https://orcid.org/0000-0003-2621-3939
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Abstract
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.
Data Sharing Statement
The data used in our Mendelian randomization analysis were obtained from the UK Biobank and the MRC IEU Open GWAS Project. We also acknowledge the participants and investigators of the FinnGen Study. Further inquiries can be directed to the corresponding author.
Ethics Approval
The present study was strictly conducted in accordance with the Declaration of Helsinki and International Ethical Guidelines for Health-related Research Involving Humans. This study was approved by the Medical Ethics Committee of Renmin Hospital of Wuhan University. Additional ethics approval or participate informed consent have been obtained in the original studies.
Acknowledgments
The authors thank all the investigators of the UK Biobank and the MRC IEU Open GWAS Project for publicly providing data.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare that they have no conflict of interest.