Division of Cardiology, University of California San Francisco, San Francisco, CA, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
Nat Commun. 2024 May 21;15(1):4304. doi: 10.1038/s41467-024-48229-w.
Increased left atrial volume and decreased left atrial function have long been associated with atrial fibrillation. The availability of large-scale cardiac magnetic resonance imaging data paired with genetic data provides a unique opportunity to assess the genetic contributions to left atrial structure and function, and understand their relationship with risk for atrial fibrillation. Here, we use deep learning and surface reconstruction models to measure left atrial minimum volume, maximum volume, stroke volume, and emptying fraction in 40,558 UK Biobank participants. In a genome-wide association study of 35,049 participants without pre-existing cardiovascular disease, we identify 20 common genetic loci associated with left atrial structure and function. We find that polygenic contributions to increased left atrial volume are associated with atrial fibrillation and its downstream consequences, including stroke. Through Mendelian randomization, we find evidence supporting a causal role for left atrial enlargement and dysfunction on atrial fibrillation risk.
左心房容积增加和左心房功能降低与心房颤动长期相关。大规模心脏磁共振成像数据和遗传数据的可用性为评估左心房结构和功能的遗传贡献提供了独特的机会，并有助于理解其与心房颤动风险的关系。在这里，我们使用深度学习和表面重建模型来测量 40558 名英国生物库参与者的左心房最小容积、最大容积、心搏量和排空分数。在一项针对 35049 名无先前心血管疾病参与者的全基因组关联研究中，我们确定了 20 个与左心房结构和功能相关的常见遗传位点。我们发现，左心房容积增加的多基因贡献与心房颤动及其下游后果（包括中风）有关。通过孟德尔随机化，我们发现左心房扩大和功能障碍对心房颤动风险有因果作用的证据。
