Scripps Clinic, La Jolla, CA, 92037, USA.
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Curr Cardiol Rep. 2021 Oct 1;23(11):164. doi: 10.1007/s11886-021-01597-x.
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.
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.
尽管消融和器械技术取得了重大进展，但我们对导致心房颤动 (AF) 的基本细胞和分子因素的理解仍然停滞不前。诊断和预防策略落后于治疗，但 AF 遗传学知识的扩展有可能推动进展。我们旨在回顾了解 AF 的遗传贡献如何指导个体化风险分层和药物发现新途径的方法。
已确定罕见的家族性 AF 形式对 AF 的发展具有单基因贡献。全基因组关联研究 (GWAS) 进一步鉴定了单核苷酸多态性 (SNP)，表明这种常见疾病具有多基因和多效性。多基因风险评分考虑了与疾病相关的众多 SNP，这些 SNP 各自赋予轻度升高的风险，已被开发用于将遗传信息转化为临床实践，尽管仍存在不足之处。此外，最近的遗传发现为新型实验室方法提供了支持，以增强药物发现工作。AF 越来越被认为是一种具有重要遗传成分的疾病。随着测序技术和可及性的扩展，多基因风险评分可以帮助识别高风险个体。基于标准心电图的数字健康工具、人工智能和机器学习的进步以及基于基因组的药物发现的进步可能会整合在一起，在这个强调预防的现代时代提供一种复杂的精准医疗水平。需要进行随机、前瞻性研究来证明这些现有工具的临床益处，以验证这种方法。
