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| Item Type: | Article |
|---|---|
| Title: | Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy |
| Creators: |
Heinig, M.  ORCID: https://orcid.org/0000-0002-5612-1720, Adriaens, M.E., Schafer, S., van Deutekom, H.W.M., Lodder, E.M., Ware, J.S., Schneider, V. ORCID: https://orcid.org/0000-0002-3980-3789, Felkin, L.E., Creemers, E.E., Meder, B., Katus, H.A., Rühle, F., Stoll, M., Cambien, F., Villard, E., Charron, P., Varro, A., Bishopric, N.H., George, A.L., Dos Remedios, C., Moreno-Moral, A., Pesce, F., Bauerfeind, A., Rüschendorf, F. ORCID: https://orcid.org/0000-0001-5640-810X, Rintisch, C., Petretto, E., Barton, P.J., Cook, S.A., Pinto, Y.M., Bezzina, C.R. and Hubner, N. ORCID: https://orcid.org/0000-0002-1218-6223
|
| 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. |
| Keywords: | Genetics, Gene Expression, eQTL, Dilated Cardiomyopathy, Heart |
| Source: | Genome Biology |
| ISSN: | 1474-760X |
| Publisher: | BioMed Central |
| Volume: | 18 |
| Number: | 1 |
| Page Range: | 170 |
| Date: | 14 September 2017 |
| Official Publication: | https://doi.org/10.1186/s13059-017-1286-z |
| PubMed: | View item in PubMed |
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