Obstructive sleep apnoea and glaucoma: a systematic review and meta-analysis

Cheong, Alex Jia Yang; Wang, Sean Kang Xuan; Woon, Chang Yi; Yap, Ki Han; Ng, Kevin Joo Yang; Xu, Flora Wen Xin; Alkan, Uri; Ng, Adele Chin Wei; See, Anna; Loh, Shaun; Aung, Tin; Toh, Song Tar

doi:10.1038/s41433-023-02471-6

Cited by 10 publications

(5 citation statements)

References 70 publications

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“…In contrast to the results of a PRS-based PheWAS, our investigation using PheWAS with POAG diagnosis as the independent variable revealed significant associations with various systemic conditions, which were previously identified as systemic risk factors for glaucoma in epidemiologic studies [ 7 , 35 – 39 ]. Despite the distinct disease associations of POAG, we found no positive associations between genetic liability for POAG and systemic disease phenotypes.…”

Section: Discussioncontrasting

confidence: 99%

Polygenic risk score-based phenome-wide association for glaucoma and its impact on disease susceptibility in two large biobanks

Yun,

Jung,

Lee

et al. 2024

J Transl Med

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Background Glaucoma is a leading cause of worldwide irreversible blindness. Considerable uncertainty remains regarding the association between a variety of phenotypes and the genetic risk of glaucoma, as well as the impact they exert on the glaucoma development. Methods We investigated the associations of genetic liability for primary open angle glaucoma (POAG) with a wide range of potential risk factors and to assess its impact on the risk of incident glaucoma. The phenome-wide association study (PheWAS) approach was applied to determine the association of POAG polygenic risk score (PRS) with a wide range of phenotypes in 377, 852 participants from the UK Biobank study and 43,623 participants from the Penn Medicine Biobank study, all of European ancestry. Participants were stratified into four risk tiers: low, intermediate, high, and very high-risk. Cox proportional hazard models assessed the relationship of POAG PRS and ocular factors with new glaucoma events. Results In both discovery and replication set in the PheWAS, a higher genetic predisposition to POAG was specifically correlated with ocular disease phenotypes. The POAG PRS exhibited correlations with low corneal hysteresis, refractive error, and ocular hypertension, demonstrating a strong association with the onset of glaucoma. Individuals carrying a high genetic burden exhibited a 9.20-fold, 11.88-fold, and 28.85-fold increase in glaucoma incidence when associated with low corneal hysteresis, high myopia, and elevated intraocular pressure, respectively. Conclusion Genetic susceptibility to POAG primarily influences ocular conditions, with limited systemic associations. Notably, the baseline polygenic risk for POAG robustly associates with new glaucoma events, revealing a large combined effect of genetic and ocular risk factors on glaucoma incidents.

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Section: Discussioncontrasting

confidence: 99%

Polygenic risk score-based phenome-wide association for glaucoma and its impact on disease susceptibility in two large biobanks

Yun,

Jung,

Lee

et al. 2024

J Transl Med

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“…However, this hypothesis requires further verification. Patients with obstructive sleep apnea (OSA) have a higher risk of POAG compared to those without OSA, 59 , 60 and it is believed that oxidative stress plays a significant role. 61 Therefore, it is equally unlikely that diet-derived antioxidants can be protective against POAG related to OSA.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Causality Between Diet-Derived Antioxidants and Primary Open-Angle Glaucoma: A Mendelian Randomization Study

Xiong,

Zhang,

Mao

et al. 2024

Trans. Vis. Sci. Tech.

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Purpose This study aimed to investigate the genetic causal relationships among diet-derived circulating antioxidants, primary open-angle glaucoma (POAG), and glaucoma-related traits using two-sample Mendelian randomization (MR). Methods Genetic variants associated with diet-derived circulating antioxidants (retinol, ascorbate, β-carotene, lycopene, α-tocopherol, and γ-tocopherol) were assessed as absolute and metabolic instrumental variables. POAG and glaucoma-related traits data were derived from a large, recently published genome-wide association study database; these traits included intraocular pressure (IOP), macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell–inner plexiform layer (mGCIPL) thickness, and vertical cup-to-disc ratio (vCDR). MR analyses were performed per outcome for each exposure. Results We found no causal association between six diet-derived antioxidants and POAG using the International Glaucoma Genetics Consortium data. For absolute antioxidants, the odds ratios (ORs) ranged from 1.011 (95% confidence interval [CI], 0.854–1.199; P = 0.895) per natural log‐transformed β-carotene to 1.052 (95% CI, 0.911–1.215; P = 0.490) for 1 µmol/L of ascorbate. For antioxidant metabolites, the OR ranged from 0.998 (95% CI, 0.801–1.244; P = 0.989) for ascorbate to 1.210 (95% CI, 0.870–1.682; P = 0.257) for γ-tocopherol, using log-transformed levels. A similar result was obtained with the FinnGen Biobank. Furthermore, our results showed no significant genetic association between six diet-derived antioxidants and glaucoma-related traits. Conclusions Our study did not support a causal association among six diet‐derived circulating antioxidants, POAG, and glaucoma-related traits. This suggests that the intake of antioxidants may not have a preventive effect on POAG and offers no protection to retinal nerve cells. Translational Relevance This study provides valid evidence regarding the use of diet-derived antioxidants for glaucoma patients.

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“… 48 A recently published meta-analysis suggested that OSA is associated with a higher risk of glaucoma and its subtype. 49 These inconsistent conclusions may be attributed to different risk biases, including the control of confounding factors and reverse caution. Considering the wide range of potential confounders, the findings about the causal effects of OSA on glaucoma in our MR analysis are consistent with a previous MR study conducted by Ingold Nathan et al 50 Different from their MR design, we used MVMR to avoid horizontal pleiotropy, which allowed us to further consider the influence of additional factors and draw a more solid conclusion.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Causal Relationship Between Sleep Behaviors and Primary Open-Angle Glaucoma: A Bidirectional Two-Sample Mendelian Randomization Study

Zhang,

Chen,

Zhu

et al. 2024

NSS

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Background Although previous studies of sleep-related behaviors in relation to primary open-angle glaucoma (POAG) have been noted, the causal relationship remains unclear. The purpose of our present study was to investigate the relationships of genetically predicted sleep traits with POAG using a two-sample bidirectional Mendelian randomization (MR) method. Methods Summary-level data collected from publicly available genome-wide association studies (GWAS) of European decent were applied for the bidirectional MR analysis. After quality control steps, independent single-nucleotide polymorphisms for eight sleep behaviors and POAG were selected as the genetic instruments. The inverse-variance weighted (IVW) approach was adopted as the primary method, which was complemented by a series of sensitivity analyses to assess the robustness of the results by estimating heterogeneity and pleiotropy. Multivariable MR (MVMR) was used to assess the direct effect of sleep traits on POAG, after adjusting for several confounding factors. Results Our investigation revealed a positive correlation between genetically predicted ease of getting up in the morning and sleep duration and POAG using the IVW method (odds ratio (OR)=1.78, 95% confidence interval (CI):1.29–2.46, P = 4.33× 10 −4 ; OR = 1.66, 95% CI:1.18–2.34, P = 3.38×10 −3 , respectively). Other supplementary MR methods also confirmed similar results. Moreover, the MVMR results also revealed that the adverse effects of these two sleep traits on POAG persisted after adjusting for body mass index, smoking, drinking, and education (all P < 0.05). Conversely, the relationships between genetic liability of POAG and different sleep behaviors were not statistically significant in the reverse-direction MR estimate (all P > 0.05). Conclusion Our study demonstrated that genetic prediction of getting up easily in the morning or sleep duration were associated with a higher risk of POAG, but not vice versa, in a European population. Further validation and clinical interventions are required to offer potential strategies to prevent and manage POAG.

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Obstructive sleep apnoea and glaucoma: a systematic review and meta-analysis

Cited by 10 publications

References 70 publications

Polygenic risk score-based phenome-wide association for glaucoma and its impact on disease susceptibility in two large biobanks

Polygenic risk score-based phenome-wide association for glaucoma and its impact on disease susceptibility in two large biobanks

Assessment of Causality Between Diet-Derived Antioxidants and Primary Open-Angle Glaucoma: A Mendelian Randomization Study

Investigating the Causal Relationship Between Sleep Behaviors and Primary Open-Angle Glaucoma: A Bidirectional Two-Sample Mendelian Randomization Study

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