Dataset Information

Integrative analysis identifies the association between CASZ1 methylation and ischemic stroke.

ABSTRACT: Objective:To highlight potential epigenetic risk factors for blood pressure (BP) and ischemic stroke (IS) in loci identified by genome-wide association studies (GWASs). Methods:We detected DNA methylation for BP (317,756 individuals from UK Biobank) and IS (521,612 individuals from MEGASTROKE) in Europeans by using the summary data-based mendelian randomization (SMR) method. We selected the most relevant gene to validate the association in 1,207 patients with hypertensive IS and 1,269 controls from the Chinese populations. Results:We first identified 173 CpG sites in 90 genes, 337 CpG sites in 142 genes, and 9 CpG sites in 7 genes that were significantly associated with systolic, diastolic BP, and IS, respectively. The methylation level of cg12760995 in CASZ1 was associated with systolic (P SMR = 1.74 × 10-12), diastolic BP (P SMR = 2.48 × 10-10), and IS (odds ratio [OR] = 0.92 [95% confidence interval [CI]: 0.91-0.94]; P SMR = 2.28 × 10-8) in Europeans. The methylation levels of 17 sites in the promoter of CASZ1 were measured in the Chinese individuals, and 10 of them were significantly associated with IS. The higher methylation level of CASZ1 was associated with a lower risk of IS (adjusted OR = 0.97 [95% CI: 0.96-0.99]). CASZ1 seemed to be hypomethylated in hypertensive cases, and the level was negatively correlated with BP. Systolic and diastolic BP mediated approximately 61.2% (p = 3.49 × 10-6) and 45.0% (p = 0.0029) of the association between CASZ1 methylation and IS, respectively. Conclusions:This study identified DNA methylations that were associated with BP and IS. CASZ1 was hypomethylated in Chinese patients with hypertensive IS.

SUBMITTER: Mo XB

PROVIDER: S-EPMC7577558 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Integrative analysis identifies the association between <i>CASZ1</i> methylation and ischemic stroke.

Mo Xing-Bo XB Zhang Huan H Wang Ai-Li AL Xu Tan T Zhang Yong-Hong YH

Neurology. Genetics 20200901 5

<h4>Objective</h4>To highlight potential epigenetic risk factors for blood pressure (BP) and ischemic stroke (IS) in loci identified by genome-wide association studies (GWASs).<h4>Methods</h4>We detected DNA methylation for BP (317,756 individuals from UK Biobank) and IS (521,612 individuals from MEGASTROKE) in Europeans by using the summary data-based mendelian randomization (SMR) method. We selected the most relevant gene to validate the association in 1,207 patients with hypertensive IS and 1 ...[more]

PMID: 33134510

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Project description:Aim Alzheimer’s disease (AD) and ischemic stroke (IS), two major neurological diseases, are suggested to be associated in clinical and pathophysiological levels. Previous studies have provided some insights into the possible genetic mechanisms behind the correlation between AD and IS, but this issue is still not clear. We implemented transcriptomic analysis to detect common hub genes and pathways to help promote the understanding of this issue. Materials and methods Four gene expression profiling datasets (GSE16561, GSE58294, GSE63060, and GSE63061) of peripheral whole blood, which contain 108 IS samples, 284 AD samples, and 285 matched controls, were employed to detect differentially expressed genes (DEGs) for AD and IS, which were further analyzed for shared biological pathways, candidate drugs, and transcription factors. Protein-protein interaction (PPI) network and drug-target interaction analysis were applied to identify hub genes and drug targets, respectively. Result verification was done with other independent datasets (GSE37587, GSE46480, and GSE140829). The difference in proportions of various immune cells in the peripheral blood of AD and IS patients were evaluated using CIBERSORT. Results We identified 74 DEGs and 18 biological processes with statistical significance shared by AD and IS, 9 of which were immune-related pathways. Five hub genes scored high in the topological analysis of the PPI network, and we also found eight drug target genes and candidate drugs which were associated with AD and IS. As for immunological changes, an increase in the proportion of M0 macrophages was found in the peripheral circulation of both AD and IS patients, and SOD1 expression was significantly correlated with this change. Conclusion Collectively, the common DEGs and shared pathways found in this study suggest a potential shared etiology between AD and IS, behind which immune system, particularly the M0 macrophage elevation, might have important roles. While, the shared hub genes, potential therapeutic gene targets and drugs reported in this study provide promising treatment strategies for AD and IS.

Project description:Although stroke centers are widely accepted and supported, little is known about their effect on patient outcomes.To examine the association between admission to stroke centers for acute ischemic stroke and mortality.Observational study using data from the New York Statewide Planning and Research Cooperative System. We compared mortality for patients admitted with acute ischemic stroke (n = 30,947) between 2005 and 2006 at designated stroke centers and nondesignated hospitals using differential distance to hospitals as an instrumental variable to adjust for potential prehospital selection bias. Patients were followed up for mortality for 1 year after the index hospitalization through 2007. To assess whether our findings were specific to stroke, we also compared mortality for patients admitted with gastrointestinal hemorrhage (n = 39,409) or acute myocardial infarction (n = 40,024) at designated stroke centers and nondesignated hospitals.Thirty-day all-cause mortality.Among 30,947 patients with acute ischemic stroke, 15,297 (49.4%) were admitted to designated stroke centers. Using the instrumental variable analysis, admission to designated stroke centers was associated with lower 30-day all-cause mortality (10.1% vs 12.5%; adjusted mortality difference, -2.5%; 95% confidence interval [CI], -3.6% to -1.4%; P < .001) and greater use of thrombolytic therapy (4.8% vs 1.7%; adjusted difference, 2.2%; 95% CI, 1.6% to 2.8%; P < .001). Differences in mortality also were observed at 1-day, 7-day, and 1-year follow-up. The outcome differences were specific for stroke, as stroke centers and nondesignated hospitals had similar 30-day all-cause mortality rates among those with gastrointestinal hemorrhage (5.0% vs 5.8%; adjusted mortality difference, +0.3%; 95% CI, -0.5% to 1.0%; P = .50) or acute myocardial infarction (10.5% vs 12.7%; adjusted mortality difference, +0.1%; 95% CI, -0.9% to 1.1%; P = .83).Among patients with acute ischemic stroke, admission to a designated stroke center was associated with modestly lower mortality and more frequent use of thrombolytic therapy.

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Integrative analysis identifies the association between CASZ1 methylation and ischemic stroke.

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Integrative analysis identifies the association between <i>CASZ1</i> methylation and ischemic stroke.

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