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

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-...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cce8071ac4734336850320c53dea1cbf
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cce8071ac4734336850320c53dea1cbf
record_format	dspace
spelling	oai:doaj.org-article:cce8071ac4734336850320c53dea1cbf2021-12-02T20:15:27ZDNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.1932-620310.1371/journal.pone.0254562https://doaj.org/article/cce8071ac4734336850320c53dea1cbf2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254562https://doaj.org/toc/1932-6203Aberrant 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.Nicole M Davis ArmstrongWei-Min ChenFang-Chi HsuMichael S BrewerNatalia CullellIsrael Fernández-CadenasStephen R WilliamsMichèle M SaleBradford B WorrallKeith L KeenePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254562 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
description	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.
format	article
author	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
author_facet	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
author_sort	Nicole M Davis Armstrong
title	DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
title_short	DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
title_full	DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
title_fullStr	DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
title_full_unstemmed	DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial.
title_sort	dna methylation analyses identify an intronic zdhhc6 locus associated with time to recurrent stroke in the vitamin intervention for stroke prevention (visp) clinical trial.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/cce8071ac4734336850320c53dea1cbf
work_keys_str_mv	AT nicolemdavisarmstrong dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT weiminchen dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT fangchihsu dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT michaelsbrewer dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT nataliacullell dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT israelfernandezcadenas dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT stephenrwilliams dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT michelemsale dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT bradfordbworrall dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial AT keithlkeene dnamethylationanalysesidentifyanintroniczdhhc6locusassociatedwithtimetorecurrentstrokeinthevitamininterventionforstrokepreventionvispclinicaltrial
_version_	1718374610548817920

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

Ejemplares similares