Avera McKennan Hospital and University Health Center, Sioux Falls, SD, USA.
Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Clin Epigenetics. 2024 Nov 2;16(1):151. doi: 10.1186/s13148-024-01765-0.
Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma.
The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 individuals. Principal component analysis on the clinical asthma markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates.
221 unique CpGs reached genome-wide significance at timepoint 1 after Bonferroni correction. PC7, which correlated with loadings of eosinophil counts and immunoglobulin levels, accounted for the majority of associations (204). Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points yielded a correlation of 0.81.
We identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to a robust DNA methylation profile as a new, stable biomarker for asthma.
哮喘是一种复杂的呼吸系统疾病，其肺部、血液和其他组织会出现炎症症状。我们研究了 DNA 甲基化与 35 种哮喘临床标志物之间的关系。
使用 Illumina Infinium EPIC v1 甲基化阵列评估了来自 94 个家庭的 319 名参与者的全血中的 742,442 个 CpG。他们是荷兰双胞胎登记处的一部分，其中至少有一名成员患有严重哮喘。182 名个体在 10 年后再次采集血样。对哮喘的 35 个临床标志物进行主成分分析，得出了十个主成分（PC），它们解释了总方差的 92.8%。我们对每个主成分进行了全基因组关联研究（EWAS），并对家族结构和其他协变量进行了校正。
在经过 Bonferroni 校正后，在第 1 时间点有 221 个独特的 CpG 达到了全基因组显著水平。与嗜酸性粒细胞计数和免疫球蛋白水平负荷相关的 PC7 占大多数关联（204 个）。通过 EWAS 图谱进行的富集分析确定了这 221 个 CpG 中有 190 个在哮喘和哮喘相关特征的 EWAS 中被先前鉴定过。与先前鉴定的与哮喘相关的 SNPs 进行临近评估，在两个 221 个 CpG 中的两个 CpG 附近确定了 17 个独特的 SNPs。在 182 名具有第二次时间点的表观遗传数据的个体中进行 EWAS 鉴定出了 49 个显著的 CpG。EWAS 图谱富集分析表明，在 49 个中，有 4 个与哮喘或哮喘相关特征有关。比较两个时间点确定的所有显著关联的估计值，相关性为 0.81。
我们鉴定了 270 个独特的 CpG，它们与哮喘的 35 种临床标志物生成的 PC 评分相关，无论是在横断面还是 10 年后。在两个时间点的效应大小之间存在很强的相关性。大多数关联是针对 PC7 确定的，该 PC 反映了血液嗜酸性粒细胞计数和免疫球蛋白水平，其中许多 CpG 在哮喘和哮喘相关特征的早期研究中已经有了关联。结果表明，作为一种新的、稳定的哮喘生物标志物，DNA 甲基化谱具有强大的作用。
