Cardiology Division, Massachusetts General Hospital, Boston, MA, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Nat Genet. 2022 Jun;54(6):792-803. doi: 10.1038/s41588-022-01090-3. Epub 2022 Jun 13.
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 × 10) 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.
先天性心脏病通常涉及进化较新的右心腔的发育不良。为了深入了解右心结构和功能，我们对深度学习模型进行了微调，以识别右心房、右心室和肺动脉，并使用磁共振成像对英国生物库中的 40,000 个人的右心结构进行了测量。全基因组关联研究确定了 130 个与至少一个右心测量值相关的独特位点，其中 72 个位点与左心结构无关。这些位点位于先前与先天性心脏病相关的基因附近，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扩张型心肌病的发病相关（危险比，每标准差 1.33；P=7.1×10），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，我们的研究结果深入了解了右心结构和功能的遗传决定因素。
