Table1_The impact of sleep problems on cerebral aneurysm risk is mediated by hypertension: a mediated Mendelian randomization study.DOCX

IntroductionCerebral aneurysm (CA) is a common vascular disease. The risk factors of CA include hypertension, smoking, and a family history of genetic predisposition. Although sleep-related problems have been found to have a strong association with cardiovascular disease, there is a lack of research regarding the causal relationship with cerebral aneurysms.
MethodsIn this study, we investigated the causal relationship between four sleep-related problems, including snoring, insomnia, narcolepsy, and napping during the day, and CA using a two-sample Mendelian randomization (MR) analysis. Moreover, the potential confounders before sleep problems and CA were further analyzed by multivariate MR (MVMR).
ResultsThe causal relationship between insomnia and CA was obtained analytically by means of six MR analyses. There was a strong causal effect relationship between insomnia and CA, which suggests this as a potential risk factor [odds ratio (OR) = 8.35, 95% confidence interval (CI) = 2.422–28.791, p = 7.772e-04]. On this basis, hypertension was identified as a mediator between insomnia and CA by MVMR, with a mediating effect of 52.538% (OR = 3.05, 95% CI = 1.549–4.55, p = 0.015).
ConclusionThe causal relationship between insomnia and CA was predicted using genetic variance data, and insomnia was found to be a potential risk factor. Furthermore, hypertension is a mediator between insomnia and CA. Therefore, focusing on sleep problems and improving sleep quality may be an active and effective strategy to prevent CA.

引言：颅内动脉瘤（Cerebral Aneurysm, CA）是一种常见的血管疾病，其危险因素包括高血压、吸烟及遗传易感家族史。尽管已有研究证实睡眠相关问题与心血管疾病存在显著关联，但目前针对其与颅内动脉瘤的因果关系的研究仍较为匮乏。
方法：本研究采用双样本孟德尔随机化（Two-sample Mendelian Randomization, MR）分析方法，探究打鼾、失眠、发作性睡病及日间小睡四种睡眠相关问题与颅内动脉瘤之间的因果关系。此外，本研究还通过多变量孟德尔随机化（Multivariate MR, MVMR）分析，进一步探究了睡眠相关问题与颅内动脉瘤发生前的潜在混杂因素。
结果：通过六项孟德尔随机化分析，本研究明确了失眠与颅内动脉瘤之间的因果关系。失眠与颅内动脉瘤之间存在显著的因果效应，提示失眠可能是颅内动脉瘤的潜在危险因素[比值比（Odds Ratio, OR）=8.35，95%置信区间（Confidence Interval, CI）=2.422~28.791，p=7.772×10^-4]。在此基础上，多变量孟德尔随机化分析显示，高血压是失眠与颅内动脉瘤之间的中介变量，中介效应占比为52.538%（OR=3.05，95%CI=1.549~4.55，p=0.015）。
结论：本研究通过遗传变异数据证实了失眠与颅内动脉瘤之间的因果关系，明确失眠为颅内动脉瘤的潜在危险因素。此外，高血压是失眠与颅内动脉瘤之间的中介因子。因此，关注睡眠问题、改善睡眠质量或可成为预防颅内动脉瘤的积极有效策略。