Journal
CURRENT CARDIOLOGY REPORTS
Volume 23, Issue 11, Pages -Publisher
SPRINGER
DOI: 10.1007/s11886-021-01597-x
Keywords
Atrial fibrillation; Genetics; Polygenic risk; Translation; Drug discovery
Categories
Funding
- NCATS/NIH [UL1TR002550]
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Understanding the genetic contributions to AF is crucial for personalized risk stratification and drug discovery, but current polygenic risk scores have limitations that require further research and improvement. By integrating digital health tools, artificial intelligence, and genomic-driven drug discovery, a sophisticated level of precision medicine can be delivered in the modern era of emphasis on prevention.
Purpose of Review Our understanding of the fundamental cellular and molecular factors leading to atrial fibrillation (AF) remains stagnant despite significant advancement in ablation and device technologies. Diagnosis and prevention strategies fall behind that of treatment, but expanding knowledge in AF genetics holds the potential to drive progress. We aim to review how an understanding of the genetic contributions to AF can guide an approach to individualized risk stratification and novel avenues in drug discovery. Recent Findings Rare familial forms of AF identified monogenic contributions to the development of AF. Genome-wide association studies (GWAS) further identified single-nucleotide polymorphisms (SNPs) suggesting polygenic and multiplex nature of this common disease. Polygenic risk scores accounting for the multitude of associated SNPs that each confer mildly elevated risk have been developed to translate genetic information into clinical practice, though shortcomings remain. Additionally, novel laboratory methods have been empowered by recent genetic findings to enhance drug discovery efforts. AF is increasingly recognized as a disease with a significant genetic component. With expanding sequencing technologies and accessibility, polygenic risk scores can help identify high risk individuals. Advancement in digital health tools, artificial intelligence and machine learning based on standard electrocardiograms, and genomic driven drug discovery may be integrated to deliver a sophisticated level of precision medicine in this modern era of emphasis on prevention. Randomized, prospective studies to demonstrate clinical benefits of these available tools are needed to validate this approach.
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