Faquih Tariq, Potts Kaitlin, Yu Bing, Kaplan Robert, Isasi Carmen R, Qi Qibin, Taylor Kent D, Liu Peter Y, Tracy Russell P, Johnson Craig, Rich Stephen S, Clish Clary B, Gerzsten Robert E, Rotter Jerome I, Redline Susan, Sofer Tamar, Wang Heming
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
Broad Institute, Cambridge, MA, USA.
medRxiv. 2024 Sep 13:2024.09.12.24313561. doi: 10.1101/2024.09.12.24313561.
Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep, and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large scale single- and pathway-level metabolomics analyses.
Metabolomics data were available for 877 metabolites in 6,071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each metabolite on continuous ESS, adjusting for demographic, lifestyle, and physiological confounders, and in sex specific groups. Subsequently, gaussian graphical modelling was performed coupled with pathway and enrichment analyses to generate a holistic interactive network of the metabolomic profile of EDS associations.
We identified seven metabolites belonging to steroids, sphingomyelin, and long chain fatty acids sub-pathways in the primary model associated with EDS, and an additional three metabolites in the male-specific analysis. The identified metabolites particularly played a role in steroid hormone biosynthesis.
Our findings indicate that an EDS metabolomic profile is characterized by endogenous and dietary metabolites within the steroid hormone biosynthesis pathway, with some pathways that differ by sex. Our findings identify potential pathways to target for addressing the causes or consequences of EDS and related sleep disorders.
Details regarding funding supporting this work and all studies involved are provided in the acknowledgments section.
日间过度嗜睡（EDS）是一个复杂的睡眠问题，影响着约33%的美国人口。尽管EDS通常与睡眠不足以及其他睡眠和昼夜节律紊乱同时出现，但最近的研究已经揭示了EDS背后独特的遗传标记和代谢途径。在此，我们旨在通过大规模的单代谢物水平和通路水平代谢组学分析，进一步阐明EDS的生物学特征。
西班牙裔社区健康研究/拉丁裔研究（HCHS/SOL）中6071名个体的877种代谢物的代谢组学数据可用，并且使用爱泼华嗜睡量表（ESS）问卷对EDS进行评估。我们对每种代谢物与连续的ESS进行线性回归，调整人口统计学、生活方式和生理混杂因素，并在特定性别的组中进行分析。随后，进行高斯图形建模，并结合通路和富集分析，以生成EDS关联代谢组学特征的整体交互网络。
在与EDS相关的主要模型中，我们鉴定出七种属于类固醇、鞘磷脂和长链脂肪酸子通路的代谢物，在男性特异性分析中又鉴定出另外三种代谢物。所鉴定的代谢物在类固醇激素生物合成中特别发挥作用。
我们的研究结果表明，EDS的代谢组学特征是类固醇激素生物合成途径中的内源性和饮食代谢物，并且某些途径存在性别差异。我们的研究结果确定了针对EDS及相关睡眠障碍的原因或后果的潜在靶向途径。
致谢部分提供了支持这项工作及所有相关研究的资助详情。
