英国伦敦玛丽女王大学Patricia B. Munroe和Steffen E. Petersen共同合作，近期取得重要工作进展，他们通过全基因组关联分析揭示了右心室结构和功能的遗传结构。该项研究成果2022年6月13日在线出版于《自然—遗传学》杂志上。

在这里，研究人员对心血管磁共振图像的四种临床相关右心室（RV）表型（RV舒张末期容积、RV收缩末期容积、RV每搏输出量、RV射血分数）进行全基因组关联分析，在29,506 名英国生物银行参与者中使用了最先进的深度学习算法。研究人员确定了25个与至少一种RV表型相关的、P<2.27×10^-8的独特基因座，其中17个在综合元分析中得到了验证（n=41,830）。

几个候选基因与孟德尔心肌病基因重叠，并参与心肌收缩和细胞粘附。RV多基因风险评分（PRSs）与DCM和CAD相关。这些发现极大地促进了研究人员对RV测量的遗传基础的理解。

据介绍，右心室（RV）结构和功能影响冠状动脉疾病(CAD)、扩张型心肌病(DCM)、肺动脉高压和心力衰竭的发病率和死亡率。对RV测量的遗传基础知之甚少。

附：英文原文

Title: Genome-wide association analysis reveals insights into the genetic architecture of right ventricular structure and function

Author: Aung, Nay, Vargas, Jose D., Yang, Chaojie, Fung, Kenneth, Sanghvi, Mihir M., Piechnik, Stefan K., Neubauer, Stefan, Manichaikul, Ani, Rotter, Jerome I., Taylor, Kent D., Lima, Joao A. C., Bluemke, David A., Kawut, Steven M., Petersen, Steffen E., Munroe, Patricia B.

Issue&Volume: 2022-06-13

Abstract: Right ventricular (RV) structure and function influence the morbidity and mortality from coronary artery disease (CAD), dilated cardiomyopathy (DCM), pulmonary hypertension and heart failure. Little is known about the genetic basis of RV measurements. Here we perform genome-wide association analyses of four clinically relevant RV phenotypes (RV end-diastolic volume, RV end-systolic volume, RV stroke volume, RV ejection fraction) from cardiovascular magnetic resonance images, using a state-of-the-art deep learning algorithm in 29,506 UK Biobank participants. We identify 25 unique loci associated with at least one RV phenotype at P<2.27 ×108, 17 of which are validated in a combined meta-analysis (n=41,830). Several candidate genes overlap with Mendelian cardiomyopathy genes and are involved in cardiac muscle contraction and cellular adhesion. The RV polygenic risk scores (PRSs) are associated with DCM and CAD. The findings substantially advance our understanding of the genetic underpinning of RV measurements.

DOI: 10.1038/s41588-022-01083-2

Source: https://www.nature.com/articles/s41588-022-01083-2