Mendelian Randomization Implicates Bidirectional Association between Myopia and Primary Open-Angle Glaucoma or Intraocular Pressure

Chong, Rachel S.; Li, Hengtong; Cheong, Alex Jia Yang; Fan, Qiao; Koh, Victor; Nongpiur, Monisha E.; Cheng, Ching‐Yu

doi:10.1016/j.ophtha.2022.11.030

Cited by 28 publications

(22 citation statements)

References 60 publications

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“…MR analysis has been used to investigate the impact of education levels, vitamin D, or medication on myopia; and lipid levels, refractive errors, or c-reactive protein levels on age-related macular degeneration [ 44 ]. In addition, lipid levels, central corneal thickness, type 2 diabetes, and refractive errors have been evaluated as risk factors for glaucoma in MR analyses [ 45 , 46 , 47 ]. From this perspective, the impact of iritis or uveitis exposure on the development of glaucoma can be investigated through a MR research approach.…”

Section: Discussionmentioning

confidence: 99%

Causal Association between Iritis or Uveitis and Glaucoma: A Two-Sample Mendelian Randomisation Study

Seo

Lee

2023

Genes

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Recent studies have suggested an association between iritis or uveitis and glaucoma. This study investigated the causal relationship between glaucoma and iritis and uveitis as exposures in a multi-ethnic population. Single-nucleotide polymorphisms associated with exposures to iritis and uveitis from the genome-wide association study (GWAS) data of Biobank Japan (BBJ) and the meta-analysis data from BBJ and UK Biobank (UKB) were used as instrumental variables (IVs). The GWAS dataset for glaucoma was extracted from the meta-analysis data (n = 240,302) of Genetic Epidemiology Research in Adult Health and Aging and UKB. The casual estimates were assessed with a two-sample Mendelian randomisation (MR) test using the inverse-variance-weighted (IVW) method, weighted median method, MR–Egger method, and MR-Pleiotropy Residual Sum and Outlier test. The IVW method revealed a significant causal association between iritis and glaucoma using IVs (p < 5.0 × 10−8) from the East Asian population (n = 2) (odds ratio [OR] = 1.01, p = 0.017), a significant association between iritis exposures (p < 5.0 × 10−8) in the multi-ethnic population (n = 11) (OR = 1.04, p = 0.001), and a significant causal association between uveitis exposures (n = 10 with p < 5.0 × 10−8) and glaucoma in the multi-ethnic population (OR = 1.04, p = 0.001). Iritis and uveitis had causal effects on glaucoma risk based on IVs from the multi-ethnic population. These findings imply that the current classifications of uveitic glaucoma and open-angle glaucoma overlap, indicating the need for further investigating these complex relationships.

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Section: Discussionmentioning

confidence: 99%

Causal Association between Iritis or Uveitis and Glaucoma: A Two-Sample Mendelian Randomisation Study

Seo

Lee

2023

Genes

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“…All regression coefficients were derived from MR instrumental analysis using IVW. In the end, Sobel’s test was applied to test the significance of the mediation effects ( Chong et al, 2022 ). The following equation was used to estimate the percentage of the impact that is mediated by any of the potential mediators ( Xu et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis

Xiao

Feng

et al. 2023

Front. Genet.

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Background: Previous observational studies have suggested that circulating adipokine concentrations are related to a greater risk of venous thromboembolism (VTE). However, it remained unclear whether these observations reflect causality.Objective: This study aimed to investigate the causal relationship between circulating adipokine concentrations (including adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN) and the risk of VTE and its subtypes (DVT and PE) and to determine whether circulating adipokine concentrations are a mediator of venous thromboembolic events in obese patients.Methods: We used Mendelian randomization (MR) analyses to determine the effects of the body mass index (BMI), adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN levels on VTE, DVT, and PE in a cohort of 11,288 VTE cases, 5,632 DVT cases, 5,130 PE cases, and 254,771 controls. We then assessed the proportion of the effect of obesity on VTE, DVT, and PE explained by circulating leptin levels.Result: Genetically predicted higher BMI was related to increased VTE (OR = 1.45, p < 0.001), DVT (OR = 1.63, p < 0.001), and PE (OR = 1.37, p < 0.001) risk, and higher circulating leptin levels increase odds of VTE (OR = 1.96, q < 0.001), DVT (OR = 2.52, q < 0.001), and PE (OR = 2.26, q = 0.005). In addition, we found that the causal effect between elevated serum adiponectin and the decreased risk of VTE (OR = 0.85, p = 0.013, q = 0.053) and PE (OR = 0.81, p = 0.032, q = 0.083) and between MCP-1 and the reduced risk of VTE (OR = 0.88, p = 0.048, q = 0.143) is no longer significant after FDR adjustment. In MR mediation analysis, the mediation effect of circulating leptin levels in the causal pathway from BMI to PE was estimated to be 1.28 (0.95–1.71, p = 0.10), accounting for 39.14% of the total effect.Conclusion: The circulating leptin level is a risk factor for VTE, DVT, and PE, but it might be a potential mediator of BMI on the risk of PE, and thus, interventions on the circulating leptin level in obesity might reduce the risk of PE. Adiponectin is a potential protective factor for both VTE and PE.

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“…Recent genetic research has also implicated IOP as a key mediator in the causal pathway between myopia and POAG [ 54 ]. Mendelian randomization (MR) analyses have found bidirectional genetic causal associations between myopia and POAG as well as IOP, suggesting the possibility of a converse directional relationship [ 54 ]. Additionally, multivariate genomic structural modeling suggests that the causal effect of myopia on POAG is predominantly mediated by IOP [ 54 ].…”

Section: Diagnostic Challengesmentioning

confidence: 99%

“…Mendelian randomization (MR) analyses have found bidirectional genetic causal associations between myopia and POAG as well as IOP, suggesting the possibility of a converse directional relationship [ 54 ]. Additionally, multivariate genomic structural modeling suggests that the causal effect of myopia on POAG is predominantly mediated by IOP [ 54 ]. Other MR analyses have also reported genetic correlations between POAG and myopia [ 54 , 55 ].…”

Section: Diagnostic Challengesmentioning

confidence: 99%

“…Additionally, multivariate genomic structural modeling suggests that the causal effect of myopia on POAG is predominantly mediated by IOP [ 54 ]. Other MR analyses have also reported genetic correlations between POAG and myopia [ 54 , 55 ]. These associations, however, did not reach statistical significance in Asian eyes, suggesting that myopia-related glaucoma in Asian eyes may also involve IOP-independent mechanisms such as ethnic differences in blood pressure variability.…”

Section: Diagnostic Challengesmentioning

confidence: 99%

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Glaucoma and Myopia: Diagnostic Challenges

et al. 2023

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The rising global prevalence of myopia is a growing concern for clinicians, as it predisposes patients to severe ocular pathologies including glaucoma. High myopia can be associated with clinical features that resemble glaucomatous damage, which make an accurate glaucoma diagnosis challenging, particularly among patients with normal intraocular pressures. These patients may also present with established visual field defects which can mimic glaucoma, and standard imaging technology is less useful in disease detection and monitoring due to the lack of normative data for these anatomically unique eyes. Progression over time remains the most critical factor in facilitating the detection of early glaucomatous changes, and thus careful longitudinal follow-up of high-risk myopic patients is the most important aspect of management. Here, we review our current understanding of the complex relationship between myopia and glaucoma, and the diagnostic challenges and limitations of current testing protocols including visual field, intraocular pressure, and imaging. Furthermore, we discuss the clinical findings of two highly myopic patients with suspected glaucoma.

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Mendelian Randomization Implicates Bidirectional Association between Myopia and Primary Open-Angle Glaucoma or Intraocular Pressure

Cited by 28 publications

References 60 publications

Causal Association between Iritis or Uveitis and Glaucoma: A Two-Sample Mendelian Randomisation Study

Causal Association between Iritis or Uveitis and Glaucoma: A Two-Sample Mendelian Randomisation Study

Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis

Glaucoma and Myopia: Diagnostic Challenges

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