美国斯坦福大学医学院James R. Priest小组近期取得重要工作进展，他们研究发现升主动脉直径的多基因评分可预测多个人群中胸主动脉瘤的风险。该项研究成果2022年5月30日在线出版于《自然—遗传学》杂志。

在这里，研究人员从来自英国生物库的 36,021 名个体的心脏磁共振图像中自动提取升主动脉直径，然后进行全基因组关联。他们确定了41个位点的先导变异，包括与心血管发育相关的基因（HAND2、TBX20）和孟德尔形式的胸主动脉疾病（ELN、FBN1）。多基因评分显著预测了胸主动脉瘤的普遍风险以及对英国生物库、芬根、宾夕法尼亚大学医学生物库和百万退伍军人计划 (MVP) 内多个血统的胸动脉瘤患者进行手术干预的需求。

此外，研究人员强调了血压在使用孟德尔随机化减少主动脉扩张中的主要因果作用。总体而言，他们的研究结果为使用人体解剖学的遗传决定因素来了解心血管发育，同时改进对胸主动脉疾病的预测提供了一个路线图。

据介绍，主动脉扩大是动脉瘤和夹层的重要危险因素，是发达国家发病率的主要原因。

附：英文原文

Title: High heritability of ascending aortic diameter and trans-ancestry prediction of thoracic aortic disease

Author: Tcheandjieu, Catherine, Xiao, Ke, Tejeda, Helio, Lynch, Julie A., Ruotsalainen, Sanni, Bellomo, Tiffany, Palnati, Madhuri, Judy, Renae, Klarin, Derek, Kember, Rachel L., Verma, Shefali, Palotie, Aarno, Daly, Mark, Ritchie, Marylyn, Rader, Daniel J., Rivas, Manuel A., Assimes, Themistocles, Tsao, Philip, Damrauer, Scott, Priest, James R.

Issue&Volume: 2022-05-30

Abstract: Enlargement of the aorta is an important risk factor for aortic aneurysm and dissection, a leading cause of morbidity in the developed world. Here we performed automated extraction of ascending aortic diameter from cardiac magnetic resonance images of 36,021 individuals from the UK Biobank, followed by genome-wide association. We identified lead variants across 41 loci, including genes related to cardiovascular development (HAND2, TBX20) and Mendelian forms of thoracic aortic disease (ELN, FBN1). A polygenic score significantly predicted prevalent risk of thoracic aortic aneurysm and the need for surgical intervention for patients with thoracic aneurysm across multiple ancestries within the UK Biobank, FinnGen, the Penn Medicine Biobank and the Million Veterans Program (MVP). Additionally, we highlight the primary causal role of blood pressure in reducing aortic dilation using Mendelian randomization. Overall, our findings provide a roadmap for using genetic determinants of human anatomy to understand cardiovascular development while improving prediction of diseases of the thoracic aorta. Trans-ancestry genome-wide analyses identify multiple loci associated with ascending aortic diameter. A polygenic score constructed from these loci predicted prevalent risk of thoracic aortic aneurysm in independent populations.

DOI: 10.1038/s41588-022-01070-7

Source: https://www.nature.com/articles/s41588-022-01070-7