美国麻省理工学院布罗德研究所和哈佛大学Patrick T. Ellinor团队近期取得重要工作进展，他们对4万人右心结构与功能进行了遗传分析。相关研究成果2022年6月13日在线发表于《自然—遗传学》杂志上。

为了深入了解右心结构和功能，研究人员微调了深度学习模型以识别右心房、右心室和肺动脉，并通过磁共振成像测量了来自英国生物银行的40,000名患者的右心结构。全基因组关联研究确定了130个与至少一个右心测量相关的不同基因座，其中72个与左心结构无关。

在以前与先天性心脏病有关的基因附近发现了一些位点，包括NKX2-5、TBX5/TBX3、WNT9B和GATA4。右心室射血分数的全基因组多基因预测因子与偶发扩张型心肌病相关（风险比，1.33/标准差；P=7.1×10^-13），并且在考虑左心室多基因评分后仍然显著。利用深度学习进行大规模心脏表型分析，他们的结果可以深入了解右心结构和功能的遗传决定因素。

据介绍，先天性心脏病往往涉及进化过程中最近的右心室的发育不良。

附：英文原文

Title: Genetic analysis of right heart structure and function in 40,000 people

Author: Pirruccello, James P., Di Achille, Paolo, Nauffal, Victor, Nekoui, Mahan, Friedman, Samuel F., Klarqvist, Marcus D. R., Chaffin, Mark D., Weng, Lu-Chen, Cunningham, Jonathan W., Khurshid, Shaan, Roselli, Carolina, Lin, Honghuang, Koyama, Satoshi, Ito, Kaoru, Kamatani, Yoichiro, Komuro, Issei, Jurgens, Sean J., Benjamin, Emelia J., Batra, Puneet, Natarajan, Pradeep, Ng, Kenney, Hoffmann, Udo, Lubitz, Steven A., Ho, Jennifer E., Lindsay, Mark E., Philippakis, Anthony A., Ellinor, Patrick T.

Issue&Volume: 2022-06-13

Abstract: Congenital heart diseases often involve maldevelopment of the evolutionarily recent right heart chamber. To gain insight into right heart structure and function, we fine-tuned deep learning models to recognize the right atrium, right ventricle and pulmonary artery, measuring right heart structures in 40,000 individuals from the UK Biobank with magnetic resonance imaging. Genome-wide association studies identified 130 distinct loci associated with at least one right heart measurement, of which 72 were not associated with left heart structures. Loci were found near genes previously linked with congenital heart disease, including NKX2-5, TBX5/TBX3, WNT9B and GATA4. A genome-wide polygenic predictor of right ventricular ejection fraction was associated with incident dilated cardiomyopathy (hazard ratio, 1.33 per standard deviation; P=7.1×1013) and remained significant after accounting for a left ventricular polygenic score. Harnessing deep learning to perform large-scale cardiac phenotyping, our results yield insights into the genetic determinants of right heart structure and function.

DOI: 10.1038/s41588-022-01090-3

Source: https://www.nature.com/articles/s41588-022-01090-3