Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Sleep Med. 2024 Aug;120:34-43. doi: 10.1016/j.sleep.2024.06.007. Epub 2024 Jun 8.
Epidemiological studies have shown that sleep disorders are risk factors for Alzheimer's disease (AD), but the causal relationship between sleep disorders and AD risk is unknown. We aim to assess the potential genetic causal association between sleep characteristics and AD, which may contribute to early identification and prediction of risk factors for AD.
Seven sleep-related traits and the outcome phenotype AD were selected from published genome-wide association studies (GWASs). These sleep-related characteristics and instrumental variables (IVs) for AD were extracted. Two-sample and multivariate Mendelian randomization (MR) analyses were performed to assess the causal relationships between sleep characteristics and AD. The inverse variance weighted (IVW), weighted median (WME), weighted mode (WM), MR-Egger regression (MR-Egger) and simple mode (SM) models were used to evaluate causality. The existence of pleiotropy was detected and corrected by MR-Egger regression, MR pleiotropy residuals and outliers.
A two-sample MR study revealed a positive causal association between sleep duration and the onset of AD (OR = 1.002, 95 % CI: 1.000-1.004), and the risk of AD increased with increasing sleep duration. The MR-Egger regression method and MR-PRESSO were used to identify and correct pleiotropy, indicating that there was no horizontal pleiotropy. Heterogeneity was evaluated by Cochran's Q, which indicated no heterogeneity. In a multivariate MR study with seven sleep characteristics corrected for each other, we found that sleep duration remained causally associated with AD (OR = 1.004, 95 % CI: 1.000-1.007). Moreover, we found that after mutual correction, daytime napping had a causal relationship with the onset of AD, and daytime napping may reduce the risk of AD (OR = 0.995, 95 % CI: 0.991-1.000).
This study is helpful for the early identification and prediction of risk factors for AD, long sleep durations are a risk factor for AD, and daytime napping can reduce the risk of AD.
流行病学研究表明，睡眠障碍是阿尔茨海默病（AD）的危险因素，但睡眠障碍与 AD 风险之间的因果关系尚不清楚。我们旨在评估睡眠特征与 AD 之间潜在的遗传因果关联，这可能有助于 AD 危险因素的早期识别和预测。
从已发表的全基因组关联研究（GWAS）中选择了 7 项与睡眠相关的特征和 AD 的结局表型。提取了这些与睡眠相关的特征和 AD 的工具变量（IVs）。采用两样本和多变量孟德尔随机化（MR）分析来评估睡眠特征与 AD 之间的因果关系。采用逆方差加权（IVW）、加权中位数（WME）、加权模式（WM）、MR-Egger 回归（MR-Egger）和简单模式（SM）模型来评估因果关系。通过 MR-Egger 回归、MR 偏倚残差和异常值检测和校正了偏倚的存在。
两样本 MR 研究显示，睡眠时间与 AD 发病之间存在正因果关系（OR=1.002，95%CI：1.000-1.004），并且随着睡眠时间的增加，AD 的风险增加。MR-Egger 回归方法和 MR-PRESSO 用于识别和校正偏倚，表明不存在水平偏倚。通过 Cochran's Q 评估了异质性，表明没有异质性。在一项对相互校正后的 7 项睡眠特征进行的多变量 MR 研究中，我们发现睡眠时间与 AD 仍存在因果关系（OR=1.004，95%CI：1.000-1.007）。此外，我们发现，在相互校正后，白天小睡与 AD 的发病有因果关系，白天小睡可能降低 AD 的风险（OR=0.995，95%CI：0.991-1.000）。
这项研究有助于 AD 危险因素的早期识别和预测，长睡眠时间是 AD 的一个危险因素，而白天小睡可以降低 AD 的风险。
