Zhao Sheng, Jiang Huijie, Liang Zong-Hui, Ju Hong
Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Radiology, Jian'an District Centre Hospital of Fudan University, Shanghai, China.
Front Genet. 2020 Jan 24;10:1336. doi: 10.3389/fgene.2019.01336. eCollection 2019.
Stroke ranks the second leading cause of death among people over the age of 60 in the world. Stroke is widely regarded as a complex disease that is affected by genetic and environmental factors. Evidence from twin and family studies suggests that genetic factors may play an important role in its pathogenesis. Therefore, research on the genetic association of susceptibility genes can help understand the mechanism of stroke. Genome-wide association study (GWAS) has found a large number of stroke-related loci, but their mechanism is unknown. In order to explore the function of single-nucleotide polymorphisms (SNPs) at the molecular level, in this paper, we integrated 8 GWAS datasets with brain expression quantitative trait loci (eQTL) dataset to identify SNPs and genes which are related to four types of stroke (ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke). Thirty-eight SNPs which can affect 14 genes expression are found to be associated with stroke. Among these 14 genes, 10 genes expression are associated with ischemic stroke, one gene for large artery stroke, six genes for cardioembolic stroke and eight genes for small vessel stroke. To explore the effects of environmental factors on stroke, we identified methylation susceptibility loci associated with stroke using methylation quantitative trait loci (MQTL). Thirty-one of these 38 SNPs are at greater risk of methylation and can significantly change gene expression level. Overall, the genetic pathogenesis of stroke is explored from locus to gene, gene to gene expression and gene expression to phenotype.
中风是全球60岁以上人群中第二大死因。中风被广泛认为是一种受遗传和环境因素影响的复杂疾病。双胞胎和家族研究的证据表明，遗传因素可能在其发病机制中起重要作用。因此，对易感基因的遗传关联研究有助于了解中风的发病机制。全基因组关联研究（GWAS）已经发现了大量与中风相关的基因座，但其机制尚不清楚。为了在分子水平上探索单核苷酸多态性（SNP）的功能，在本文中，我们将8个GWAS数据集与脑表达定量性状基因座（eQTL）数据集整合，以识别与四种类型的中风（缺血性中风、大动脉中风、心源性栓塞性中风、小血管中风）相关的SNP和基因。发现38个影响14个基因表达的SNP与中风相关。在这14个基因中，10个基因的表达与缺血性中风相关，1个基因与大动脉中风相关，6个基因与心源性栓塞性中风相关，8个基因与小血管中风相关。为了探索环境因素对中风的影响，我们使用甲基化定量性状基因座（MQTL）鉴定了与中风相关的甲基化易感基因座。这38个SNP中有31个甲基化风险更高，可显著改变基因表达水平。总体而言，从中风的基因座到基因、从基因到基因表达、从基因表达再到表型，探索了中风的遗传发病机制。
