DNA methylation is dynamic, varies throughout the life course, and its levels are influenced by lifestyle and environmental factors, as well as by genetic variation. The leading genetic variants at stroke risk loci identified to date explain roughly 1–2% of stroke heritability. Most of these single nucleotide polymorphisms are situated within a regulatory sequence marked by DNase I hypersensitivity sites, which would indicate involvement of an epigenetic mechanism. To detect epigenetic variants associated with stroke occurrence and stroke subtypes.

A two-stage case–control epigenome-wide association study was designed. The discovery sample with 401 samples included 218 ischaemic stroke (IS) patients, assessed at Hospital del Mar (Barcelona, Spain) and 183 controls from the REGICOR cohort. In two independent samples (N = 226 and N = 166), we replicated 22 CpG sites differentially methylated in IS in 21 loci, including 2 CpGs in locus ZFHX3, which includes known genetic variants associated with stroke. The pathways associated with these loci are inflammation and angiogenesis. The meta-analysis identified 384 differentially methylated CpGs, including loci of known stroke and vascular risk genetic variants, enriched by loci involved in lipid metabolism, adipogenesis, circadian clock, and glycolysis pathways.

We identified a set of 22 CpGs in 21 loci associated with IS. Our analysis suggests that DNA methylation changes may contribute to orchestrating gene expression that contributes to IS.

DNA甲基化是动态的，在整个生命过程中都在变化，其水平受生活方式和环境因素以及遗传变异的影响。迄今为止确定的中风风险基因座的主要遗传变异大约可解释中风遗传力的1-2％。大多数这些单核苷酸多态性位于由DNase I超敏位点标记的调控序列内，这表明参与了表观遗传机制。检测与中风发生和中风亚型相关的表观遗传变异。

设计了一个两阶段的病例对照表观基因组范围的关联研究。由401个样本组成的发现样本包括218例缺血性卒中（IS）患者，在德尔马医院（西班牙巴塞罗那）进行了评估，来自REGICOR队列的183个对照组。在两个独立的样本（N = 226和N = 166）中，我们在21个基因座中的IS中复制了22个甲基化的CpG位点，其中包括基因座ZFHX3中的2个CpG ，其中包括与中风相关的已知遗传变异。与这些基因座相关的途径是炎症和血管生成。荟萃分析确定了384种甲基化差异化CpG，包括已知中风和血管风险遗传变异的基因座，并被参与脂质代谢，脂肪形成，昼夜节律和糖酵解途径的基因座所丰富。

我们在与IS相关的21个基因座中鉴定出22个CpG。我们的分析表明，DNA甲基化的变化可能有助于编排有助于IS的基因表达。