Synopsis of Golden Chamber Department, Chinese Medicine College, Beijing University of Chinese Medicine, Beijing, China.
Front Endocrinol (Lausanne). 2023 Jun 2;14:1159258. doi: 10.3389/fendo.2023.1159258. eCollection 2023.
Non-alcoholic fatty liver disease(NAFLD) is common worldwide and has previously been reported to be associated with sleep traits. However, it is not clear whether NAFLD changes sleep traits or whether the changes in sleep traits lead to the onset of NAFLD. The purpose of this study was to investigate the causal relationship between NAFLD and changes in sleep traits using Mendelian randomization.
We proposed a bidirectional Mendelian randomization (MR) analysis and performed validation analyses to dissect the association between NAFLD and sleep traits. Genetic instruments were used as proxies for NAFLD and sleep. Data of genome-wide association study(GWAS) were obtained from the center for neurogenomics and cognitive research database, Open GWAS database and GWAS catalog. Three MR methods were performed, including inverse variance weighted method(IVW), MR-Egger, weighted median.
In total,7 traits associated with sleep and 4 traits associated with NAFLD are used in this study. A total of six results showed significant differences. Insomnia was associated with NAFLD (OR(95% CI)= 2.25(1.18,4.27), P = 0.01), Alanine transaminase levels (OR(95% CI)= 2.79(1.70, 4.56), P =4.71×10-5) and percent liver fat(OR(95% CI)= 1.31(1.03,1.69), P = 0.03). Snoring was associated with percent liver fat (1.15(1.05,1.26), P =2×10-3), alanine transaminase levels (OR(95% CI)= 1.27(1.08,1.50), P =0.04).And dozing was associated with percent liver fat(1.14(1.02,1.26), P =0.02).For the remaining 50 outcomes, no significant or definitive association was yielded in MR analysis.
Genetic evidence suggests putative causal relationships between NAFLD and a set of sleep traits, indicating that sleep traits deserves high priority in clinical practice. Not only the confirmed sleep apnea syndrome, but also the sleep duration and sleep state (such as insomnia) deserve clinical attention. Our study proves that the causal relationship between sleep characteristics and NAFLD is the cause of the change of sleep characteristics, while the onset of non-NAFLD is the cause of the change of sleep characteristics, and the causal relationship is one-way.
非酒精性脂肪性肝病（NAFLD）在全球范围内较为常见，此前有报道称其与睡眠特征有关。然而，目前尚不清楚是 NAFLD 改变了睡眠特征，还是睡眠特征的改变导致了 NAFLD 的发生。本研究旨在采用孟德尔随机化（MR）来探讨 NAFLD 与睡眠特征变化之间的因果关系。
我们提出了一种双向孟德尔随机化（MR）分析，并进行了验证分析，以剖析 NAFLD 与睡眠特征之间的关联。遗传工具被用作 NAFLD 和睡眠的替代物。全基因组关联研究（GWAS）的数据来自神经基因组学和认知研究中心数据库、开放 GWAS 数据库和 GWAS 目录。我们进行了三种 MR 方法，包括逆方差加权法（IVW）、MR-Egger 和加权中位数。
本研究共使用了与睡眠相关的 7 种特征和与 NAFLD 相关的 4 种特征。共有 6 项结果显示出显著差异。失眠与 NAFLD 相关（OR（95%CI）=2.25（1.18，4.27），P=0.01）、丙氨酸氨基转移酶水平（OR（95%CI）=2.79（1.70，4.56），P=4.71×10-5）和肝脂肪百分比（OR（95%CI）=1.31（1.03，1.69），P=0.03）。打鼾与肝脂肪百分比（1.15（1.05，1.26），P=2×10-3）、丙氨酸氨基转移酶水平（OR（95%CI）=1.27（1.08，1.50），P=0.04）相关。而嗜睡与肝脂肪百分比（1.14（1.02，1.26），P=0.02）相关。对于其余 50 个结果，MR 分析未得出显著或明确的关联。
遗传证据表明，NAFLD 与一系列睡眠特征之间存在潜在的因果关系，这表明在临床实践中，睡眠特征应得到高度重视。不仅是已证实的睡眠呼吸暂停综合征，而且包括睡眠时间和睡眠状态（如失眠）都值得临床关注。我们的研究证明，睡眠特征与 NAFLD 之间的因果关系是睡眠特征变化的原因，而非 NAFLD 的发生是睡眠特征变化的原因，因果关系是单向的。
