Abstract：
BACKGROUND: The associations between sleep patterns or behaviors and the risk of cirrhosis and the influence of genetic susceptibility on these associations among NAFLD participants remain inadequately elucidated.
METHODS: This study conducted a prospective follow-up of 112,196 NAFLD participants diagnosed at baseline from the UK Biobank cohort study. Five sleep behaviors were collected to measure a healthy sleep score. Five genetic variants were used to construct a polygenic risk score. We used Cox proportional hazard model to assess hazard ratios (HR) and 95% confidence intervals (CIs) for incidence of cirrhosis.
RESULTS: During the follow-up, 592 incident cirrhosis cases were documented. Healthy sleep pattern was associated with reduced risk of cirrhosis in a dose-response manner (ptrend < 0.001). Participants with favourable sleep score (versus unfavourable sleep score) had an HR of 0.55 for cirrhosis risk (95% CI 0.39-0.78). Multivariable-adjusted HRs (95% CIs) of cirrhosis incidence for NAFLDs with no frequent insomnia, sleeping for 7-8 h per day, and no excessive daytime dozing behaviors were 0.73 (0.61-0.87), 0.79 (0.66-0.93), and 0.69 (0.50-0.95), respectively. Compared with participants with favourable sleep pattern and low genetic risk, those with unfavourable sleep pattern and high genetic risk had higher risks of cirrhosis incidence (HR 3.16, 95% CI 1.88-5.33). In addition, a significant interaction between chronotype and genetic risk was detected for the incidence of cirrhosis (p for multiplicative interaction = 0.004).
CONCLUSIONS: An association was observed between healthy sleep pattern and decreased risk of cirrhosis among NAFLD participants, regardless of low or high genetic risk.
METHODS: This study conducted a prospective follow-up of 112,196 NAFLD participants diagnosed at baseline from the UK Biobank cohort study. Five sleep behaviors were collected to measure a healthy sleep score. Five genetic variants were used to construct a polygenic risk score. We used Cox proportional hazard model to assess hazard ratios (HR) and 95% confidence intervals (CIs) for incidence of cirrhosis.
RESULTS: During the follow-up, 592 incident cirrhosis cases were documented. Healthy sleep pattern was associated with reduced risk of cirrhosis in a dose-response manner (ptrend < 0.001). Participants with favourable sleep score (versus unfavourable sleep score) had an HR of 0.55 for cirrhosis risk (95% CI 0.39-0.78). Multivariable-adjusted HRs (95% CIs) of cirrhosis incidence for NAFLDs with no frequent insomnia, sleeping for 7-8 h per day, and no excessive daytime dozing behaviors were 0.73 (0.61-0.87), 0.79 (0.66-0.93), and 0.69 (0.50-0.95), respectively. Compared with participants with favourable sleep pattern and low genetic risk, those with unfavourable sleep pattern and high genetic risk had higher risks of cirrhosis incidence (HR 3.16, 95% CI 1.88-5.33). In addition, a significant interaction between chronotype and genetic risk was detected for the incidence of cirrhosis (p for multiplicative interaction = 0.004).
CONCLUSIONS: An association was observed between healthy sleep pattern and decreased risk of cirrhosis among NAFLD participants, regardless of low or high genetic risk.
摘要：
背景：睡眠模式或行为与肝硬化风险之间的关联以及遗传易感性对NAFLD参与者之间这些关联的影响仍未充分阐明。
方法：本研究对英国生物库队列研究中基线诊断的112,196名NAFLD参与者进行了前瞻性随访。收集五种睡眠行为以测量健康睡眠评分。使用五种遗传变异来构建多基因风险评分。我们使用Cox比例风险模型来评估肝硬化发生率的风险比（HR）和95％置信区间（CI）。
结果：在随访期间，记录了592例肝硬化事件。健康的睡眠模式与以剂量反应方式降低肝硬化风险相关（ptrend<0.001）。具有良好睡眠评分（与不利的睡眠评分）的参与者对于肝硬化风险的HR为0.55（95％CI0.39-0.78）。无频繁失眠的NAFLD肝硬化发生率的多变量校正HR(95%CI)，每天睡7-8小时，白天没有过度打瞌睡行为为0.73（0.61-0.87），0.79（0.66-0.93），和0.69（0.50-0.95），分别。与具有良好睡眠模式和低遗传风险的参与者相比，睡眠模式不良且遗传风险高的患者发生肝硬化的风险较高(HR3.16,95%CI1.88-5.33).此外,在肝硬化的发病率中,我们检测到时间型和遗传风险之间存在显著的交互作用(乘法交互作用p=0.004).
结论：在NAFLD参与者中，观察到健康的睡眠模式与肝硬化风险降低之间存在关联，无论遗传风险低或高。
方法：本研究对英国生物库队列研究中基线诊断的112,196名NAFLD参与者进行了前瞻性随访。收集五种睡眠行为以测量健康睡眠评分。使用五种遗传变异来构建多基因风险评分。我们使用Cox比例风险模型来评估肝硬化发生率的风险比（HR）和95％置信区间（CI）。
结果：在随访期间，记录了592例肝硬化事件。健康的睡眠模式与以剂量反应方式降低肝硬化风险相关（ptrend<0.001）。具有良好睡眠评分（与不利的睡眠评分）的参与者对于肝硬化风险的HR为0.55（95％CI0.39-0.78）。无频繁失眠的NAFLD肝硬化发生率的多变量校正HR(95%CI)，每天睡7-8小时，白天没有过度打瞌睡行为为0.73（0.61-0.87），0.79（0.66-0.93），和0.69（0.50-0.95），分别。与具有良好睡眠模式和低遗传风险的参与者相比，睡眠模式不良且遗传风险高的患者发生肝硬化的风险较高(HR3.16,95%CI1.88-5.33).此外,在肝硬化的发病率中,我们检测到时间型和遗传风险之间存在显著的交互作用(乘法交互作用p=0.004).
结论：在NAFLD参与者中，观察到健康的睡眠模式与肝硬化风险降低之间存在关联，无论遗传风险低或高。
