Bian Keyu, Zhang Pan, Xu Gelin, Sun Wen
Department of Neurology, Wujin TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou, Jiangsu, China; Department of Neurology, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; Department of Neurology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.
Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
J Affect Disord. 2025 Feb 15;371:261-267. doi: 10.1016/j.jad.2024.11.040. Epub 2024 Nov 26.
Cardiometabolic diseases (CMD) are major global health concerns with significant morbidity and mortality. Fatigue, a common but often overlooked symptom, has been postulated as both a potential risk factor for and a consequence of these conditions. However, the relationships between fatigue and CMD remain unclear. This study aimed to investigate the relationship between fatigue and CMD using observational and genetic approaches.
Observational study was conducted in the UK biobank. Genetic method was employed a bidirectional MR approach to examine the causal relationship between fatigue and CMD. Genetic variants associated with fatigue were identified through a GWAS, and summary statistics from the largest available GWAS were used to obtain variants associated with stroke, CAD, T2D, and HF. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Multivariable MR and mediation analysis were also employed.
Observational analyses indicated that individuals with fatigue had a significantly increased risk of developing stroke (HR 1.44, 95 % CI 1.27-1.63), T2D (HR 1.46, 95 % CI 1.41-1.51), CAD (HR 1.45, 95 % CI 1.4-1.5), and HF (HR 1.60, 95 % CI 1.52-1.68). Mendelian randomization analyses further supported a causal relationship. Additionally, observational and genetic analyses showed T2D was found to be associated with increased levels of fatigue. Mediation analysis identified lipid metabolites as mediators in the relationship between fatigue and CMD.
This study highlights a bidirectional relationship between fatigue and CMD, underscoring the importance of considering fatigue in the context of cardiometabolic health.
Not applicable.
心脏代谢疾病（CMD）是全球主要的健康问题，具有较高的发病率和死亡率。疲劳是一种常见但常被忽视的症状，被认为既是这些疾病的潜在风险因素，也是其结果。然而，疲劳与CMD之间的关系仍不明确。本研究旨在通过观察性和遗传学方法探讨疲劳与CMD之间的关系。
在英国生物银行进行观察性研究。采用遗传方法，运用双向孟德尔随机化方法来检验疲劳与CMD之间的因果关系。通过全基因组关联研究（GWAS）确定与疲劳相关的基因变异，并使用现有最大GWAS的汇总统计数据来获取与中风、冠心病（CAD）、2型糖尿病（T2D）和心力衰竭（HF）相关的变异。进行逆方差加权（IVW）分析，并采用加权中位数、孟德尔随机化Egger回归和MR-PRESSO方法进行敏感性分析。还采用了多变量孟德尔随机化分析和中介分析。
观察性分析表明，疲劳个体发生中风（风险比[HR] 1.44，95%置信区间[CI] 1.27 - 1.63）、T2D（HR 1.46，95% CI 1.41 - 1.51）、CAD（HR 1.45，95% CI 1.4 - 1.5）和HF（HR 1.60，95% CI 1.52 - 1.68）的风险显著增加。孟德尔随机化分析进一步支持了因果关系。此外，观察性和遗传学分析表明，T2D与疲劳水平升高有关。中介分析确定脂质代谢物是疲劳与CMD关系中的中介因素。
本研究强调了疲劳与CMD之间的双向关系，突出了在心脏代谢健康背景下考虑疲劳的重要性。
不适用。
