Evidence map›Paper›PMID 34252155›Full record

Trial reportPloS one2021

DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.

Nicole M Davis Armstrong, Wei-Min Chen, Fang-Chi Hsu, Michael S Brewer, Natalia Cullell, Israel Fernández-Cadenas, Stephen R Williams, Michèle M Sale, Bradford B Worrall, Keith L Keene

Open access · goldAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Epigenetics as a target to mitigate excess stroke risk in people of African ancestry: A scoping review.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2024
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Nicole M Davis ArmstrongDepartment of Biology, East Carolina University, Greenville, NC, United States of America.
Wei-Min ChenCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, United States of America.
Fang-Chi HsuDepartment of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
Michael S BrewerDepartment of Biology, East Carolina University, Greenville, NC, United States of America.
Natalia CullellStroke Pharmacogenomics and Genetics, Fundació Docència i Recerca Mútua Terrassa, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, Spain.
Israel Fernández-CadenasStroke Pharmacogenomics and Genetics, Fundació Docència i Recerca Mútua Terrassa, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, Spain.
Stephen R WilliamsDepartment of Neurology, University of Virginia, Charlottesville, VA, United States of America.
Michèle M SaleCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, United States of America.
Bradford B WorrallDepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, United States of America.
Keith L KeeneDepartment of Biology, East Carolina University, Greenville, NC, United States of America.
University of Virginia · USEast Carolina University · USMútua Terrassa · ESWake Forest University · US

Funding

Vitamin Intervention for Stroke Prevention (VISP)R01NS034447 · NINDS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI TOOLE, JAMES F · 1996 to 2006
$18.0M
Pharmacogenomic studies in VISP: results & implications for clinical trial designU01HG005160 · NHGRI · UNIVERSITY OF VIRGINIA · PI SALE, MICHELE M, WORRALL, BRADFORD B · 2009 to 2011
$1.9M
NHGRI NIH HHS U01 HG005160NINDS NIH HHS R01 NS034447
6 · The paper itself

Abstract

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.

Indexed as

AcyltransferasesAgedDNA MethylationEpigenomeFemaleHumansMaleMiddle AgedStrokeVitaminsAcyltransferasesVitaminsZDHHC6 protein, human

Identifiers

PMID34252155
PMCPMC8274879
OpenAlexW3180401549

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.