Abstract 15877: The Association Between Atrial Fibrillation-associated Genetic Variants and Electrocardiographic Risk Factors
Introduction: Several single-nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF), but the mechanisms remain unknown. In order to shed potential insight, we sought to determine the relationship between these SNPs and established, potentially mechanistically distinct electrocardiographic (ECG) predictors of AF.
Methods: In Cardiovascular Health Study (CHS) and Atherosclerosis Risk in Communities (ARIC) participants without prevalent AF (CHS: n=3,908; ARIC: n=14,592), we examined the association between five AF-risk SNP and ECG predictor pairs determined a priori based on postulated relationships in the available literature (Table). Logistic regression was used for categorical data and linear regression was used for continuous data, and a two-tailed P value < 0.05 was considered statistically significant. We then undertook a “hypothesis-free” approach to examine all SNP-ECG risk factor relationships, considering a Bonferroni-corrected two-tailed P value < 0.001 as statistically significant. If a SNP-ECG marker relationship was found, the “percent treatment explained” (PTE) method was used to assess the ECG marker as a mediator of the SNP-AF relationship.
Results: In primary analyses, one statistically significant relationship was observed between the rs3807989 SNP and PR interval (Table). However, the PR interval did not appear to mediate the SNP-AF relationship (PTE 25%; CI -7.2 to 963%).
Conclusions: Contrary to hypotheses regarding the mechanisms underlying AF-associated SNPs (such as propensity to atrial ectopy or differences in refractoriness), there was no evidence that established and mechanistically distinct ECG predictors of AF (reflecting atrial ectopy, fibrosis, autonomic tone, and abnormal refractoriness) explain the relationship between these SNPs and AF.
Author Disclosures: K.T. Nguyen: Research Grant; Modest; NIH. J.D. Roberts: None. A. Alonso: None. E.Z. Soliman: None. L.Y. Chen: None. D.E. Arking: None. E. Vittinghoff: None. B.M. Psaty: None. S.R. Heckbert: None. G.M. Marcus: Research Grant; Significant; MedTronic Inc., Pfizer Inc., PCORI. Ownership Interest; Modest; Incarda Therapuetics Inc..
- © 2016 by American Heart Association, Inc.