William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
National Institute for Health Research, Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, UK.
Nat Genet. 2022 Jun;54(6):783-791. doi: 10.1038/s41588-022-01083-2. Epub 2022 Jun 13.
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 ×10, 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.
右心室（RV）的结构和功能会影响冠心病（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。关于 RV 测量的遗传基础知之甚少。在这里，我们使用最先进的深度学习算法，对 29506 名英国生物库参与者的心血管磁共振图像中的四个临床相关 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。我们确定了 25 个与至少一种 RV 表型相关的独特基因座，这些基因座在 P < 2.27 ×10 时具有统计学意义，其中 17 个在合并的荟萃分析中得到了验证（n = 41830）。一些候选基因与孟德尔心肌病基因重叠，参与心肌收缩和细胞黏附。RV 多基因风险评分（PRS）与 DCM 和 CAD 相关。这些发现大大提高了我们对 RV 测量遗传基础的理解。
