Peng, HaoPalma Gudiel, HelenaSoriano Tarraga, CarolinaJimenez-Conde, JordiZhang, MingzhiZhang, YonghongZhao, Jinying2024-02-292024-02-292023Peng H, Palma-Gudiel H, Soriano-Tarraga C, Jimenez-Conde J, Zhang M, Zhang Y, Zhao J. Epigenome-wide association study identifies novel genes associated with ischemic stroke. Clin Epigenetics. 2023 Jun 27;15(1):106. DOI: 10.1186/s13148-023-01520-x1868-7075http://hdl.handle.net/10230/59289Background: 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13148-023-01520-xCRISPR/dCas9-Dnmt3aChinese populationDNA methylationEWASIschemic strokeinfo:eu-repo/semantics/openAccess