Abstract
Background: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Results: 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. Conclusions: 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.
| Original language | English (US) |
|---|---|
| Article number | 170 |
| Journal | Genome Biology |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 14 2017 |
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Keywords
- Dilated cardiomyopathy
- EQTL
- Gene expression
- Genetics
- Heart
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Genetics
- Cell Biology
Cite this
Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy. / Heinig, Matthias; Adriaens, Michiel E.; Schafer, Sebastian; van Deutekom, Hanneke W.M.; Lodder, Elisabeth M.; Ware, James S.; Schneider, Valentin; Felkin, Leanne E.; Creemers, Esther E.; Meder, Benjamin; Katus, Hugo A.; Rühle, Frank; Stoll, Monika; Cambien, François; Villard, Eric; Charron, Philippe; Varro, Andras; Bishopric, Nanette; George, Alfred L.; dos Remedios, Cristobal; Moreno-Moral, Aida; Pesce, Francesco; Bauerfeind, Anja; Rüschendorf, Franz; Rintisch, Carola; Petretto, Enrico; Barton, Paul J.; Cook, Stuart A.; Pinto, Yigal M.; Bezzina, Connie R.; Hubner, Norbert.
In: Genome Biology, Vol. 18, No. 1, 170, 14.09.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy
AU - Heinig, Matthias
AU - Adriaens, Michiel E.
AU - Schafer, Sebastian
AU - van Deutekom, Hanneke W.M.
AU - Lodder, Elisabeth M.
AU - Ware, James S.
AU - Schneider, Valentin
AU - Felkin, Leanne E.
AU - Creemers, Esther E.
AU - Meder, Benjamin
AU - Katus, Hugo A.
AU - Rühle, Frank
AU - Stoll, Monika
AU - Cambien, François
AU - Villard, Eric
AU - Charron, Philippe
AU - Varro, Andras
AU - Bishopric, Nanette
AU - George, Alfred L.
AU - dos Remedios, Cristobal
AU - Moreno-Moral, Aida
AU - Pesce, Francesco
AU - Bauerfeind, Anja
AU - Rüschendorf, Franz
AU - Rintisch, Carola
AU - Petretto, Enrico
AU - Barton, Paul J.
AU - Cook, Stuart A.
AU - Pinto, Yigal M.
AU - Bezzina, Connie R.
AU - Hubner, Norbert
PY - 2017/9/14
Y1 - 2017/9/14
N2 - Background: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Results: 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. Conclusions: 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.
AB - Background: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Results: 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. Conclusions: 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.
KW - Dilated cardiomyopathy
KW - EQTL
KW - Gene expression
KW - Genetics
KW - Heart
UR - http://www.scopus.com/inward/record.url?scp=85029430721&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029430721&partnerID=8YFLogxK
U2 - 10.1186/s13059-017-1286-z
DO - 10.1186/s13059-017-1286-z
M3 - Article
C2 - 28903782
AN - SCOPUS:85029430721
VL - 18
JO - Genome Biology
JF - Genome Biology
SN - 1465-6914
IS - 1
M1 - 170
ER -