Zhang Jun, Chen Xiaoyan, Zhu Yan, Wan Shanshan, Hu Shuqiong, Yang Yanning
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
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.
Nat Sci Sleep. 2024 Feb 15;16:143-153. doi: 10.2147/NSS.S439274. eCollection 2024.
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.
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.
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; OR = 1.66, 95% CI:1.18-2.34, P = 3.38×10, 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).
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.
尽管之前已有关于与原发性开角型青光眼（POAG）相关的睡眠行为的研究，但因果关系仍不明确。我们当前研究的目的是使用两样本双向孟德尔随机化（MR）方法来研究基因预测的睡眠特征与POAG之间的关系。
从公开的欧洲血统全基因组关联研究（GWAS）中收集的汇总水平数据用于双向MR分析。经过质量控制步骤后，选择了八种睡眠行为和POAG的独立单核苷酸多态性作为遗传工具。采用逆方差加权（IVW）方法作为主要方法，并辅以一系列敏感性分析，通过估计异质性和多效性来评估结果的稳健性。在调整了几个混杂因素后，使用多变量MR（MVMR）来评估睡眠特征对POAG的直接影响。
我们的研究使用IVW方法揭示了基因预测的早晨起床容易程度和睡眠时间与POAG之间存在正相关（优势比（OR）=1.78，95%置信区间（CI）：1.29 - 2.46，P = 4.33×10；OR = 1.66，95% CI：1.18 - 2.34，P = 3.38×10，分别）。其他补充MR方法也证实了类似结果。此外，MVMR结果还显示，在调整了体重指数、吸烟、饮酒和教育程度后，这两种睡眠特征对POAG的不利影响仍然存在（所有P < 0.05）。相反，在反向MR估计中，POAG的遗传易感性与不同睡眠行为之间的关系无统计学意义（所有P > 0.05）。
我们的研究表明，在欧洲人群中，基因预测的早晨容易起床或睡眠时间与POAG风险较高相关，但反之则不然。需要进一步验证和临床干预，以提供预防和管理POAG的潜在策略。
