Is Genetic Risk for Sleep Apnea Causally Linked With Glaucoma Susceptibility?

Ingold, Nathan; Campos, Adrián I.; Han, Xikun; Ong, Jue‐Sheng; Gharahkhani, Puya; Mackey, David A.; Rentería, Miguel E.; Law, Matthew H.; MacGregor, Stuart

doi:10.1167/iovs.63.1.25

Cited by 4 publications

(7 citation statements)

References 40 publications

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“… 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. After adjusting for these confounding factors, the previously identified MR associations were retained, which suggested that confounding factors did not drive the observed estimate between sleep traits and POAG.…”

Section: Discussionsupporting

confidence: 87%

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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Section: Discussionsupporting

confidence: 87%

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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“…We measured the strength of the instrumental SNPs by calculating the F statistic as previously described ( 16 ); it is widely accepted that an F -statistics >10 makes weak instrument bias unlikely ( 17 ). We investigated the genetically predicted effects of CD on cardiovascular disease risk using the inverse variance weighted method.…”

Section: Methodsmentioning

confidence: 99%

Assessment of the causal association between celiac disease and cardiovascular diseases

Huang

2022

Front. Cardiovasc. Med.

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BackgroundEpidemiological studies have reported inconsistent results of the association between celiac disease (CD) and cardiovascular diseases. Moreover, the causality remains largely unknown. Therefore, we aimed to investigate whether CD is causally associated cardiovascular diseases, including ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, myocardial infarction, angina, heart failure, atrial fibrillation, and venous thromboembolism using an mendelian randomization (MR) approach.MethodsSummary-level data for CD were derived from a large-sample genome-wide association study (GWAS) including 12,041 CD cases and 12,228 controls of European ancestry. The corresponding data for ischemic stroke (34,217 cases and 406,111 controls), large artery stroke (4,373 cases and 406,111 controls), cardioembolic stroke (7,193 cases and 406,111 controls), small vessel stroke (5,386 cases and 192,662 controls), coronary heart disease (22,233 cases and 64,762 controls), myocardial infarction (11,622 cases and 187,840 controls), angina (18,168 cases and 187,840 controls), heart failure (47,309 cases and 930,014 controls), atrial fibrillation (60,620 cases and 970,216 controls), and venous thromboembolism (9,176 cases and 209,616 controls) were obtained from the IEU GWAS database. We calculated the causal effect using the inverse variance weighted method. Sensitivity analyses and leave-one-out analyses were performed to ensure the consistency and robustness of causal estimates.ResultsThe MR inverse variance weighted estimates indicated no causal effect of genetically predicted CD on ischemic stroke (OR = 1.001, 95% CI: 0.984-1.018), large artery stroke (OR = 1.003, 95% CI: 0.961-1.048), cardioembolic stroke (OR = 1.009, 95% CI: 0.977-1.042), small vessel stroke (OR = 1.023, 95% CI: 0.981-1.066), coronary heart disease (OR = 0.995, 95% CI: 0.977-1.013), myocardial infarction (OR = 0.994, 95% CI: 0.959-1.030), angina (OR = 1.006, 95% CI: 0.981-1.032), heart failure (OR = 0.999, 95% CI: 0.982-1.016), atrial fibrillation (OR = 1.000, 95% CI: 0.990-1.011), and venous thromboembolism (OR = 1.001, 95% CI: 0.971-1.032). Sensitivity analyses using the MR-Egger, weighted median, and simple mode methods yielded similar results. No evidence of horizontal pleiotropy was identified (MR Pleiotropy Residual Sum and Outlier global test and MR-Egger intercept with P > 0.05).ConclusionOur findings do not support a causal contribution of CD itself to ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, myocardial infarction, angina, heart failure, atrial fibrillation, and venous thromboembolism risk.

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“…While in prospective cohort studies a consistent observational association has been found between sleep apnea and glaucoma risk, 30 in Mendelian Randomization analyses using genetic data on a large cohort to investigate the association between genetically predicted sleep apnea and glaucoma susceptibility, no causal association was found. 31 The relationship between sleep behavior and glaucoma has also been investigated. In a study on 409,053 participants from the UK Biobank, snoring, daytime sleepiness, insomnia, short/long sleep duration, but not a late chronotype sleep pattern were associated with increased risk of glaucoma compared to healthy sleep pattern, 32 thus suggesting the importance of sleep behavior as a modifiable risk factor for glaucoma.…”

Section: Sleep Apnea and Sleep Behaviormentioning

confidence: 99%

Section: Lifestyle/modifiable Risk Factors For Glaucomamentioning

confidence: 99%

“…One great advantage of the UK Biobank is that it includes detailed eye measurements recorded for over 100,000 participants, including intraocular pressure (IOP) determined with the Ocular Response Analyzer and macula region inner retinal thickness values assessed with OCT. The UK Biobank allowed over the years multiple milestone discoveries in the field of glaucoma, including the role of genetics and behavioral risk factors, [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] that have been discussed extensively during the Think Tank and will be summarized in detail later in the manuscript. For example, results from the UK Biobank provided insights on the determinants of IOP, the major known risk factor for glaucoma onset and progression: in a cross-sectional study on 110,573 subjects, systolic BP was found to have the strongest association with IOP (partial R 2 : Goldmann-correlated IOPg: 2.30%; corneal-compensated IOPcc: 2.26%).…”

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confidence: 99%

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Lessons From The Glaucoma Foundation Think Tank 2023: A Patient-Centric Approach to Glaucoma

Harris,

Verticchio Vercellin,

Weinreb

et al. 2023

Journal of Glaucoma

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Purpose: To summarize the main topics discussed during the 28th Annual Glaucoma Foundation Think Tank Meeting “A Patient-Centric Approach to Glaucoma” held in New York on June 9th and 10th 2023. Methods: The highlights of the sessions on BIG DATA, genetics, modifiable lifestyle risk factors, female sex hormones, and neuroprotection in the field of primary open-angle glaucoma (POAG) were summarized. Results: The researchers discussed the importance of BIG DATA repositories available at national and international levels for POAG research, including the United Kingdom Biobank. Combining genotyped large cohorts worldwide, facilitated by artificial intelligence (AI) and machine learning approaches, led to the milestone discovery of 312 genome-wide significant disease loci for POAG. While these loci could be combined into a polygenic risk score with clinical utility, Think Tank meeting participants also provided analytical epidemiological evidence that behavioral risk factors modify POAG polygenetic risk, citing specific examples related to caffeine and alcohol use. The impact of female sex hormones on POAG pathophysiology was discussed, as was neuroprotection and the potential use of AI to help mitigate specific challenges faced in clinical trials and speed approval of neuroprotective agents. Conclusion: The experts agreed on the importance of genetics in defining individual POAG risk and highlighted the additional crucial role of lifestyle, gender, blood pressure, and vascular risk factors. The main takeaways also included that BIG DATA repositories and AI are important combinatory tools to foster novel strategies to prevent and stabilize glaucoma and, in the future, recover vision loss from the disease.

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Is Genetic Risk for Sleep Apnea Causally Linked With Glaucoma Susceptibility?

Cited by 4 publications

References 40 publications

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

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

Assessment of the causal association between celiac disease and cardiovascular diseases

Lessons From The Glaucoma Foundation Think Tank 2023: A Patient-Centric Approach to Glaucoma

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