As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous blood delivery to peripheral arteries. Distension during systole and recoil during diastole conserves ventricular energy and is enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and prematurely in vascular disease. To discover genetic determinants of aortic distensibility we trained a deep learning model to quantify aortic size throughout the cardiac cycle and calculate aortic distensibility and aortic strain in 42,342 participants in the UK Biobank with available cardiac magnetic resonance imaging. In up to 40,028 participants with genetic data, common variant analysis identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were specific to strain or distensibility and were not identified in a thoracic aortic diameter GWAS within the same samples. Loci associated with both aortic diameter and aortic strain or distensibility demonstrated a consistent, inverse directionality. Transcriptome-wide analyses, rare-variant burden tests, and analyses of gene expression in single nucleus RNA sequencing of human aorta were performed to prioritize genes at individual loci. Loci highlighted multiple genes involved in elastogenesis, matrix degradation, and extracellular polysaccharide generation. Characterization of the genetic determinants of aortic function may provide novel targets for medical intervention in aortic disease.

中文翻译：

---

主动脉扩张的遗传决定因素

作为最大的导管，主动脉负责将来自心室射血的阶段性收缩流入转化为更连续的血液输送至外周动脉。收缩期的扩张和舒张期的回缩保存心室能量，并通过主动脉细胞外基质的特殊成分实现。主动脉扩张性随着年龄的增长而降低，并且在血管疾病中过早出现。为了发现主动脉扩张性的遗传决定因素，我们训练了一个深度学习模型来量化整个心动周期的主动脉大小，并使用可用的心脏磁共振成像计算英国生物银行 42,342 名参与者的主动脉扩张性和主动脉应变。在多达 40,028 名具有基因数据的参与者中，常见变异分析分别确定了 12 个和 26 个位点用于升主动脉扩张和 11 个和 21 个位点用于降主动脉扩张性和应变。在新发现的基因座中，有 22 个对应变或扩张性具有特异性，并且在相同样本的胸主动脉直径 GWAS 中未发现。与主动脉直径和主动脉应变或扩张性相关的位点表现出一致的反向方向性。在人类主动脉的单核 RNA 测序中进行全转录组分析、罕见变异负荷测试和基因表达分析，以优先考虑单个基因座的基因。Loci 强调了涉及弹性生成、基质降解和细胞外多糖生成的多个基因。