Epigenome-wide association analysis of infant bronchiolitis severity: a multicenter prospective cohort study.
Epigenome-wide association analysis of infant bronchiolitis severity: a multicenter prospective cohort study.
复制标题
DOI：
10.1038/s41467-023-41300-y
复制
发表时间：
2023-09-07
影响因子：
16.6
通讯作者：
Hasegawa K
中科院分区：
文献类型：
--
作者：
Zhu Z;Li Y;Freishtat RJ;Celedón JC;Espinola JA;Harmon B;Hahn A;Camargo CA Jr;Liang L;Hasegawa K
细支气管炎是婴儿最常见的下呼吸道感染，但其病理学仍不清楚。在此，我们展示了一项 17 中心前瞻性研究中 625 名因细支气管炎住院婴儿的血液 DNA 甲基化数据，并将其与疾病严重程度相关联。我们研究差异甲基化 CpG (DMC) 的疾病严重程度。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表征 DMC。最后，我们还研究了独立队列中与严重程度相关的 DMC 与呼吸和免疫特征的关系。我们确定了 33 个与严重程度相关的 DMC。这些 DMC 在血液免疫细胞中被差异甲基化。这些 DMC 在多种组织（例如肺）和细胞（例如小气道上皮细胞）和生物途径（例如白细胞介素 1 介导的信号传导）中也显着富集。此外，这些 DMC 与呼吸和免疫特征（例如哮喘、肺功能、IgE 水平）相关。我们的研究表明 DNA 甲基化在细支气管炎严重程度中的作用。与疾病相关的 DNA 甲基化模式可以揭示与疾病病因有关的基因。在此，作者确定了与细支气管炎严重程度相关并在组织、细胞和通路中发挥重要作用的血液 DNA 甲基化特征。
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. DNA methylation patterns that are associated with disease can reveal genes involved in disease etiology. Here, the authors identify blood DNA methylation signatures that are associated with bronchiolitis severity and play important roles in tissues, cells, and pathways.
登录
查看更多内容
影响因子：
76.2
作者：
Makrinioti, Heidi;Camargo, Carlos A.;Zhu, Zhaozhong;Freishtat, Robert J.;Hasegawa, Kohei
通讯作者：
Hasegawa, Kohei
DOI：
10.1073/pnas.2116467119
发表时间：
2022-06-14
影响因子：
11.1
作者：
通讯作者：
--
DOI：
10.1164/rccm.202108-1907oc
发表时间：
2022-08-01
影响因子：
24.7
作者：
通讯作者：
--
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
16.6
作者：
Cardenas, Andres;Sordillo, Joanne E.;Gold, Diane R.
通讯作者：
Gold, Diane R.