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Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke
Atrial fibrillation (AF) is a common cardiac arrhythmia and is one of the major causes of ischemic stroke. In addition to the clinical factors such as CHADS2 or CHADS2-VASC score, the impact of genetic factors on the risk of thromboembolic stroke in patients with AF has been largely unknown. Single-...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463198/ https://www.ncbi.nlm.nih.gov/pubmed/30857284 http://dx.doi.org/10.3390/jcm8030332 |
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author | Hsieh, Chia-Shan Huang, Pang-Shuo Chang, Sheng-Nan Wu, Cho-Kai Hwang, Juey-Jen Chuang, Eric Y. Tsai, Chia-Ti |
author_facet | Hsieh, Chia-Shan Huang, Pang-Shuo Chang, Sheng-Nan Wu, Cho-Kai Hwang, Juey-Jen Chuang, Eric Y. Tsai, Chia-Ti |
author_sort | Hsieh, Chia-Shan |
collection | PubMed |
description | Atrial fibrillation (AF) is a common cardiac arrhythmia and is one of the major causes of ischemic stroke. In addition to the clinical factors such as CHADS2 or CHADS2-VASC score, the impact of genetic factors on the risk of thromboembolic stroke in patients with AF has been largely unknown. Single-nucleotide polymorphisms in several genomic regions have been found to be associated with AF. However, these loci do not contribute to all the genetic risks of AF or AF related thromboembolic risks, suggesting that there are other genetic factors or variants not yet discovered. In the human genome, copy number variations (CNVs) could also contribute to disease susceptibility. In the present study, we sought to identify CNVs determining the AF-related thromboembolic risk. Using a genome-wide approach in 109 patients with AF and thromboembolic stroke and 14,666 controls from the Taiwanese general population (Taiwan Biobank), we first identified deletions in chromosomal regions 1p36.32-1p36.33, 5p15.33, 8q24.3 and 19p13.3 and amplifications in 14q11.2 that were significantly associated with AF-related stroke in the Taiwanese population. In these regions, 148 genes were involved, including several microRNAs and long non-recoding RNAs. Using a pathway analysis, we found deletions in GNB1, PRKCZ, and GNG7 genes related to the alpha-adrenergic receptor signaling pathway that play a major role in determining the risk of an AF-related stroke. In conclusion, CNVs may be genetic predictors of a risk of a thromboembolic stroke for patients with AF, possibly pointing to an impaired alpha-adrenergic signaling pathway in the mechanism of AF-related thromboembolism. |
format | Online Article Text |
id | pubmed-6463198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64631982019-04-19 Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke Hsieh, Chia-Shan Huang, Pang-Shuo Chang, Sheng-Nan Wu, Cho-Kai Hwang, Juey-Jen Chuang, Eric Y. Tsai, Chia-Ti J Clin Med Article Atrial fibrillation (AF) is a common cardiac arrhythmia and is one of the major causes of ischemic stroke. In addition to the clinical factors such as CHADS2 or CHADS2-VASC score, the impact of genetic factors on the risk of thromboembolic stroke in patients with AF has been largely unknown. Single-nucleotide polymorphisms in several genomic regions have been found to be associated with AF. However, these loci do not contribute to all the genetic risks of AF or AF related thromboembolic risks, suggesting that there are other genetic factors or variants not yet discovered. In the human genome, copy number variations (CNVs) could also contribute to disease susceptibility. In the present study, we sought to identify CNVs determining the AF-related thromboembolic risk. Using a genome-wide approach in 109 patients with AF and thromboembolic stroke and 14,666 controls from the Taiwanese general population (Taiwan Biobank), we first identified deletions in chromosomal regions 1p36.32-1p36.33, 5p15.33, 8q24.3 and 19p13.3 and amplifications in 14q11.2 that were significantly associated with AF-related stroke in the Taiwanese population. In these regions, 148 genes were involved, including several microRNAs and long non-recoding RNAs. Using a pathway analysis, we found deletions in GNB1, PRKCZ, and GNG7 genes related to the alpha-adrenergic receptor signaling pathway that play a major role in determining the risk of an AF-related stroke. In conclusion, CNVs may be genetic predictors of a risk of a thromboembolic stroke for patients with AF, possibly pointing to an impaired alpha-adrenergic signaling pathway in the mechanism of AF-related thromboembolism. MDPI 2019-03-09 /pmc/articles/PMC6463198/ /pubmed/30857284 http://dx.doi.org/10.3390/jcm8030332 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hsieh, Chia-Shan Huang, Pang-Shuo Chang, Sheng-Nan Wu, Cho-Kai Hwang, Juey-Jen Chuang, Eric Y. Tsai, Chia-Ti Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke |
title | Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke |
title_full | Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke |
title_fullStr | Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke |
title_full_unstemmed | Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke |
title_short | Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke |
title_sort | genome-wide copy number variation association study of atrial fibrillation related thromboembolic stroke |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463198/ https://www.ncbi.nlm.nih.gov/pubmed/30857284 http://dx.doi.org/10.3390/jcm8030332 |
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