Epigenome-wide association study identifies novel genes associated with ischemic stroke

Background: DNA methylation has previously been associated with ischemic stroke, but the specific genes and their functional roles in ischemic stroke remain to be determined. Here we aimed to identify differentially methylated genes that play a functional role in ischemic stroke in a Chinese populat...

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Autores: Peng, Hao, Palma Gudiel, Helena, Soriano Tarraga, Carolina, Jiménez Conde, Jordi, Zhang, Mingzhi, Zhang, Yonghong, Zhao, Jinying
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/59289
Acceso en línea:http://hdl.handle.net/10230/59289
http://dx.doi.org/10.1186/s13148-023-01520-x
Access Level:acceso abierto
Palabra clave:CRISPR/dCas9-Dnmt3a
Chinese population
DNA methylation
EWAS
Ischemic stroke
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spelling Epigenome-wide association study identifies novel genes associated with ischemic strokePeng, HaoPalma Gudiel, HelenaSoriano Tarraga, CarolinaJiménez Conde, JordiZhang, MingzhiZhang, YonghongZhao, JinyingCRISPR/dCas9-Dnmt3aChinese populationDNA methylationEWASIschemic strokeBackground: DNA methylation has previously been associated with ischemic stroke, but the specific genes and their functional roles in ischemic stroke remain to be determined. Here we aimed to identify differentially methylated genes that play a functional role in ischemic stroke in a Chinese population. Results: Genome-wide DNA methylation assessed with the Illumina Methylation EPIC Array in a discovery sample including 80 Chinese adults (40 cases vs. 40 controls) found that patients with ischemic stroke were characterized by increased DNA methylation at six CpG loci (individually located at TRIM6, FLRT2, SOX1, SOX17, AGBL4, and FAM84A, respectively) and decreased DNA methylation at one additional locus (located at TLN2). Targeted bisulfite sequencing confirmed six of these differentially methylated probes in an independent Chinese population (853 cases vs. 918 controls), and one probe (located at TRIM6) was further verified in an external European cohort (207 cases vs. 83 controls). Experimental manipulation of DNA methylation in engineered human umbilical vein endothelial cells indicated that the identified differentially methylated probes located at TRIM6, TLN2, and FLRT2 genes may play a role in endothelial cell adhesion and atherosclerosis. Conclusions: Altered DNA methylation of the TRIM6, TLN2, and FLRT2 genes may play a functional role in ischemic stroke in Chinese populations.BioMed Central202420242023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/59289http://dx.doi.org/10.1186/s13148-023-01520-xreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésClin Epigenetics. 2023 Jun 27;15(1):106© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/592892026-06-12T07:21:37Z
dc.title.none.fl_str_mv Epigenome-wide association study identifies novel genes associated with ischemic stroke
title Epigenome-wide association study identifies novel genes associated with ischemic stroke
spellingShingle Epigenome-wide association study identifies novel genes associated with ischemic stroke
Peng, Hao
CRISPR/dCas9-Dnmt3a
Chinese population
DNA methylation
EWAS
Ischemic stroke
title_short Epigenome-wide association study identifies novel genes associated with ischemic stroke
title_full Epigenome-wide association study identifies novel genes associated with ischemic stroke
title_fullStr Epigenome-wide association study identifies novel genes associated with ischemic stroke
title_full_unstemmed Epigenome-wide association study identifies novel genes associated with ischemic stroke
title_sort Epigenome-wide association study identifies novel genes associated with ischemic stroke
dc.creator.none.fl_str_mv Peng, Hao
Palma Gudiel, Helena
Soriano Tarraga, Carolina
Jiménez Conde, Jordi
Zhang, Mingzhi
Zhang, Yonghong
Zhao, Jinying
author Peng, Hao
author_facet Peng, Hao
Palma Gudiel, Helena
Soriano Tarraga, Carolina
Jiménez Conde, Jordi
Zhang, Mingzhi
Zhang, Yonghong
Zhao, Jinying
author_role author
author2 Palma Gudiel, Helena
Soriano Tarraga, Carolina
Jiménez Conde, Jordi
Zhang, Mingzhi
Zhang, Yonghong
Zhao, Jinying
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CRISPR/dCas9-Dnmt3a
Chinese population
DNA methylation
EWAS
Ischemic stroke
topic CRISPR/dCas9-Dnmt3a
Chinese population
DNA methylation
EWAS
Ischemic stroke
description Background: DNA methylation has previously been associated with ischemic stroke, but the specific genes and their functional roles in ischemic stroke remain to be determined. Here we aimed to identify differentially methylated genes that play a functional role in ischemic stroke in a Chinese population. Results: Genome-wide DNA methylation assessed with the Illumina Methylation EPIC Array in a discovery sample including 80 Chinese adults (40 cases vs. 40 controls) found that patients with ischemic stroke were characterized by increased DNA methylation at six CpG loci (individually located at TRIM6, FLRT2, SOX1, SOX17, AGBL4, and FAM84A, respectively) and decreased DNA methylation at one additional locus (located at TLN2). Targeted bisulfite sequencing confirmed six of these differentially methylated probes in an independent Chinese population (853 cases vs. 918 controls), and one probe (located at TRIM6) was further verified in an external European cohort (207 cases vs. 83 controls). Experimental manipulation of DNA methylation in engineered human umbilical vein endothelial cells indicated that the identified differentially methylated probes located at TRIM6, TLN2, and FLRT2 genes may play a role in endothelial cell adhesion and atherosclerosis. Conclusions: Altered DNA methylation of the TRIM6, TLN2, and FLRT2 genes may play a functional role in ischemic stroke in Chinese populations.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/59289
http://dx.doi.org/10.1186/s13148-023-01520-x
url http://hdl.handle.net/10230/59289
http://dx.doi.org/10.1186/s13148-023-01520-x
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Clin Epigenetics. 2023 Jun 27;15(1):106
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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