Abstract 16379: DNA Methylation Profiling Identifies Novel Epigenetic Markers of Cardiovascular Events
Objectives: Considerable effort has been made in identifying the genetic underpinnings of cardiovascular disease (CVD), including cardiovascular events. However, DNA variation does not fully account for all heritable factors of CVD risk or early mortality. DNA methylation is a non-DNA sequence-based, heritable form of gene regulation that plays a role in CVD. To identify the role of epigenetic variation in CVD we performed DNA methylation profiling in a CVD cohort (CATHGEN).
Methods: The study population included individuals from the CATHGEN biorepository referred for cardiac catheterization for concern of ischemic heart disease. Cases were defined as individuals who died >580 days (N=62) after index cath. and controls were alive and without any CVD events for >1700 days (N=49) after index cath. We used Illumina’s HumanMethylation450 array to profile the methylation status of 485,000 CpG dinucleotides. After QC, preprocessing, normalization, and removal of cross-reactive probes, we logit-transformed the resulting β-values of the remaining 445,323 probes. We tested for association between methylation and case-control status using a linear model, adjusting for age, race, sex, row and chip. Follow-up was based either on the resulting p-value for association between methylation and case-control status (p>0.001, n=1438 probes), or a threshold for the difference between average methylation status in cases and controls (
Author Disclosures: S.H. Shah: None. L.C. Kwee: None. E.A. Grass: None. W.E. Kraus: None. S.G. Gregory: None.
- © 2014 by American Heart Association, Inc.