DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
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DOI：
10.1371/journal.pone.0254562
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Keene KL
中科院分区：
文献类型：
--
作者：
Davis Armstrong NM;Chen WM;Hsu FC;Brewer MS;Cullell N;Fernández-Cadenas I;Williams SR;Sale MM;Worrall BB;Keene KL
异常的 DNA 甲基化谱与多种心血管疾病有关。然而，很少有研究调查这些表观遗传修饰如何导致中风复发。本研究的目的是确定与欧洲和非洲血统个体的脑和心血管事件复发时间相关的甲基化位点。使用 Illumina HumanMmethylation 450K BeadChip 微阵列生成了维生素干预预防中风临床试验中 180 名个体的 DNA 甲基化图谱，得出 470,871 个常染色体 CpG 位点的 β 值。使用Cox比例风险回归模型进行种族分层生存分析，以了解每个甲基化位点与卒中复发或复合血管事件时间之间的关联。结果在西班牙巴塞罗那的希伯伦山谷大学医院队列中得到了验证。使用加权基因共表达网络分析生成甲基化位点的网络分析。初步分析确定了与卒中复发时间相关的四个显着基因座：cg04059318、ch.2.81927627R、cg03584380 和 cg24875416。二次分析确定了与复合血管终点时间相关的三个基因座：cg00076998、cg16758041 和 cg02365967。基因座 cg03584380 位于 ZDHHC6 的内含子中，在希伯伦谷大学医院队列中进行了复制。这项研究的结果表明，cg03584380 的甲基化程度与两个不同种族群体的中风或复合血管事件的复发时间相关。此外，基因座模块与临床特征和血液生物标志物相关，包括既往中风次数、凝血酶原片段1+2、血栓调节蛋白、凝血酶-抗凝血酶复合物、甘油三酯水平和组织纤溶酶原激活剂。最终，这些基因座可以作为潜在的表观遗传生物标志物，可以识别易复发人群中的高危个体。
Aberrant DNA methylation profiles have been implicated in numerous cardiovascular diseases; however, few studies have investigated how these epigenetic modifications contribute to stroke recurrence. The aim of this study was to identify methylation loci associated with the time to recurrent cerebro- and cardiovascular events in individuals of European and African descent. DNA methylation profiles were generated for 180 individuals from the Vitamin Intervention for Stroke Prevention clinical trial using Illumina HumanMethylation 450K BeadChip microarrays, resulting in beta values for 470,871 autosomal CpG sites. Ethnicity-stratified survival analyses were performed using Cox Proportional Hazards regression models for associations between each methylation locus and the time to recurrent stroke or composite vascular event. Results were validated in the Vall d’Hebron University Hospital cohort from Barcelona, Spain. Network analyses of the methylation loci were generated using weighted gene coexpression network analysis. Primary analysis identified four significant loci, cg04059318, ch.2.81927627R, cg03584380, and cg24875416, associated with time to recurrent stroke. Secondary analysis identified three loci, cg00076998, cg16758041, and cg02365967, associated with time to composite vascular endpoint. Locus cg03584380, which is located in an intron of ZDHHC6, was replicated in the Vall d’Hebron University Hospital cohort. The results from this study implicate the degree of methylation at cg03584380 is associated with the time of recurrence for stroke or composite vascular events across two ethnically diverse groups. Furthermore, modules of loci were associated with clinical traits and blood biomarkers including previous number of strokes, prothrombin fragments 1 + 2, thrombomodulin, thrombin-antithrombin complex, triglyceride levels, and tissue plasminogen activator. Ultimately, these loci could serve as potential epigenetic biomarkers that could identify at-risk individuals in recurrence-prone populations.
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影响因子：
--
作者：
Bai B;Man AW;Yang K;Guo Y;Xu C;Tse HF;Han W;Bloksgaard M;De Mey JG;Vanhoutte PM;Xu A;Wang Y
通讯作者：
Wang Y
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
4.3
作者：
Eden E;Lipson D;Yogev S;Yakhini Z
通讯作者：
Yakhini Z