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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-...

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Autores principales: Hsieh, Chia-Shan, Huang, Pang-Shuo, Chang, Sheng-Nan, Wu, Cho-Kai, Hwang, Juey-Jen, Chuang, Eric Y., Tsai, Chia-Ti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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