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Genome-Wide Identification of Expression Quantitative Trait Loci (eQTLs) in Human Heart

In recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. The underlying trait-associated variants li...

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Autores principales: Koopmann, Tamara T., Adriaens, Michiel E., Moerland, Perry D., Marsman, Roos F., Westerveld, Margriet L., Lal, Sean, Zhang, Taifang, Simmons, Christine Q., Baczko, Istvan, dos Remedios, Cristobal, Bishopric, Nanette H., Varro, Andras, George, Alfred L., Lodder, Elisabeth M., Bezzina, Connie R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028258/
https://www.ncbi.nlm.nih.gov/pubmed/24846176
http://dx.doi.org/10.1371/journal.pone.0097380
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author Koopmann, Tamara T.
Adriaens, Michiel E.
Moerland, Perry D.
Marsman, Roos F.
Westerveld, Margriet L.
Lal, Sean
Zhang, Taifang
Simmons, Christine Q.
Baczko, Istvan
dos Remedios, Cristobal
Bishopric, Nanette H.
Varro, Andras
George, Alfred L.
Lodder, Elisabeth M.
Bezzina, Connie R.
author_facet Koopmann, Tamara T.
Adriaens, Michiel E.
Moerland, Perry D.
Marsman, Roos F.
Westerveld, Margriet L.
Lal, Sean
Zhang, Taifang
Simmons, Christine Q.
Baczko, Istvan
dos Remedios, Cristobal
Bishopric, Nanette H.
Varro, Andras
George, Alfred L.
Lodder, Elisabeth M.
Bezzina, Connie R.
author_sort Koopmann, Tamara T.
collection PubMed
description In recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. The underlying trait-associated variants likely reside in regulatory regions and exert their effect by modulating gene expression. Hence, the key to unraveling the molecular mechanisms underlying these cardiac traits is to interrogate variants for association with differential transcript abundance by expression quantitative trait locus (eQTL) analysis. In this study we conducted an eQTL analysis of human heart. For a total of 129 left ventricular samples that were collected from non-diseased human donor hearts, genome-wide transcript abundance and genotyping was determined using microarrays. Each of the 18,402 transcripts and 897,683 SNP genotypes that remained after pre-processing and stringent quality control were tested for eQTL effects. We identified 771 eQTLs, regulating 429 unique transcripts. Overlaying these eQTLs with cardiac GWAS loci identified novel candidates for studies aimed at elucidating the functional and transcriptional impact of these loci. Thus, this work provides for the first time a comprehensive eQTL map of human heart: a powerful and unique resource that enables systems genetics approaches for the study of cardiac traits.
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spelling pubmed-40282582014-05-21 Genome-Wide Identification of Expression Quantitative Trait Loci (eQTLs) in Human Heart Koopmann, Tamara T. Adriaens, Michiel E. Moerland, Perry D. Marsman, Roos F. Westerveld, Margriet L. Lal, Sean Zhang, Taifang Simmons, Christine Q. Baczko, Istvan dos Remedios, Cristobal Bishopric, Nanette H. Varro, Andras George, Alfred L. Lodder, Elisabeth M. Bezzina, Connie R. PLoS One Research Article In recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. The underlying trait-associated variants likely reside in regulatory regions and exert their effect by modulating gene expression. Hence, the key to unraveling the molecular mechanisms underlying these cardiac traits is to interrogate variants for association with differential transcript abundance by expression quantitative trait locus (eQTL) analysis. In this study we conducted an eQTL analysis of human heart. For a total of 129 left ventricular samples that were collected from non-diseased human donor hearts, genome-wide transcript abundance and genotyping was determined using microarrays. Each of the 18,402 transcripts and 897,683 SNP genotypes that remained after pre-processing and stringent quality control were tested for eQTL effects. We identified 771 eQTLs, regulating 429 unique transcripts. Overlaying these eQTLs with cardiac GWAS loci identified novel candidates for studies aimed at elucidating the functional and transcriptional impact of these loci. Thus, this work provides for the first time a comprehensive eQTL map of human heart: a powerful and unique resource that enables systems genetics approaches for the study of cardiac traits. Public Library of Science 2014-05-20 /pmc/articles/PMC4028258/ /pubmed/24846176 http://dx.doi.org/10.1371/journal.pone.0097380 Text en © 2014 Koopmann et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Koopmann, Tamara T.
Adriaens, Michiel E.
Moerland, Perry D.
Marsman, Roos F.
Westerveld, Margriet L.
Lal, Sean
Zhang, Taifang
Simmons, Christine Q.
Baczko, Istvan
dos Remedios, Cristobal
Bishopric, Nanette H.
Varro, Andras
George, Alfred L.
Lodder, Elisabeth M.
Bezzina, Connie R.
Genome-Wide Identification of Expression Quantitative Trait Loci (eQTLs) in Human Heart
title Genome-Wide Identification of Expression Quantitative Trait Loci (eQTLs) in Human Heart
title_full Genome-Wide Identification of Expression Quantitative Trait Loci (eQTLs) in Human Heart
title_fullStr Genome-Wide Identification of Expression Quantitative Trait Loci (eQTLs) in Human Heart
title_full_unstemmed Genome-Wide Identification of Expression Quantitative Trait Loci (eQTLs) in Human Heart
title_short Genome-Wide Identification of Expression Quantitative Trait Loci (eQTLs) in Human Heart
title_sort genome-wide identification of expression quantitative trait loci (eqtls) in human heart
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028258/
https://www.ncbi.nlm.nih.gov/pubmed/24846176
http://dx.doi.org/10.1371/journal.pone.0097380
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