Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Epidemiology, Harvard T.H.Chan School of Public Health, Boston, MA, USA.
Nat Commun. 2023 Sep 7;14(1):5495. doi: 10.1038/s41467-023-41300-y.
Bronchiolitis is the most common lower respiratory infection in infants, yet its pathobiology remains unclear. Here we present blood DNA methylation data from 625 infants hospitalized with bronchiolitis in a 17-center prospective study, and associate them with disease severity. We investigate differentially methylated CpGs (DMCs) for disease severity. We characterize the DMCs based on their association with cell and tissues types, biological pathways, and gene expression. Lastly, we also examine the relationships of severity-related DMCs with respiratory and immune traits in independent cohorts. We identify 33 DMCs associated with severity. These DMCs are differentially methylated in blood immune cells. These DMCs are also significantly enriched in multiple tissues (e.g., lung) and cells (e.g., small airway epithelial cells), and biological pathways (e.g., interleukin-1-mediated signaling). Additionally, these DMCs are associated with respiratory and immune traits (e.g., asthma, lung function, IgE levels). Our study suggests the role of DNA methylation in bronchiolitis severity.
毛细支气管炎是婴儿最常见的下呼吸道感染，但它的发病机制仍不清楚。在这里，我们从 625 名在 17 个中心进行的前瞻性研究中因毛细支气管炎住院的婴儿中提供了血液 DNA 甲基化数据，并将其与疾病严重程度相关联。我们研究了与疾病严重程度相关的差异甲基化 CpG（DMC）。我们根据 DMC 与细胞和组织类型、生物途径和基因表达的关联来对其进行特征描述。最后，我们还在独立队列中检查了与严重程度相关的 DMC 与呼吸和免疫特征之间的关系。我们确定了 33 个与严重程度相关的 DMC。这些 DMC 在血液免疫细胞中表现出甲基化差异。这些 DMC 在多个组织（如肺）和细胞（如小气道上皮细胞）以及生物途径（如白细胞介素 1 介导的信号通路）中也显著富集。此外，这些 DMC 与呼吸和免疫特征（如哮喘、肺功能、IgE 水平）相关。我们的研究表明 DNA 甲基化在毛细支气管炎严重程度中的作用。
