Chen Xi, Liu Shiji, Liu Chang, Huang Yuke, Hou Xiangtao, Zhuang Jiejie, Luo Yiqi, Yu Na, Zhuang Jing, Yu Keming
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Tianhe District, Guangzhou, China.
Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China ; and.
Cornea. 2025 Feb 1;44(2):221-225. doi: 10.1097/ICO.0000000000003741.
To clarify the controversial causal association between snoring and keratoconus (KCN), which is crucial in clinical prevention and treatment.
This is a 2-sample bidirectional mendelian randomization (MR) case-control study. MR is an innovative method that uses genetic variation as a natural experiment to investigate the causal relationships between potentially modifiable risk factors and health outcomes in observational data. The single nucleotide polymorphisms associated with snoring were retrieved from the UK biobank cohort with 218,346 participants (61,792 cases and 156,554 controls). The summary statistics of KCN were obtained from the European ancestry with 209,598 subjects (311 cases and 209,287 controls). The inverse-variance-weighted method was applied as the primary estimate, whereas weighted median and MR-pleiotropy residual sum and outlier played a subsidiary role.
Elevated risk of snoring showed a robust causal effect on KCN (inverse-variance-weighted: causal effect = 9.821, 95% confidence interval [CI], 1.944-17.699, P = 0.015), which was consistent with complementary methods of the weighted median (causal effect = 11.117, 95% CI, 2.603-19.631, P = 0.010), maximum likelihood (causal effect = 10.245, 95% CI, 3.967-16.523, P = 0.001), and MR-pleiotropy residual sum and outlier (causal effect = 9.793, 95% CI, 2.316-17.269, P = 0.028). However, there was no causality of KCN on the increasing risk of snoring.
This study provides genetic evidence supporting the causal role of snoring on KCN. Our findings provide new insights into potential strategies to manage KCN.
阐明打鼾与圆锥角膜（KCN）之间存在争议的因果关系，这在临床预防和治疗中至关重要。
这是一项两样本双向孟德尔随机化（MR）病例对照研究。MR是一种创新方法，它利用基因变异作为自然实验，在观察性数据中研究潜在可改变的风险因素与健康结果之间的因果关系。从英国生物银行队列中检索出与打鼾相关的单核苷酸多态性，该队列有218346名参与者（61792例病例和156554例对照）。KCN的汇总统计数据来自欧洲血统的209598名受试者（311例病例和209287例对照）。采用逆方差加权法作为主要估计方法，而加权中位数和MR多效性残差总和及异常值法起辅助作用。
打鼾风险升高对KCN显示出强烈的因果效应（逆方差加权法：因果效应=9.821，95%置信区间[CI]，1.944 - 17.699，P = 0.015），这与加权中位数（因果效应=11.117，95% CI，2.603 - 19.631，P = 0.010）、最大似然法（因果效应=10.245，95% CI，3.967 - 16.523，P = 0.001）以及MR多效性残差总和及异常值法（因果效应=9.793，95% CI，2.316 - 17.269，P = 0.028）的互补方法一致。然而，KCN对打鼾风险增加不存在因果关系。
本研究提供了基因证据支持打鼾对KCN的因果作用。我们的研究结果为圆锥角膜潜在管理策略提供了新见解。
