@article{ffcba53abd3a4ed8a08063f9b9755e84,
title = "Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy",
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 = "Dilated cardiomyopathy, EQTL, Gene expression, Genetics, Heart",
author = "Matthias Heinig and Adriaens, {Michiel E.} and Sebastian Schafer and {van Deutekom}, {Hanneke W.M.} and Lodder, {Elisabeth M.} and Ware, {James S.} and Valentin Schneider and Felkin, {Leanne E.} and Creemers, {Esther E.} and Benjamin Meder and Katus, {Hugo A.} and Frank R{\"u}hle and Monika Stoll and Fran{\c c}ois Cambien and Eric Villard and Philippe Charron and Andras Varro and Bishopric, {Nanette H.} and George, {Alfred L.} and {dos Remedios}, Cristobal and Aida Moreno-Moral and Francesco Pesce and Anja Bauerfeind and Franz R{\"u}schendorf and Carola Rintisch and Enrico Petretto and Barton, {Paul J.} and Cook, {Stuart A.} and Pinto, {Yigal M.} and Bezzina, {Connie R.} and Norbert Hubner",
note = "Funding Information: This work was supported by funding to MH by the Federal Ministry of Education and Research (BMBF, Germany) in the project eMed:symAtrial (01ZX1408D), funding by the Federal Ministry of Education and Research (BMBF, Germany) in the project NGFNPlus (01GS084) to MS. CRB and EML were supported by the Netherlands Heart Foundation PREDICT project (CVON 2012-10). EP and AM are supported by Duke-National University of Singapore (NUS) Medical School and the Singapore Ministry of Health. MEA{\textquoteright}s work at the Maastricht Centre for Systems Biology is supported by the Dutch Province of Limburg. SAC, PJB, and JSW were supported by the Wellcome Trust, British Heart Foundation, NIHR CV BRU of Royal Brompton and Harefield, NHS Foundation Trust, Leducq Foundation, and the MRC UK. In addition SAC was supported by NMRC Singapore, Goh Foundation and Tanoto Foundation. NH is supported by the Helmholtz Alliance ICEMED. FP was funded by European Union FP7 [ERG-239158, CardioNeT-ITN-289600]. EV was supported by the European Union (FP7 BestAgeing). NHB was supported by NHLBI (NIH R01 HL071094), the Miami Heart Research Institute, and the Leducq Network “alliance against sudden death”. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = sep,
day = "14",
doi = "10.1186/s13059-017-1286-z",
language = "English (US)",
volume = "18",
journal = "Genome Biology",
issn = "1465-6914",
publisher = "BioMed Central",
number = "1",
}