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Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification
BACKGROUND: Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression signatures of early MI and subclinical atherosclerosis in the Framingham Heart Stud...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874462/ https://www.ncbi.nlm.nih.gov/pubmed/33568140 http://dx.doi.org/10.1186/s12920-020-00838-2 |
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author | Zhang, Xiaoling van Rooij, Jeroen G. J. Wakabayashi, Yoshiyuki Hwang, Shih-Jen Yang, Yanqin Ghanbari, Mohsen Bos, Daniel Levy, Daniel Johnson, Andrew D. van Meurs, Joyce B. J. Kavousi, Maryam Zhu, Jun O’Donnell, Christopher J. |
author_facet | Zhang, Xiaoling van Rooij, Jeroen G. J. Wakabayashi, Yoshiyuki Hwang, Shih-Jen Yang, Yanqin Ghanbari, Mohsen Bos, Daniel Levy, Daniel Johnson, Andrew D. van Meurs, Joyce B. J. Kavousi, Maryam Zhu, Jun O’Donnell, Christopher J. |
author_sort | Zhang, Xiaoling |
collection | PubMed |
description | BACKGROUND: Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression signatures of early MI and subclinical atherosclerosis in the Framingham Heart Study (FHS). In this study, we conducted paired-end RNA sequencing on whole blood collected from 198 FHS participants (55 with a history of early MI, 72 with high CAC without prior MI, and 71 controls free of elevated CAC levels or history of MI). We applied DESeq2 to identify coding-genes and long intergenic noncoding RNAs (lincRNAs) differentially expressed in MI and high CAC, respectively, compared with the control. RESULTS: On average, 150 million paired-end reads were obtained for each sample. At the false discovery rate (FDR) < 0.1, we found 68 coding genes and 2 lincRNAs that were differentially expressed in early MI versus controls. Among them, 60 coding genes were detectable and thus tested in an independent RNA-Seq data of 807 individuals from the Rotterdam Study, and 8 genes were supported by p value and direction of the effect. Immune response, lipid metabolic process, and interferon regulatory factor were enriched in these 68 genes. By contrast, only 3 coding genes and 1 lincRNA were differentially expressed in high CAC versus controls. APOD, encoding a component of high-density lipoprotein, was significantly downregulated in both early MI (FDR = 0.007) and high CAC (FDR = 0.01) compared with controls. CONCLUSIONS: We identified transcriptomic signatures of early MI that include differentially expressed protein-coding genes and lincRNAs, suggesting important roles for protein-coding genes and lincRNAs in the pathogenesis of MI. |
format | Online Article Text |
id | pubmed-7874462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-78744622021-02-11 Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification Zhang, Xiaoling van Rooij, Jeroen G. J. Wakabayashi, Yoshiyuki Hwang, Shih-Jen Yang, Yanqin Ghanbari, Mohsen Bos, Daniel Levy, Daniel Johnson, Andrew D. van Meurs, Joyce B. J. Kavousi, Maryam Zhu, Jun O’Donnell, Christopher J. BMC Med Genomics Research Article BACKGROUND: Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression signatures of early MI and subclinical atherosclerosis in the Framingham Heart Study (FHS). In this study, we conducted paired-end RNA sequencing on whole blood collected from 198 FHS participants (55 with a history of early MI, 72 with high CAC without prior MI, and 71 controls free of elevated CAC levels or history of MI). We applied DESeq2 to identify coding-genes and long intergenic noncoding RNAs (lincRNAs) differentially expressed in MI and high CAC, respectively, compared with the control. RESULTS: On average, 150 million paired-end reads were obtained for each sample. At the false discovery rate (FDR) < 0.1, we found 68 coding genes and 2 lincRNAs that were differentially expressed in early MI versus controls. Among them, 60 coding genes were detectable and thus tested in an independent RNA-Seq data of 807 individuals from the Rotterdam Study, and 8 genes were supported by p value and direction of the effect. Immune response, lipid metabolic process, and interferon regulatory factor were enriched in these 68 genes. By contrast, only 3 coding genes and 1 lincRNA were differentially expressed in high CAC versus controls. APOD, encoding a component of high-density lipoprotein, was significantly downregulated in both early MI (FDR = 0.007) and high CAC (FDR = 0.01) compared with controls. CONCLUSIONS: We identified transcriptomic signatures of early MI that include differentially expressed protein-coding genes and lincRNAs, suggesting important roles for protein-coding genes and lincRNAs in the pathogenesis of MI. BioMed Central 2021-02-10 /pmc/articles/PMC7874462/ /pubmed/33568140 http://dx.doi.org/10.1186/s12920-020-00838-2 Text en © The Author(s) 2021 Open AccessThis 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. |
spellingShingle | Research Article Zhang, Xiaoling van Rooij, Jeroen G. J. Wakabayashi, Yoshiyuki Hwang, Shih-Jen Yang, Yanqin Ghanbari, Mohsen Bos, Daniel Levy, Daniel Johnson, Andrew D. van Meurs, Joyce B. J. Kavousi, Maryam Zhu, Jun O’Donnell, Christopher J. Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification |
title | Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification |
title_full | Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification |
title_fullStr | Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification |
title_full_unstemmed | Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification |
title_short | Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification |
title_sort | genome-wide transcriptome study using deep rna sequencing for myocardial infarction and coronary artery calcification |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874462/ https://www.ncbi.nlm.nih.gov/pubmed/33568140 http://dx.doi.org/10.1186/s12920-020-00838-2 |
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