Skarke Carsten, Brooks Thomas, Lahens Nicholas, Grant Gregory, Sheline Yvette, FitzGerald Garret
University of Pennsylvania.
Institute of Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania; Department of Genetics, University of Pennsylvania Perelman School of Medicine.
Res Sq. 2023 Feb 15:rs.3.rs-2535978. doi: 10.21203/rs.3.rs-2535978/v1.
Many chronic disease symptomatologies involve desynchronized sleep-wake cycles, indicative of disrupted biorhythms. This can be interrogated using body temperature rhythms, which are well-established biomarkers for circadian clock function. Here, we investigated the association of wrist temperature amplitudes with a future onset of disease in the UK Biobank one year after actigraphy. Among 425 disease conditions (range 200-6,728) compared to controls (range 62,107 - 91,134), a total of 73 (36.5%) disease phenotypes were significantly associated with decreased amplitudes of wrist temperature (Benjamini-Hochberg FDR q < 0.05) and 26 (13%) PheCODEs passed a more stringent significance level (Bonferroni-correction α < 0.05). Here, for example, a two-standard deviation (1.8° Celsius) lower wrist temperature amplitude corresponded to hazard ratios of 1.91 (1.58-2.31 95% CI) for NAFLD, 1.69 (1.53-1.88) for type 2 diabetes, 1.25 (1.14-1.37) for renal failure, 1.23 (1.17-1.3) for hypertension, and 1.22 (1.11-1.33) for pneumonia. A comprehensive phenome-wide atlas of the identified mappings has been made available at http://bioinf.itmat.upenn.edu/biorhythm_atlas/. These findings strongly suggest peripheral thermoregulation as a digital biomarker.
许多慢性疾病症状涉及睡眠-觉醒周期不同步，这表明生物节律被打乱。这可以通过体温节律来研究，体温节律是昼夜节律功能公认的生物标志物。在此，我们在英国生物银行中，利用活动记录仪记录一年后，研究了手腕温度振幅与未来疾病发病之间的关联。在425种疾病情况（范围为200 - 6,728）与对照组（范围为62,107 - 91,134）进行比较时，共有73种（36.5%）疾病表型与手腕温度振幅降低显著相关（Benjamini-Hochberg错误发现率q < 0.05），26种（13%）疾病编码通过了更严格的显著性水平（Bonferroni校正α < 0.05）。例如，在此处，手腕温度振幅降低两个标准差（1.8摄氏度）对应非酒精性脂肪性肝病的风险比为1.91（95%置信区间为1.58 - 2.31），2型糖尿病为1.69（1.53 - 1.88），肾衰竭为1.25（1.14 - 1.37），高血压为1.23（1.17 - 1.3），肺炎为1.22（1.11 - 1.33）。已在http://bioinf.itmat.upenn.edu/biorhythm_atlas/上提供了已识别映射的全面全表型图谱。这些发现有力地表明外周体温调节可作为一种数字生物标志物。
