Che Lu, Zang Han, Bi Yaodan, Wen Bei, Xu Li
Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People's Republic of China.
Nat Sci Sleep. 2025 Feb 7;17:271-284. doi: 10.2147/NSS.S497173. eCollection 2025.
Observational studies have demonstrated a strong association between sleep disturbances and frailty. However, the causality remains inconclusive. We aimed to investigate the bidirectional causal relationships between frailty measures and sleep disturbances employing a two-sample Mendelian randomization (MR) analysis.
Two-sample MR analyses were performed based on large-scale genome-wide association studies (GWAS) of the European population for frailty index (FI) (N = 175,226), Fried Frailty Score (FFS) (N = 386,565), insomnia (N = 283,595), sleep duration (N = 445,966) and sleep apnea (N = 523,366). We conducted the causal estimates using the inverse variance-weighted method (IVW), with sensitivity analyses using MR-Egger, weighted median, weighted mode, and MR pleiotropy residual sum and outlier (MR-PRESSO) analysis. Cochran's Q test was performed to assess heterogeneity.
We found that genetically predicted FI was associated with shorter sleep duration and sleep apnea. The genetically predicted FFS was associated with insomnia, shorter sleep duration, and sleep apnea. In the reverse direction analysis, genetic liability to insomnia, short sleep duration, and long sleep duration were associated with an increase in FI. Genetic liability to short sleep duration and long sleep duration were associated with an increase in FFS.
Our study provided genetic evidence supporting the bidirectional causality between frailty measures and sleep disturbances. The findings contribute to the prevention and management of frailty and sleep disturbances.
观察性研究表明睡眠障碍与衰弱之间存在密切关联。然而，因果关系仍不明确。我们旨在采用两样本孟德尔随机化（MR）分析来研究衰弱指标与睡眠障碍之间的双向因果关系。
基于欧洲人群的大规模全基因组关联研究（GWAS），对衰弱指数（FI）（N = 175,226）、弗里德衰弱评分（FFS）（N = 386,565）、失眠（N = 283,595）、睡眠时间（N = 445,966）和睡眠呼吸暂停（N = 523,366）进行两样本MR分析。我们使用逆方差加权法（IVW）进行因果估计，并使用MR-Egger、加权中位数、加权众数和MR多效性残差和离群值（MR-PRESSO）分析进行敏感性分析。进行 Cochr an's Q检验以评估异质性。
我们发现基因预测的FI与较短的睡眠时间和睡眠呼吸暂停有关。基因预测的FFS与失眠、较短的睡眠时间和睡眠呼吸暂停有关。在反向分析中，失眠、短睡眠时间和长睡眠时间的遗传易感性与FI增加有关。短睡眠时间和长睡眠时间的遗传易感性与FFS增加有关。
我们的研究提供了遗传证据，支持衰弱指标与睡眠障碍之间的双向因果关系。这些发现有助于衰弱和睡眠障碍的预防和管理。
