Liu Patrick Z, Raizen David M, Skarke Carsten, Brooks Thomas G, Anafi Ron C
Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sleep. 2025 Feb 10;48(2). doi: 10.1093/sleep/zsae243.
The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is based on a constellation of symptoms which center around fatigue. However, fatigue is commonly reported in the general population by people without CFS. Does the biology underlying fatigue in patients with CFS also drive fatigue experienced by individuals without CFS?
We used UK Biobank actigraphy data to characterize differences in physical activity patterns and daily temperature rhythms between participants diagnosed with CFS compared to controls. We then tested if single nucleotide variants (SNVs) previously associated with CFS are also associated with the variation of these actigraphic CFS correlates and/or subjective fatigue symptoms in the general population.
Participants diagnosed with CFS (n = 295) had significantly decreased overall movement (Cohen's d = 0.220, 95% CI of -0.335 to -0.106, p-value = 2.42 × 10-15), lower activity amplitudes (Cohen's d = -0.377, 95% CI of -0.492 to -0.262, p-value = 1.74 × 10-6), and lower wrist temperature amplitudes (Cohen's d = -0.173, 95% CI of -0.288 to -0.059, p-value = .002) compared to controls (n = 63,133). Of 30 tested SNVs associated in the literature with CFS, one was associated in the control population with subjective fatigue and one with actigraphic measurements (FDR < 0.05).
The genetic overlap of CFS risk with actigraphy and subjective fatigue phenotypes suggests that some biological mechanisms underlying pathologic fatigue in patients with CFS also underlie fatigue symptoms at a broader population level. Therefore, understanding the biology of fatigue in general may inform our understanding of CFS pathophysiology.
肌痛性脑脊髓炎/慢性疲劳综合征（CFS）的诊断基于一系列以疲劳为核心的症状。然而，普通人群中没有CFS的人也普遍报告有疲劳症状。CFS患者疲劳背后的生物学机制是否也会导致没有CFS的个体出现疲劳？
我们使用英国生物银行的活动记录仪数据来描述被诊断为CFS的参与者与对照组在身体活动模式和每日体温节律上的差异。然后我们测试了先前与CFS相关的单核苷酸变异（SNV）是否也与这些活动记录仪记录的CFS相关指标的变化和/或普通人群中的主观疲劳症状相关。
与对照组（n = 63133）相比，被诊断为CFS的参与者（n = 295）总体活动显著减少（Cohen's d = 0.220，95%置信区间为-0.335至-0.106，p值 = 2.42×10-15），活动幅度较低（Cohen's d = -0.377，95%置信区间为-0.492至-0.262，p值 = 1.74×10-6），手腕温度幅度较低（Cohen's d = -0.173，95%置信区间为-0.288至-0.059，p值 = 0.002）。在文献中与CFS相关的30个测试SNV中，一个在对照组人群中与主观疲劳相关，一个与活动记录仪测量结果相关（错误发现率<0.05）。
CFS风险与活动记录仪记录和主观疲劳表型的遗传重叠表明，CFS患者病理性疲劳背后的一些生物学机制在更广泛的人群水平上也是疲劳症状的基础。因此，总体上了解疲劳的生物学机制可能有助于我们理解CFS的病理生理学。
