Title |
Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy
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Published in |
Genome Biology, September 2017
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DOI | 10.1186/s13059-017-1286-z |
Pubmed ID | |
Authors |
Matthias Heinig, Michiel E. Adriaens, Sebastian Schafer, Hanneke W. M. van Deutekom, Elisabeth M. Lodder, James S. Ware, Valentin Schneider, Leanne E. Felkin, Esther E. Creemers, Benjamin Meder, Hugo A. Katus, Frank Rühle, Monika Stoll, François Cambien, Eric Villard, Philippe Charron, Andras Varro, Nanette H. Bishopric, Alfred L. George, Cristobal dos Remedios, Aida Moreno-Moral, Francesco Pesce, Anja Bauerfeind, Franz Rüschendorf, Carola Rintisch, Enrico Petretto, Paul J. Barton, Stuart A. Cook, Yigal M. Pinto, Connie R. Bezzina, Norbert Hubner |
Abstract |
Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage, and allele-specific expression. Systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome-wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome-wide association signals in two independent cohorts. RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics. |
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Country | Count | As % |
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United States | 6 | 23% |
United Kingdom | 5 | 19% |
Netherlands | 4 | 15% |
France | 2 | 8% |
Canada | 2 | 8% |
Australia | 1 | 4% |
India | 1 | 4% |
Germany | 1 | 4% |
Unknown | 4 | 15% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 14 | 54% |
Scientists | 6 | 23% |
Practitioners (doctors, other healthcare professionals) | 4 | 15% |
Science communicators (journalists, bloggers, editors) | 2 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 127 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 31 | 24% |
Student > Ph. D. Student | 20 | 16% |
Student > Master | 11 | 9% |
Student > Doctoral Student | 8 | 6% |
Student > Bachelor | 6 | 5% |
Other | 13 | 10% |
Unknown | 38 | 30% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 35 | 28% |
Medicine and Dentistry | 21 | 17% |
Agricultural and Biological Sciences | 14 | 11% |
Computer Science | 6 | 5% |
Psychology | 3 | 2% |
Other | 8 | 6% |
Unknown | 40 | 31% |