Gene-Gene and Gene-Environment Interactions in Atrial Fibrillation
Atrial fibrillation (AF) is the most common sustained arrhythmia, reaching epidemic proportions in the aging population and causing considerable morbidity, mortality, and socioeconomic burden. Clinical and basic investigations suggest that AF arises from the interaction between inherited and environmental risk factors. Although genetic risk variants for AF have been identified, very little has been reported on whether gene-gene and gene-environment interactions influence the risk of AF. Addressing this knowledge gap will ultimately enhance prediction of AF.
This project examines interactions between single nucleotide polymorphisms (SNPs) in known AF genes, and interactions between these genetic risk variants with environmental risk factors in modifying AF susceptibility. These genes include those encoding the cardiac sodium channel and components of the renin-angiotensin system. This work will leverage the extensive genotype and phenotype data from the Candidate Gene Association Resource (CARe) cohorts, which include Atherosclerosis Risk in Communities and Framingham Heart Study. The specific aims of this project are to: identify significant interactions among SNPs in known AF genes; identify significant interactions between SNPs in known AF genes and environmental risk factors; identify significant interactions between environmental risk factors and SNPs in genes currently not known to be associated with AF; replicate significant interactions in independent samples.
By taking advantage of valuable existing NIH resources (genotype and phenotype data from the CARe cohorts), this project will advance the understanding of the genetics of AF by exploring directions that were not previously possible, namely gene-gene and gene-environment interactions. Ultimately, a better understanding of the genetics of AF will translate to a mechanism-based and personalized approach to prevent and treat this common public health problem.