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.