Abstract 18089: Shared Single Nucleotide Polymorphisms May Explain the Relationship Between Clusters of Comorbid Risk Factors and Incident Heart Failure in the Framingham Heart Study
Introduction: Multiple single nucleotide polymorphisms (SNPs) directly related to myocardial function have been implicated in congestive heart failure (CHF). Polymorphisms related to non-cardiac risk factors for CHF remain incompletely described.
Hypothesis: CHF risk factors reflect shared genetic determinants with CHF.
Methods: Participants from the Framingham Heart Study Original and Offspring cohorts underwent genotyping using the Affymetrix GeneChip Human Mapping 100k set. In total 1345 subjects were included in this analysis. Incident heart failure was defined as any hospitalization or history of clinical CHF during routine exam visits that was not present at baseline. Family-based association testing (FBAT) was performed to identify SNPs associated with incident CHF. SNPs with an FBAT p-value <0.0025 were analyzed using an SNP-specific extension of RenoDOI, a Cytoscape-based knowledge-based visual analysis platform.
Results: Incident CHF occurred in a total of 73 (5.4%) subjects. A total of 277 SNPs were associated with incident HF at a p-value < 0.0025. Among these were clusters of 3 SNPs in each of 2 genes were associated both with CHF and other previously observed CHF risk factors. The first cluster of 3 SNPs was associated with the RAR-related Orphan Receptor A (RORA) gene, which regulates circadian rhythm clock genes, cholesterol metabolism, and hypoxia-inducible factor 1A, all of which have been implicated in HF pathogenesis. The second cluster of 3 SNPs were associated with Cadherin-Like and PC-Esterase Domain Containing 1 (CPED1), a poorly studied protein, which has been associated with anxiety, autism spectrum disorders, and blood pressure regulation in some population.
Conclusions: Some SNPs associated with CHF may be related to CHF risk factors as well, suggesting that some of these risk factors are explained by shared genetic abnormalities in addition to or instead of a direct pathophysiologic mechanisms.
Author Disclosures: L. Stevens: None. M.A. Hinterberg: None. C. Goerg: None. D.P. Kao: None.
- © 2016 by American Heart Association, Inc.