Abstract 17027: Expression Quantitative Trait Locus (eQTL) Map for Genetic Variants Associated With Cardiovascular Traits in Human Heart
Introduction: To identify genetic variants that may influence disease susceptibility by modulating gene expression, this study investigated associations between genetic variants associated with cardiovascular traits and gene expression in heart tissue.
Methods: In left ventricle from 102 heart donors with no diagnosed heart disease and 100 heart transplant patients (explanted failed hearts), genotyping was performed with Illumina CardioMetabo Chips (covering ~200,000 variants associated with cardiovascular and metabolic traits). Gene expression profiles for each tissue sample were generated with Affymetrix Human Gene ST 1.0 microarrays. Associations between genotype and gene expression (expression quantitative trait loci, eQTLs) were tested with an additive genetic model, adjusted for multiple comparisons. For each gene, proximal (cis) and distal (trans) eQTL effects were tested by analyzing variants <1Mb and >1Mb from the transcription start site, respectively.
Results: After quality control filtering, 30,412 genes were tested for association with 54,908 variants in donors and 56,976 variants in transplant patients. In donors, 275 genes with cis-eQTL effects and 100 genes with trans-eQTL effects were identified (adjusted p<0.05, effect size: 0.1-1.8). In patients, 244 genes with cis-eQTL effects and 101 genes with trans-eQTL effects were identified (adjusted p<0.05, effect size: 0.1-1.3). Fewer than half the genes with cis-eQTL effects (n=115) were shared by donors and transplant patients.
Conclusions: This study provides the first eQTL map of disease-associated variants in established heart disease. These data may help identify functional non-coding variants that contribute to susceptibility to disease.
Figure: Upper panel, Manhattan plot of genes with cis-eQTL (dark blue) and trans-eQTL (light blue) effects in heart donors (top) and transplant patients (bottom). Lower panel, example cis-eQTL shared by donors and transplant patients.
Author Disclosures: N.E. Wheeler: None. V.A. Cameron: None. J.F. Pearson: None. P.P. Gardener: None. C.S. Moravec: None. W.E. Sweet: None. W.W. Tang: None. R.W. Troughton: None. A.M. Richards: None. A.P. Pilbrow: None.
- © 2015 by American Heart Association, Inc.