Background

Latinos are heavily affected with childhood asthma. Little is known about epigenetic mechanisms of asthma in Latino youth.

Methods

We conducted a meta-analysis of two epigenome-wide association studies (EWAS) of asthma, using DNA from white blood cells (WBCs) from 1,136 Latino children and youth aged 6 to 20 years. Genes near the top CpG sites in this EWAS were examined in a pathway enrichment analysis, and we then assessed whether our results replicated those from publicly available data from three independent EWAS conducted in non-Latino populations.

Results

DNA methylation profiles differed between subjects with and without asthma. After adjustment for covariates and multiple testing, two CpGs were differentially methylated at a false discovery rate (FDR)-adjusted P < 0.1, and 193 CpG sites were differentially methylated at FDR-adjusted P < 0.2. The two top CpGs are near genes relevant to inflammatory signaling, including CAMK1D (Calcium/Calmodulin Dependent Protein Kinase ID) and TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains). Moreover, 25 genomic regions were differentially methylated between subjects with and without asthma, at Šidák-corrected P < 0.10. An enrichment analysis then identified the TGF-beta pathway as most relevant to asthma in our analysis, and we replicated some of the top signals from publicly available EWAS datasets in non-Hispanic populations.

Conclusions

We have identified novel epigenetic markers of asthma in WBCs from Latino children and youth, while also replicating previous results from studies conducted in non-Latinos.

中文翻译：

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拉丁美洲儿童和青少年白细胞和哮喘中DNA甲基化的全基因组研究

背景

拉丁裔深受儿童哮喘病的影响。关于拉丁美洲青年哮喘的表观遗传机制知之甚少。

方法

我们使用来自1136名拉丁裔儿童和6至20岁青年的白细胞（WBC）的DNA，对两项哮喘的表观基因组关联研究（EWAS）进行了荟萃分析。在路径富集分析中检查了该EWAS顶部CpG位点附近的基因，然后我们评估了我们的结果是否重复了来自非拉丁裔人群进行的三个独立EWAS的可公开获得的数据。

结果

在患有和不患有哮喘的受试者之间，DNA甲基化特征不同。调整协变量并进行多次测试后，以错误发现率（FDR）调整的P <0.1对两个CpG进行了甲基化，以FDR调整的P <0.2进行了193个CpG位置进行了甲基化。前两个CpG接近与炎症信号相关的基因，包括CAMK1D（钙/钙调蛋白依赖性蛋白激酶ID）和TIGIT（具有Ig和ITIM域的T细胞免疫受体）。而且，有和没有哮喘的受试者之间有25个基因组区域甲基化差异，以Šidák校正后的P <0.10。在我们的分析中，一项富集分析随后确定了TGF-β途径与哮喘最相关，我们从非西班牙裔人群中复制了可公开获得的EWAS数据集中的一些重要信号。

结论

我们从拉丁裔儿童和青少年中发现了WBC中哮喘的新表观遗传学标记，同时也复制了在非拉丁裔中进行的研究的先前结果。