Genetic Contribution to AF
It is now well recognized that AF is heritable.21,22,23 Individuals having a first-degree relative with AF have approximately a 40% increased risk for development of AF after accounting for established clinical AF risk factors.23 In the last decade, great progress has been made in identifying the genetic determinants of AF. Although studies of families with AF have led to the identification of mutations in a series of ion channels and molecules, these mutations are typically family-specific, rare, and do not explain a significant portion of the heritability of AF.24 Therefore, population-based or genome-wide studies have been used to identify many AF risk loci.25,26,27,28,29,30 The genes at these loci encode transcription factors and ion channels, and many are without a clear relation to AF at the present time.
There is interest in trying to use genetics to predict the onset of AF, to stratify the risk of AF outcomes such as stroke and HF, and to identify the response to treatments including antiarrhythmic medications or catheter ablation procedures. Interestingly, a genetic risk score consisting of the top 12 loci for AF can be used to identify as much as a 5-fold gradient in the risk of AF or those at greatest risk for a stroke.31,32 However, similar to other common diseases, the genetic risk for AF provides minimal additional predictive value after considering basic clinical risk factors such as age and sex.33,34 Future studies will be directed at using a comprehensive panel of genetic variants to identify those at greatest risk for AF, and also to predict stroke risk and outcomes to AF therapy, including AF ablation.35 Whether genetic testing will ultimately prove to be an important clinical marker of AF risk will become clear over time. An alternative and/or complementary strategy, which might be easier for clinicians to employ, will be the use of a clinical risk score.