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Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy

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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 Name:Heinig, M. and Adriaens, M.E. and Schafer, S. and van Deutekom, H.W.M. and Lodder, E.M. and Ware, J.S. and Schneider, V. and Felkin, L.E. and Creemers, E.E. and Meder, B. and Katus, H.A. and Ruehle, F. and Stoll, M. and Cambien, F. and Villard, E. and Charron, P. and Varro, A. and Bishopric, N.H. and George, A.L. and Dos Remedios, C. and Moreno-Moral, A. and Pesce, F. and Bauerfeind, A. and Rueschendorf, F. and Rintisch, C. and Petretto, E. and Barton, P.J. and Cook, S.A. and Pinto, Y.M. and Bezzina, C.R. and Hubner, N.
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 (U.K.)
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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