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Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue

BACKGROUND: Both ambulatory atrial fibrillation (AF) and post-operative AF (poAF) are associated with substantial morbidity and mortality. Analyzing the tissue-specific gene expression in the left atrium (LA) can identify novel genes associated with AF and further the understanding of the mechanism...

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Autores principales: Sigurdsson, Martin I, Saddic, Louis, Heydarpour, Mahyar, Chang, Tzuu-Wang, Shekar, Prem, Aranki, Sary, Couper, Gregory S, Shernan, Stanton K., Muehlschlegel, Jochen D., Body, Simon C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414158/
https://www.ncbi.nlm.nih.gov/pubmed/28464817
http://dx.doi.org/10.1186/s12920-017-0270-5
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author Sigurdsson, Martin I
Saddic, Louis
Heydarpour, Mahyar
Chang, Tzuu-Wang
Shekar, Prem
Aranki, Sary
Couper, Gregory S
Shernan, Stanton K.
Muehlschlegel, Jochen D.
Body, Simon C.
author_facet Sigurdsson, Martin I
Saddic, Louis
Heydarpour, Mahyar
Chang, Tzuu-Wang
Shekar, Prem
Aranki, Sary
Couper, Gregory S
Shernan, Stanton K.
Muehlschlegel, Jochen D.
Body, Simon C.
author_sort Sigurdsson, Martin I
collection PubMed
description BACKGROUND: Both ambulatory atrial fibrillation (AF) and post-operative AF (poAF) are associated with substantial morbidity and mortality. Analyzing the tissue-specific gene expression in the left atrium (LA) can identify novel genes associated with AF and further the understanding of the mechanism by which previously identified genetic variants associated with AF mediate their effects. METHODS: LA free wall samples were obtained intraoperatively immediately prior to mitral valve surgery in 62 Caucasian individuals. Gene expression was quantified on mRNA harvested from these samples using RNA sequencing. An expression quantitative trait loci (eQTL) analysis was performed, comparing gene expression between different genotypes of 1.0 million genetic markers, emphasizing genomic regions and genes associated with AF. RESULTS: Comparison of whole-genome expression between patients who later developed poAF and those who did not identified 23 differentially expressed genes. These included genes associated with the resting membrane potential modified by potassium currents, as well as genes within Wnt signaling and cyclic GMP metabolism. The eQTL analysis identified 16,139 cis eQTL relationships in the LA, including several involving genes and single nucleotide polymorphisms (SNPs) linked to AF. A previous relationship between rs3744029 and MYOZ1 expression was confirmed, and a novel relationship between rs6795970 and the expression of the SCN10A gene was identified. CONCLUSIONS: The current study is the first analysis of the human LA expression landscape using high-throughput RNA sequencing. Several novel genes and variants likely involved in AF pathogenesis were identified, thus furthering the understanding of how variants associated with AF mediate their effects via altered gene expression. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00833313, registered 5. January 2009 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-017-0270-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-54141582017-05-03 Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue Sigurdsson, Martin I Saddic, Louis Heydarpour, Mahyar Chang, Tzuu-Wang Shekar, Prem Aranki, Sary Couper, Gregory S Shernan, Stanton K. Muehlschlegel, Jochen D. Body, Simon C. BMC Med Genomics Research Article BACKGROUND: Both ambulatory atrial fibrillation (AF) and post-operative AF (poAF) are associated with substantial morbidity and mortality. Analyzing the tissue-specific gene expression in the left atrium (LA) can identify novel genes associated with AF and further the understanding of the mechanism by which previously identified genetic variants associated with AF mediate their effects. METHODS: LA free wall samples were obtained intraoperatively immediately prior to mitral valve surgery in 62 Caucasian individuals. Gene expression was quantified on mRNA harvested from these samples using RNA sequencing. An expression quantitative trait loci (eQTL) analysis was performed, comparing gene expression between different genotypes of 1.0 million genetic markers, emphasizing genomic regions and genes associated with AF. RESULTS: Comparison of whole-genome expression between patients who later developed poAF and those who did not identified 23 differentially expressed genes. These included genes associated with the resting membrane potential modified by potassium currents, as well as genes within Wnt signaling and cyclic GMP metabolism. The eQTL analysis identified 16,139 cis eQTL relationships in the LA, including several involving genes and single nucleotide polymorphisms (SNPs) linked to AF. A previous relationship between rs3744029 and MYOZ1 expression was confirmed, and a novel relationship between rs6795970 and the expression of the SCN10A gene was identified. CONCLUSIONS: The current study is the first analysis of the human LA expression landscape using high-throughput RNA sequencing. Several novel genes and variants likely involved in AF pathogenesis were identified, thus furthering the understanding of how variants associated with AF mediate their effects via altered gene expression. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00833313, registered 5. January 2009 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-017-0270-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-02 /pmc/articles/PMC5414158/ /pubmed/28464817 http://dx.doi.org/10.1186/s12920-017-0270-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
spellingShingle Research Article
Sigurdsson, Martin I
Saddic, Louis
Heydarpour, Mahyar
Chang, Tzuu-Wang
Shekar, Prem
Aranki, Sary
Couper, Gregory S
Shernan, Stanton K.
Muehlschlegel, Jochen D.
Body, Simon C.
Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue
title Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue
title_full Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue
title_fullStr Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue
title_full_unstemmed Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue
title_short Post-operative atrial fibrillation examined using whole-genome RNA sequencing in human left atrial tissue
title_sort post-operative atrial fibrillation examined using whole-genome rna sequencing in human left atrial tissue
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414158/
https://www.ncbi.nlm.nih.gov/pubmed/28464817
http://dx.doi.org/10.1186/s12920-017-0270-5
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