10^-22) when added to the other covariates. The unweighted PRS exhibited similar results.

Conclusions

We determined that IOP PRSs are significantly associated with IOP and improve the prediction of POAG.

Translational relevance

PRSs help reduce the burden of glaucoma by early detection of genetically susceptible individuals.

SUBMITTER: Gao XR

PROVIDER: S-EPMC6450641 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polygenic Risk Score Is Associated With Intraocular Pressure and Improves Glaucoma Prediction in the UK Biobank Cohort.

Gao X Raymond XR Huang Hua H Kim Heejin H

Translational vision science & technology 20190404 2

<h4>Purpose</h4>Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. We constructed polygenic risk scores (PRSs) for IOP using the UK Biobank (UKB) data set to test whether the PRSs are associated with IOP and whether using them improves glaucoma prediction.<h4>Methods</h4>We conducted this study using 435,678 European participants from the UKB. We constructed weighted and unweighted PRSs using single nucleotide polymorphisms (SNPs) derived from the UKB data and previous ...[more]

PMID: 30972231

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Project description:PurposeTo describe the associations of physical and demographic factors with Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated intraocular pressure (IOPcc) in a British cohort.DesignCross-sectional study within the UK Biobank, a large-scale multisite cohort study in the United Kingdom.ParticipantsWe included 110 573 participants from the UK Biobank with intraocular pressure (IOP) measurements available. Their mean age was 57 years (range, 40-69 years); 54% were women, and 90% were white.MethodsParticipants had 1 IOP measurement made on each eye using the Ocular Response Analyzer noncontact tonometer. Linear regression models were used to assess the associations of IOP with physical and demographic factors.Main outcome measuresThe IOPg and IOPcc.ResultsThe mean IOPg was 15.72 mmHg (95% confidence interval [CI], 15.70-15.74 mmHg), and the mean IOPcc was 15.95 mmHg (15.92-15.97 mmHg). After adjusting for covariates, IOPg and IOPcc were both significantly associated with older age, male sex, higher systolic blood pressure (SBP), faster heart rate, greater myopia, self-reported glaucoma, and colder season (all P < 0.001). The strongest determinants of both IOPg and IOPcc were SBP (partial R(2): IOPg 2.30%, IOPcc 2.26%), followed by refractive error (IOPg 0.60%, IOPcc 1.04%). The following variables had different directions of association with IOPg and IOPcc: height (-0.77 mmHg/m IOPg; 1.03 mmHg/m IOPcc), smoking (0.19 mmHg IOPg, -0.35 mmHg IOPcc), self-reported diabetes (0.41 mmHg IOPg, -0.05 mmHg IOPcc), and black ethnicity (-0.80 mmHg IOPg, 0.77 mmHg IOPcc). This suggests that height, smoking, diabetes, and ethnicity are related to corneal biomechanical properties. The increase in both IOPg and IOPcc with age was greatest among those of mixed ethnicities, followed by blacks and whites. The same set of covariates explained 7.4% of the variability of IOPcc but only 5.3% of the variability of IOPg.ConclusionsThis analysis of associations with IOP in a large cohort demonstrated that some variables clearly have different associations with IOPg and IOPcc, and that these 2 measurements may reflect different biological characteristics.

Project description:PurposeWe examined the association of habitual caffeine intake with intraocular pressure (IOP) and glaucoma and whether genetic predisposition to higher IOP modified these associations. We also assessed whether genetic predisposition to higher coffee consumption was related to IOP.DesignCross-sectional study in the UK Biobank.ParticipantsWe included 121 374 participants (baseline ages, 39-73 years) with data on coffee and tea intake (collected 2006-2010) and corneal-compensated IOP measurements in 2009. In a subset of 77 906 participants with up to 5 web-based 24-hour-recall food frequency questionnaires (2009-2012), we evaluated total caffeine intake. We also assessed the same relationships with glaucoma (9286 cases and 189 763 controls).MethodsWe evaluated multivariable-adjusted associations with IOP using linear regression and with glaucoma using logistic regression. For both outcomes, we examined gene-diet interactions using a polygenic risk score (PRS) that combined the effects of 111 genetic variants associated with IOP. We also performed Mendelian randomization using 8 genetic variants associated with coffee intake to assess potential causal effects of coffee consumption on IOP.Main outcome measuresIntraocular pressure and glaucoma.ResultsMendelian randomization analysis did not support a causal effect of coffee drinking on IOP (P > 0.1). Greater caffeine intake was associated weakly with lower IOP: the highest (≥232 mg/day) versus lowest (<87 mg/day) caffeine consumption was associated with a 0.10-mmHg lower IOP (Ptrend = 0.01). However, the IOP PRS modified this association: among those in the highest IOP PRS quartile, consuming > 480 mg/day versus < 80 mg/day was associated with a 0.35-mmHg higher IOP (Pinteraction = 0.01). The relationship between caffeine intake and glaucoma was null (P ≥ 0.1). However, the IOP PRS also modified this relationship: compared with those in the lowest IOP PRS quartile consuming no caffeine, those in the highest IOP PRS quartile consuming ≥ 321 mg/day showed a 3.90-fold higher glaucoma prevalence (Pinteraction = 0.0003).ConclusionsHabitual caffeine consumption was associated weakly with lower IOP, and the association between caffeine consumption and glaucoma was null. However, among participants with the strongest genetic predisposition to elevated IOP, greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence.

Project description:ImportanceRhegmatogenous retinal detachment is a potentially sight-threatening condition. The role of myopia or intraocular pressure (IOP) in retinal detachment remains unclear.ObjectiveTo determine if myopia or IOP is associated with retinal detachment risk using genetic data.Design, setting, and participantsObservational analyses and 2-sample mendelian randomization were used to evaluate the associations between myopia, IOP, and retinal detachment risk in European descent participants from the UK Biobank (UKBB) cohort (n = 405 692). For retinal detachment, a genome-wide association study on 4257 cases and 39 181 controls in the UKBB was conducted. Genetic variants associated with mean spherical equivalent (MSE) refractive error (n = 95 827) and IOP (n = 101 939) were derived using independent participants from the retinal detachment genome-wide association study. Recruitment to the UKBB occurred between 2006 and 2010, and data analysis occurred from February 2019 to March 2020.Main outcomes and measuresThe odds ratio (OR) of retinal detachment caused by per-unit increases in MSE refractive error (in diopters [D]) and IOP (in mm Hg).ResultsOf the 405 692 participants in the UKBB cohort, the mean (SD) age was 56.87 (7.96) years, the mean (SD) MSE was -0.31 (2.65) D, the mean (SD) corneal-compensated IOP was 16.05 (3.49) mm Hg, and 4253 participants (1.0%) had retinal detachment. Genetic analyses of the 4257 cases and 39 181 controls identified 2 novel retinal detachment genes: COL22A1 (lead single-nucleotide variant rs11992725; P = 4.8 × 10-10) and FAT3 (lead single-nucleotide variant rs10765568; P = 1.2 × 10-15). Genetically assessed MSE refractive error was negatively associated with retinal detachment (per-unit [D] increase in MSE refractive error: OR, 0.72; 95% CI, 0.69-0.76; P = 3.8 × 10-44). For each 6-D decrease in MSE refractive error (representing the move of refractive error from emmetropia to high myopia), retinal detachment risk increased 7.2-fold (95% CI, 5.19-9.27). For per-unit (mm Hg) genetically assessed increase in IOP, the risk of retinal detachment increased by 8% (OR, 1.08; 95% CI, 1.03-1.14; P = .001).Conclusions and relevanceThis study provides genetic support for the assertion that myopia and IOP are associated with the risk of retinal detachment and that myopia prevention efforts may help prevent retinal detachment.

Project description:PURPOSE:To generate personalized forecasts of how patients with open-angle glaucoma (OAG) experience disease progression at different intraocular pressure (IOP) levels to aid clinicians with setting personalized target IOPs. DESIGN:Secondary analyses using longitudinal data from 2 randomized controlled trials. PARTICIPANTS:Participants with moderate or advanced OAG from the Collaborative Initial Glaucoma Treatment Study (CIGTS) or the Advanced Glaucoma Intervention Study (AGIS). METHODS:By using perimetric and tonometric data from trial participants, we developed and validated Kalman Filter (KF) models for fast-, slow-, and nonprogressing patients with OAG. The KF can generate personalized and dynamically updated forecasts of OAG progression under different target IOP levels. For each participant, we determined how mean deviation (MD) would change if the patient maintains his/her IOP at 1 of 7 levels (6, 9, 12, 15, 18, 21, or 24 mmHg) over the next 5 years. We also model and predict changes to MD over the same time horizon if IOP is increased or decreased by 3, 6, and 9 mmHg from the level attained in the trials. MAIN OUTCOME MEASURES:Personalized estimates of the change in MD under different target IOP levels. RESULTS:A total of 571 participants (mean age, 64.2 years; standard deviation, 10.9) were followed for a mean of 6.5 years (standard deviation, 2.8). Our models predicted that, on average, fast progressors would lose 2.1, 6.7, and 11.2 decibels (dB) MD under target IOPs of 6, 15, and 24 mmHg, respectively, over 5 years. In contrast, on average, slow progressors would lose 0.8, 2.1, and 4.1 dB MD under the same target IOPs and time frame. When using our tool to quantify the OAG progression dynamics for all 571 patients, we found no statistically significant differences over 5 years between progression for black versus white, male versus female, and CIGTS versus AGIS participants under different target IOPs (P > 0.05 for all). CONCLUSIONS:To our knowledge, this is the first clinical decision-making tool that generates personalized forecasts of the trajectory of OAG progression at different target IOP levels. This approach can help clinicians determine appropriate, personalized target IOPs for patients with OAG.

Dataset Information

Polygenic Risk Score Is Associated With Intraocular Pressure and Improves Glaucoma Prediction in the UK Biobank Cohort.

Purpose

Methods

Results

Conclusions

Translational relevance

Publications

Polygenic Risk Score Is Associated With Intraocular Pressure and Improves Glaucoma Prediction in the UK Biobank Cohort.

Similar Datasets

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