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

Jun Zhang; Xiaoyan Chen; Yan Zhu; Shanshan Wan; Shuqiong Hu; Yanning Yang

doi:10.2147/NSS.S439274

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

Nat Sci Sleep. 2024 Feb 15:16:143-153. doi: 10.2147/NSS.S439274. eCollection 2024.

Authors

Jun Zhang^#¹, Xiaoyan Chen^#², Yan Zhu^#¹, Shanshan Wan¹, Shuqiong Hu³, Yanning Yang¹

Affiliations

¹ Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
² Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, People's Republic of China.
³ Aier Eye Hospital of Wuhan University (Wuhan Aier Eye Hospital), Wuhan, Hubei, People's Republic of China.

^# Contributed equally.

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.

Keywords: genome-wide association study; mendelian randomization; primary open-angle glaucoma; risk factors; sleep behaviors.

Grants and funding

This work was supported by Fundamental Research Funds for Central Universities (2042023kf0047); National Natural Science Foundation of China (82301193); and Hubei Provincial Natural Science Foundation of China (2023AFB223).