As the most common cardiac arrhythmia, atrial fibrillation (AF) is a major risk factor for stroke, heart failure, and premature death with considerable associated costs. However, no available treatment options have optimal benefit-harm profiles currently, reflecting an incomplete understanding of the biological mechanisms underlying this complex arrhythmia. Recently, molecular epidemiological studies, especially genome-wide association studies, have emphasized the substantial genetic component of AF etiology. A comprehensive mapping of the genetic underpinnings for AF can expand our knowledge of AF mechanism and further facilitate the process of locating novel therapeutics for AF. Here we provide a state-of-the-art review of the molecular genetics of AF incorporating evidence from linkage analysis and candidate gene, as well as genome-wide association studies of common variations and rare copy number variations; potential epigenetic modifications (e.g., DNA methylation, histone modification, and non-coding RNAs) are also involved. We also outline the challenges in mechanism investigation and potential future directions in this article.

作为最常见的心律不齐，房颤（AF）是中风，心力衰竭和过早死亡的主要危险因素，相关费用也很高。然而，目前尚无可用的治疗方案具有最佳的利弊关系，这反映出对该复杂心律不齐的生物学机制的不完全了解。最近，分子流行病学研究，尤其是全基因组关联研究，已经强调了AF病因的重要遗传成分。对AF遗传基础的全面定位可以扩展我们对AF机制的知识，并进一步促进寻找AF新疗法的过程。在这里，我们提供了AF分子遗传学的最新综述，其中包括了连锁分析和候选基因的证据，以及常见变异和稀有拷贝数变异的全基因组关联研究；还涉及潜在的表观遗传修饰（例如DNA甲基化，组蛋白修饰和非编码RNA）。我们还将在本文中概述机制研究中的挑战和潜在的未来方向。