Fan Hong, Liu Zhenqiu, Zhang Xin, Yuan Huangbo, Zhao Xiaolan, Zhao Renjia, Shi Tingting, Wu Sheng, Xu Yiyun, Suo Chen, Chen Xingdong, Zhang Tiejun
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.
Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.
Front Genet. 2022 May 17;13:792558. doi: 10.3389/fgene.2022.792558. eCollection 2022.
Aberrant sleep parameters are associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, existing information is inconsistent among studies and involves reverse causation. Therefore, we aimed to investigate the observational associations and causations between sleep traits and NAFLD. We performed multivariable regression to assess observational associations of seven sleep traits (sleep duration, easiness of getting up in the morning, chronotype, nap during day, snoring, insomnia, and narcolepsy), and NAFLD in the UK Biobank (1,029 NAFLD). The Cox proportional hazards model was applied to derive hazard ratios and 95% confidence intervals (CIs). Furthermore, a bidirectional two-sample Mendelian randomization (MR) approach was used to explore the causal relationships between sleep traits and NAFLD. In the multivariable regression model adjusted for potential confounders, getting up in the morning not at all easy (HR, 1.51; 95% CI, 1.27-1.78) and usually insomnia (HR, 1.46; 95% CI, 1.21-1.75) were associated with the risk of NAFLD. Furthermore, the easiness of getting up in the morning and insomnia showed a dose-response association with NAFLD (P <0.05). MR analysis found consistent causal effects of NAFLD on easiness of getting up in the morning (OR, 0.995; 95% CI, 0.990-0.999; = 0.033) and insomnia (OR, 1.006; 95% CI, 1.001-1.011; = 0.024). These results were robust to weak instrument bias, pleiotropy, and heterogeneity. Findings showed consistent evidence of observational analyses and MR analyses that trouble getting up in the morning and insomnia were associated with an increased risk of NAFLD. Bidirectional MR demonstrated causal effects of NAFLD on sleep traits.
异常的睡眠参数与非酒精性脂肪性肝病（NAFLD）的风险相关。然而，现有研究信息并不一致，且存在反向因果关系。因此，我们旨在研究睡眠特征与NAFLD之间的观察性关联及因果关系。我们进行了多变量回归分析，以评估英国生物银行中7种睡眠特征（睡眠时间、早晨起床难易程度、生物钟类型、白天小睡、打鼾、失眠和发作性睡病）与NAFLD（1029例NAFLD患者）之间的观察性关联。应用Cox比例风险模型得出风险比和95%置信区间（CIs）。此外，采用双向两样本孟德尔随机化（MR）方法探讨睡眠特征与NAFLD之间的因果关系。在针对潜在混杂因素进行调整的多变量回归模型中，早晨完全不容易起床（HR，1.51；95%CI，1.27 - 1.78）和经常失眠（HR，1.46；95%CI，1.21 - 1.75）与NAFLD风险相关。此外，早晨起床难易程度和失眠与NAFLD呈剂量反应关系（P <0.05）。MR分析发现NAFLD对早晨起床难易程度（OR，0.995；95%CI，0.990 - 0.999；P = 0.033）和失眠（OR，1.006；95%CI，1.001 - 1.011；P = 0.024）存在一致的因果效应。这些结果在弱工具偏倚、多效性和异质性方面具有稳健性。研究结果表明，观察性分析和MR分析均一致证明，早晨起床困难和失眠与NAFLD风险增加相关。双向MR证明了NAFLD对睡眠特征的因果效应。
